Endocrinology Flashcards

Question

Protein hormones have specific receptors on target tissue plasma membranes, whereas steroids (which are lipid-soluble, and able to permeate all cells of the body) have?

Answer 1

......Specific receptors within the cytoplasm or nucleus.

Answer 2

A result of a decrease in plasma concentrations of the hormone. Termination of a hormone action can also occur as a result of internalization of the receptor-hormone complex through the process of endocytosis; the hormone is degraded by lysosomal enzymes, whereas the receptor can be recycled to the plasma membrane.

Answer 3

Receptor synthesis can be stimulated by a hormone that is different from the hormone that interacts with the receptor. Conversely, receptor numbers can decrease in conjunction with continued interaction of receptor and hormone. This often occurs when an agonist, which has great affinity for the receptor is administered or when amounts of hormone are pathologically elevated. The receptor numbers are down-regulated in this situation. The end result is that the animal becomes resistant to continued therapy with the hormone in question.

Answer 4

-Steroids interact directly with the cell nucleus through the formation of a complex with its cytosolic receptor, whereas protein hormones need a second messenger because they cannot enter the cell.

Answer 5

The interaction of receptor and steroid hormone results in activation of the subsequent comple translocation to the nucleus, where it interacts with specific sites on the chromatin. The result is the production of mRNA, which when translocated to the ribosomes directs synthesis of proteins that produce the desired biologic result.

Answer 6

The best-documented second messenger for protein hormones is cAMP, which is produced by the activation of an enzyme, adenyl cyclase, and the production of cAMP result in the phosphorylation of protein kinases, which are responsible for the biologic response.

Answer 7

Other secon messengers include cytosolic calcium, and its associated phosphodiesterase, calmodulin, as well as inositol triphosphate (IP3), and diacylglycerol.

Answer 8

An important action of IP3 is the stimulation of intracellular calcium release. An important response to diacylglycerol is the activation of phospholipase A, and the formation of arachidonic acid, which leads to the formation of members of the prostaglandin family of molecules.

Answer 9

The biologic response to a protein or peptide hormone-receptor interaction is more rapid than that to steroids; preexisting enzymes are activated, whereas the biologic response to steroid requires the synthesis of enzyme protein.

Answer 10

-Metabolism of steroids usually involves reduction of the molecule, followed by conjugation with sulfates and glucuronides, which increases the water solublility of the steroids, allowing them to be excreted in the urine. The liver is the main organ responsible for this process.

Answer 11

Metabolism of hormones is usually relative constant, and the concentration of a hormone usually reflect the other determinant of hormone activity; the rate of synthesis of the hormone, although situation which affect the rate of clearance of a hormone exists (e.g., decrease due to pregnancy or increase due to liver disease).

Answer 12

-The most important feedback control for hormones is the negative feedback system, in which increased hormone concentrations results in less production of the hormone by the endocrine organ, usually through an interaction with the hypothalamus or pituitary gland. This type of control system is not an all-or-none arrangement, because changes and adjustments are being made continuously in order to maintain an optimal concentration of hormone.

Answer 13

In the negative feedback system, an increase in secretion of hormone results in a decrease in tropic hormone secretion. It is also possible to have a negative feedback system in which an increase in a physiologic substance, such as glucose, causes an increase in a hormone; in this case; insulin, which plays an important role in glucose metabolism; turning the glucose concentration toward normal again.

Answer 14

-Endocrine secretory patterns can be influenced by factors such as sleep or light and can produce circadian (or diurnal) rhythms (hormone patterns change on an approximate 24 hour basis). Rhythmic changes in hormone patterns that occur at shorter intervals, often in the range of an hour, are called ultradian rhythms.

Answer 15

The 2 major controlling systems are the nervous and the endocrine systems. The interface between these systems occurs, for the most part, in the hypothalamus. The hypothalamus is an area of the diencepahlon that forms the floor of the third ventricle and includes the optic chiasma, tuber cinererum, mammillary bodies, and the median eminence. Often not included in this classification are the infundibulum and the neurohypophysis (stalk of the posterior lobe and the posterior lobe, respectively), although both tissues represent extensions of the hypothalamus into the pituitary gland.

Answer 16

The hypothalamus produces peptides and amines that influence the pituitary gland to produce 1) tropic hormones (e.g., corticotropin) which in turn influence the production of hormones (e.g., cortisol) by peripheral target endocrine tissues, or 2) hormones that directly cause a biologic effect in tissues (e.g., PRL). The hypothalamus is also the center for the control of a large number of autonomic nervous system control pathways.

Answer 17

The pituitary gland, or hypophysis cerebri, is compose of the adenohypophysis, the neurohypophysis, the pars intermedia, and the pars tuberalis.

Answer 18

-The neurohypophysis has cell bodies that originate in the hypothalamus (cell bodies there), with cell endings that secrete oxytocin and vasopressin.

Answer 19

Endocrine-secretory neurons differ from neurons involved in the transmission of neural signals in several ways; 1) neurosecretory neurons do not innervate other neurons, 2) the secretory product of neurosecretory neurons is secreted into the blood, and 3) the secretory product can act at distances greatly removed from the neuron. Also, in contrast to anterior pituitary hormones, which influence other tissues to produce hormones, posterior lobe hormones can directly cause the desired tissue response.

Answer 20

-Oxytocin and vasopressin (ADH); 2 important hormones produced by the neurohypophysis, are synthesized in cell bodies (due to depolarization caused by stimulation of neural afferents) within the hypothalamus (preprohormones) and are carried by axon flow to the posterior lobe. The pre-portion of the molecules are cleaved before the molecules are packed into granules and transported down the axon. The prohormone is cleaved to produce either oxytocin or vasopressin. Depolarization extends down the axon to the nerve terminal, where the secretory granules containing the hormone are stored and depolarization of the nerve cell membrane allows the influx of calcium ions, which initiates the release of hormone into the bloodstream through the process of exocytosis.

Answer 21

In dogs and cats arginine-vasopressin (AVP) or antidiuretic hormone (ADH) plays a vital role in water conservation.

Answer 22

-The main effects of oxytocin are on the contraction of smooth muscle (mammary gland and uterus); the effects of vasopressin are primarily on the conservation of water (antidiuresis) and secondarily on blood pressure = antidiuretic hormone (ADH).

Answer 23

Vasopressin is the most important hormone for the control of water balance: regulate body fluid homeostasis by affecting water reabsorption):Promotes reabsorption of solute-free water in the distal and collecting tubules of the kidney.

Answer 24

The protein aquaporin-2 is the major vasopressin regulating water channel in the kidneys. Within a few minutes, vasopressin increases water permeability of the collecting duct by stimulating the translocation of aquaporin-2 from an intracellular reservoir to the apical plasma membrane. The water molecule can move passively along an osmotic gradient from the distal and collecting tubules to the hypertonic renal medulla. Vasopressin also has a pressor effect, which involves the contraction of smooth muscle of the vascular system, and therefore has an effect on blood pressure.

Answer 25

Plasma osmolality (major determinant) controls the secretion of vasopressin through osmoreceptors located in the hypothalamus as well as through receptors located in esophageus and stomach that immediately sense water intake.

Answer 26

The regulation of the pressor effect of vasopressin- that is, through the blood volume- is achieved by increasing the number of action potentials in stretch receptors located in the atria. A decrease in blood volume activates the stretch receptors, which inhibit activity of neurons, vagal in origin, that inhibit the osmoreceptor cells, which are concentrated in the hypothalamus. Blood volume changes that decrease blood pressure also affect vasopressin release through activation of baroreceptors in the carotid sinus and aortic arch.

Answer 27

Cations, drugs, and hormones can influence the action of vasopressin, thereby causing polyuria. Calcium inhibits the adenylate cyclase response to vasopressin. Glucocorticoids also interfere with the action of vasopressin, although in dogs loss of reactivity of the osmoreceptor system also seems to contribute to corticosteroid induced PU. Even physiologic increases in cortisol inhibit basal vasopressin release in dogs.

Answer 28

Diabetes insipidus (DI) Refers to the passage of large quantities of dilute urine and is actually synonymous with polyuria. Disorder of water metabolism characterized by 3 primary findings: 1) dilute urine despite strong osmotic stimuli for vasopressin secretion, 2) absence of renal disease, and 3) a rise in urine osmolality following the administration of vasopressin.

Answer 29

It is caused by defective secretion of ADH (central DI; commonly seen in young adults) or by the inability of the renal tubule to respond to ADH (nephrogenic DI).

Answer 30

Deficiency of ADH can be absolute or relative lack of circulating ADH, and is classified as primary (idiopathic and congenital) or secondary. Secondary central DI usually results from head trauma (usually associated with fractures of the skull) or neoplasia (intracranial tumor). Metastatic, inflammatory, and parasitic lesions may also cause central DI. An increasingly common cause is pituitary surgery. Hypophysectomy may lead to retrograde degeneration of the hypothalamic neurons, and central DI may be permanent.

Answer 31

DI may also be classified into complete or partial central DI. Complete; little or no rise in urine osmolality, with increasing plasma osmolality. Partial DI: vasopressin is release with increasing plasma osmolality, but is subnormal in amount. In some cases this moderate vasopressin release only start at rather high plasma osmolality values; not only is the secretory capacity limited, but there is also a high setting of the osmoreceptor.

Answer 32

Major clinical signs of DI: profound PU/PD. PD: more than 100 ml/kg/day (normal 40-70 ml/kg/day), nocturia, and incontinence, usually of several months duration. Less consistent signs; weight loss (because these animals are constantly seeking water) and dehydration. Blood work usually normal. High plasma osmolality (>310 mOsm/L) in central or nephrogenic DI as a result of dehydration. Animals with primary PD often exhibit low plasma osmolality (

Answer 33

In DI, the urinalysis is unremarkable except for the finding of a persistently dilute urine (urine specific gravity 1,004 to 1.012). Diagnostic tests to confirm and differentiate central DI, neprhogenic DI, and psychogenic PD include the modified water deprivation test (Designed to determine if endogenous ADH is released in response to dehydration and if the kidneys can respond to ADH). Rule out more common causes of PU/PD first) or response to ADH supplementation.

Answer 34

Hypersecretion of vasopressin in the absence of osmotic or volumetric stimulation is called the syndrome of inappropriate ADH secretion. Neoplastic processes are often involved I this syndrome; ectopic tumors, often located in the lung, are the neoplasms most commonly involved.

Answer 35

Growth hormone (GH, also called somatotropin), prolactin (PRL) , thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and corticotropin.

Answer 36

the pars distalis, and the pars intermedia.

Answer 37

-Adenohypophyseal activity is controlled by hypothalamic-releasing hormones, which are released into the portal system, which in turn connects the median eminence of the hypothalamus and the anterior pituitary gland. Whereas neurons that compose the neurophyophysis are influenced directly by neural input within the hypothalamus, the imposition of a vascular system between the hypothalamus and the adenohypophysis requires a different type of control system. The hypothalamus produces regulatory of hypophysiotropic hormones, which are transported to and released within the median eminence (comparable with posterior lobe hormones). These regulatory hormones then pass via the portal venous system to the adenohypophysis, where they stimulate the release of the various anterior pituitary hormones.

Answer 38

Synthesis of adenohypophyseal regulatory hormones is controlled by both neural and hormonal inputs at the level of the hypothalamus. Some of the hypophyseal hormones have been found in other areas of the brain and extraneural sites, including the GI tract and the pancreas.

Answer 39

Thyrotropin-releasing hormone (TRH), Gonadotropin-releasing hormone (GnRH), Growth hormone-inhibiting hormone (GHIH), Growth hormone releasing hormone (GHRH), Corticotropin-releasing hormone (CRH), Prolactin-releasing factor (PRF), Prolactin-inhibiting hormone (or dopamine): PIH. Except for dopamine, all these hypophysiotropic hormones are peptides.

Answer 40

5 of the anterior pituitary hormones (FSH, LH, TSH, corticotropin, GH) are considered to be tropic; that is that their main effect is stimulation of hormone secretion by specific endocrine organs located peripheral to the pituitary gland).

Answer 41

The most important regulation of secretion of the protein hormones by the pars distalis is by negative feedback inhibition of the tropic pituitary hormone by interaction of the target organ hormone with the hypothalamus, as well as with the pituitary gland; long-loop feedback system.

Answer 42

PRL remains as the only pars distalis hormone for which negative feedback inhib has not been demonstrated through hormones produced by PRL-target tissues. E.g., cortisol is produced by the adrenal cortex as a result of corticotropin stimulation, and cortisol, in turn, has a negative feedback effect on corticotropin production at the level of the hypothalamus and the anterior pituitary gland. Short-loop feedback systems, anterior pituitary hormone, such as corticotropin, has a direct negative feedback inhibition of hormone secretion-in this case, corticotropin-releasing hormone secretion-within the hypothalamus.

Answer 43

Located at the level of the first or second tracheal ring. The gland is composed of 2 lobes lying on either side of the trachea, and connected by a narrow piece of tissue called the isthmus. The most important gland for metabolic regulation. Cells in the gland are formed in a circular arrangement called a follicle. The follicles are filled with a homogenous-staining substance called colloid, which is the main storage form of the thyroid hormones. Another important endocrine cell, the parafollicular, or C.cell, is located outside the follicles. This cell secretes calcitonin, a hormone important for the regulation of calcium.

Answer 44

-The thyroid hormones are iodine-containing amino acids, which are synthesized from 2 connected tyrosine molecules that contain 3 or 4 iodine molecules. 2 molecules are important for thyroid hormone synthesis; tyrosine and iodine.

Answer 45

Tyrosine is a part of a large molecule called thyroglobulin that is formed within the follicle cell and secreted into the lumen of the follicle. Iodine is converted to iodide in the intestinal tract and then transported to the thyroid, where the follicle cells effectively trap the iodide through an active transport process. This allows intracellular iodide concentrations to be 25 to 200 times higher than extracellular concentrations. As iodide passes through the apical wall of the cell, it attaches to the ring structures of the tyrosine molecules, which are part of the thyroglobulin amino acid sequence.

Answer 46

The tyrosyl ring can accommodate 2 iodide molecules; attachment of 1 iodide molecule; monoiodotyrosine. 2 molecules; diiodotyrosine. Coupling of 2 iodinated tyrosine molecules results in the formation of the main thyroid hormones; 2 diiodotyrosine molecules form tetraiodothyronine (T4), and 1 diiodotyrosine and 1 monoiodotyrosinemolecule form triiodothyronine (T3).

Answer 47

A key enzyme in the biosynthesis of thyroid hormones is thyroperoxidase (which works in cocert with an oxidant; hydrogen peroxide). Thyroid hormones are the only hormones containing a halide (i.e.,iodine). Thyroxiperoxidase catalyzes the iodnation of the tyrosyl residues of thyroxine-binding globulin (TBG) and the formation of T3 and T4.

Answer 48

All circulating T4, but only 20% of T3 is derived from the thyrpid gland. The majority of T3 is derived from extrathyroidal enzymatic 5’-deiodination of T4.

Answer 49

-Thyroid hormones are stored outside the cell and attached to thyroglobulin in the form of colloid. Once thyroid hormones are synthesized they remain in the extracellular acinar lumen until release. This is a unique storage arrangement for a hormone. It allows the thyroid gland to have a large reserve of hormone.

Answer 50

-The release of thyroid hormones involves transport of thyroglobulin with attached thyroid hormones into the cell, cleavage of the thyroid hormones from thyroxine-binding globulin, and release into the interstitial tissues.

Answer 51

In order for thyroid hormones to be released from the thyroid gland, thyroglobulin with its attached monoiodotyrosine, diiodotyrosine, T3, and T4 molecules must be translocated into the follicle cell, and the hormones must be cleaved from thyroglobulin. Key enzymes in this transfer are found in the lysosomes. On entering the cell, the TBG (thyroxine-binding globulin) molecules fuse with lysosomes, and lysosomal enzymes cleave both the iodinated tyrosine molecules and the iodinated thyrosines from the thyroglobulin molecules. The thyrosine are released through the basal cell membrane.

Answer 52

Monoiodotyrosine and diidotyrosine are deiodinated by an enzyme called iodotyrosine dehalogenase; and both the iodide and the remaining tyrosine molecules are recycled to form new hormone in association with thyroglobulin. Majority of T3 formation occurs outside the thyroid gland by deiodination of T4, and the highest conc of deiodinating enzymes are those of liver and kidneys, although muscle tissue produces more T3 on the basis of relative size.

Answer 53

-Thyroid hormones are transported in the plasma attached to plasma proteins. T4 is more highly bound to plasma protein than T3. Lipid-soluble hormones are transported in the vascular system through association with specific binding plasma proteins. There is considerable species variation in the proteins that bind thyroid hormones. The most important carrier protein for T4 and T3 is thyroid hormone-binding globulin (TBG). TBG not reported in cats. Albumin is also involved in the transport of thyroid hormones (not high affinity for T3, T4, but high concentration in the plasma). Most important carrier protein for T3, T4 in the absence of TBG. Third plasma protein which has a capacity intermediate the other 2; thyroxine-binding peralbumin: specific for T4. Also transthyretin, and apolipoproteins can bind to T4 and T3.

Answer 54

The amount of free thyroid hormone (free to interact with receptors on the cells of target tissues) is remarkably low; little less than 1% for T4 and slightly more than 1% for T3. The equilibrium between free and bound hormone is easily shifted because of physiologic or pharmacologic situations. Increase in estrogen (during pregnancy) cause increased synthesis of TBG by the liver with a consequent shift toward the bound form. Adjustments to maintain a normal amount of free hormone occur rapidly with a decline in the rate of metabolism or with stimulation of thyroid hormone production through the release of pituitary thyrotropin/thyroid-stimulating hormone (TSH). Thyroid hormone synthesis and secretion are regulated primarily by changes in the circulating conc of TSH.

Answer 55

-The main routes of metabolism of thyroid hormones are through deiodination (removal of iodide molecules) or the formation of glucuronides and sulfates via hepatic mechansims. Skeletal muscle, liver, and kidney tissues are important tissues involved in the catabolism of thyroid hormones through deiodination. Glucuronides and sulfates are formed mainly in the liver and kidneys.

Answer 56

Conjugation is less common than deiodination as a mean of metabolism of thyroid hormones. The deiodinated and conjugated forms of the thryonines are eliminated primarily in the urine, unmetabolized thyronines are excreted with feces through bile secretion. Degradation of the conjugated forms in the feces results in the production of iodide molecules, which are reabsorbed as part of a cycle called the enterohepatic cycle.

Answer 57

The half-life for T4 in dogs and cats is less than 24 h. Outer-ring deiodination of T4 produces T3, wheras inner-ring deiodination results in formation of biologically inactive reverse T3 (rT3). Deiodination is regulated by the relative activity of different deiodinase enzymes and is an important regulatory step in thyroid hormone metabolism. Thyroxine and T3 are both concentrated in the liver and secreted in the bile.

Answer 58

-Thyroid hormones are the primary factors for the control of basal metabolism of all tissues. Only unbound thyroid hormone enters cells to produce a biologic effect and a negative feedback effect on the pituitary and hypothalamus. T3 enters cells more rapidly, has a more rapid onse of action, and is 3-5 times more potent than T4.

Answer 59

Thyroid hormones are lipophilic; they can penetrate the cell membrane even though they are amino acids. Thyroid hormones bind to receptors in the nuclei, the hormone receptor complex binds to DNA and influences the expression of a variety of genes coding for regulatory enzymes. Although it is thought that thyroid hormones interact directly with the nucleus to initiate the transcription of messenger RNA (mRNA), the presence of T3 receptors has been reported on mitochondria.

Answer 60

Thyroid hormones have a wide variety of physiologic effects. Thyroid hormones increase the metabolic rate and oxygen consumption of most tissues, with the exception of the adult brain, testes, uterus, lymph nodes, spleen and anterior pituitary.

Answer 61

heat production calorigenic effect

Answer 62

One site of action of the calorigenic effect of thyroid hormones is within the mitochondrion. Thyroid hormones affect carbohydrate metabolism in several ways; increase intestinal glucose absorption and facilitate the movement of glucose in both fat and muscle, facilitate insulin-mediated glucose uptake by cells. Glycogen formation is facilitated by small amounts of thyroid hormones, however, glycogenolysis occurs after larger dosages.

Answer 63

Thyroid hormones in concert with growth hormone are essential for normal growth and development. This is accomplished, in part, by the enhancement of amino acid uptake by tissues and enzyme systems that are involved in protein synthesis.

Answer 64

Thyroid hormones affect all aspects of lipid metabolism, but the emphasis is placed on lipolysis. One particular effect of thyroid hormone is the tendency to reduce plasma cholesterol levels (increased uptake as well as increase the degradation both cholesterol and low-density lipoprotein). These effects on lipid metabolism are usually seen in pathophysiologic situations involving hypersecretion of thyroid hormone or in thyroid deficiency states in which hypercholesterolemia is a hallmark of thyroid deficiency. The effects of thyroid hormones on metabolic processes, including carbohydrate, protein, and lipid metabolism, are often described as catbolic.

Answer 65

The effects on the sympathetic nervous system are enhanced by the presence of thyroid hormones, potentially through thyroid stimulation of beta-adrenergic receptors in tissues that are targets for the catecholamines, such as epinephrine and norepinephrine (enhance the response to catecholamines). Important for normal development of tissues in the fetus and neonate; including CNS function.

Answer 66

Thyroid hormones have positive inotropic and chronotropic effects on the heart: Increase the heart rate and force of contraction, probably through their interaction with the catecholamines. Thyroid hormones increase the number and the affinity of beta-adrenergic receports, enhance the response to catecholamines, and increase the proportion of apha-myosin heavy chains. This interaction is caused by an increase in tissue responsiveness through the induction of catecholaminergic β receptors by thyroid hormones. Blood pressure is elevated because of increased systolic pressure, with no change in diastolic pressure; the end result is an increase in cardiac output. Accordingly; important for maintaining normal contractility of cardiac muscle, including the transmission of nerve impulses.

Answer 67

TSH, or thyrotropin, is the most important regulator of thyroid activity. It acts through the initiation of cAMP formation and the phosphorylation of protein kinases. TSH is regulated by thyroid hormones by way of negative feedback inhibition of the synthesis of thyrotropin–releasing hormone at the level of the hypothalamus and by inhibition of the activity of TSH at the level of the pituitary gland.

Answer 68

Thyroid hormones have catabolic effects on muscle andadipose tissue, stimulates erythropoiesis, and regulate both cholesterol synthesis and degradation. Thyroid hormones are also essential for the normal growth and development of the neurologic and skeletal system.

Answer 69

The ingestion of compounds that inhibit the uptake or the organic binding of iodine blocks the ability of the thyroid to secrete thyroid hormones, and causes goiter (struma?)

Answer 70

Hypothyroidism is most common in the dog. Hypothyroidism is the result of decreased production of thyroxine (T4) and triiodothyronine (T3) by the thyroid gland. Hypothyroidism may result from dysfunction of any part of the hypothalamic-pituitary-thyroid axis, but the usual etiology of primary hypothyroidism is lymphocytic thyroiditis or idiopatic thyroid atrophy.

Answer 71

Approximately 50% of of canine primary hypothyroidism is due to lympocytic thyroiditis. Grossly, the thyroid gland may appear normal or atrophic. There is multifocal or diffuse infiltration of the thyroid gland by lymphocytes, plasma cells and macrophages. Remaining follicles are small, and lymphocytes, macrophages, and degenerate follicular cells may be found within vacuolated colloid. As thyroiditis progresses, parenchyma is destroyed and replaced by fibrous connective tissu

Answer 72

Canine thyroiditis is believed to be immune mediated, but immunologic and molecular pathogenesis has not been well characterized. Antithyroiglobulin antibodies are present in 36-50% of hypothyroid dogs, but whether these antibodies occur secondary to follicular cell damage from infiltrating T cells or are directly involed in the pathogenesisi of thyroiditis is unclear.

Answer 73

In idiopathic follicular atrophy there is loss of thyroid parenchyma and replacement by adipose connective tissue. Degeneration of individual follicular cells occurs, with exfoliation of cells into the colloid. Because of the absence of fibrosis or inflammation it is unclear whether follicular atrophy is a distinct syndrome or the final result of thyroiditis.

Answer 74

Less commonly, hypothyroidism is caused by bilateral thyroid neoplasia or invasion of the thyroid by metastatic neoplasia. Dogs with thyroid neoplasia remain euthyroid until at least 75% of the thyroid parenchyma has been destroyed. Lymphocytic thyroididits has been identified as a risk factor for thyroid neoplasia. Reversible primary hypothyroidism may also result from treatment with high doses of potentiated sulfonamides

Answer 75

Congenital hypothyroidism (cretinism) may be caused by thyroid dysgenesis, dyshormonogenesis, T4 transport defects, goitrogens (goiter due to thyroid peroxidase deficiency (autosomal recessive trait in Toy Foxand Rat terriers), or, in rare cases; iodine deficiency. Secondary congenital hypothyroidism due to apparent isolated TSH or TRH deficiency has been reported (Giant Schnauzers and boxer).

Answer 76

Secondary hypothyroidism (deficiency of TSH) may be a secondary effect of pituitary tumors or malformation, radiation therapy, or ingestion of endogenous or exogenous glucocorticoids, and is rarely described in dogs.

Answer 77

Tertiary hypothyroidism can be acquired, as in the case of hypothalamic tumors, or congenital as a result of defective thyrotropin releasing hormone (TRH) or TRH receptor defects, but has not been described in dogs.

Answer 78

Iatrogenic causes include iodine treatment, adm of antithyroid drugs, and surgical thyroidectomy (however, rarely permanent due to accessory thyroid tissue).

Answer 79

Neuropathies. Myxedema coma; unusal finding in hypothyroid dogs, and is secondary to myxedematous fluid accumulations in the brain and severe hyponatremia.

Answer 80

Clinicopathologic findings: anemia from erythropoietin deficiency, decreased bone marrow activity and decreased iron and iron binding capacity are observed in about 25 to 30% of hypothyroid dogs.

Answer 81

Hypercholesterolemia in about 75% of affected dogs because of altered lipid metabolism, decreased fecal excretion of cholesterol, and decreased conversion of lipids to bile acids.

Answer 82

Hyponatremia; about 30% of dogs (due to an increase in total body water as a result of impaired renal excretion of water and by retention of water by hydrophilic deposits in tissues. An unusual clinicopathologic feature of hypothyroidism is increased serum creatinine phosphokinase levels, possibly as a result of hypothyroid myopathy.

Answer 83

Myxedema; rare: due to deposition of hyaluronic acid in the dermis.

Answer 84

Both the peripheral and central nervous systems may be affected. Diffuse peripheral neuropathy is the best documented neurologic manifestation. Subclinical myopathy also occurs. Dysfunction of multiple cranial nerves (facial, trigeminal, vestibulocochlear), sometimes in conjunction with abnormal gait and postural reactions. Seizures, disorientation and circling may occur due to severe hyperlipidemia or cerebral atherosclerosis. Hypothryoidism is a risk factor for atherosclerosis in dogs, likely because of hypercholesterolemia.Ocular abnormalities occurs.

Answer 85

Congenital hypothyroidism: Results in mental retardation and stunted disproportionate growth due to epiphyseal dysgenesis and delayed skeletal maturation. Normal at birth, but start to lag behind their litermates 3-8 weeks after birth. Mentally dull and have large, broad heads, short thick necks, short limbs, macroglossia, hypothermia, delayed dental eruption, ataxia, and abdominal distention. Large goiters are present due to iodination defects, such as in Toy Fox terriers and Rat tewrrriers. Dermatologic findings like in adults; delayed development of guard hairs, and soft fluffy haricoat. Even more clinical signs of disease. S 1754 Ettinger.

Answer 86

Polyendocrinopathies: May occur in association with other immune-mediated endorine disorders such as hypoadrenocorticism and diabetes mellitus. Hypothyroidism is a cause of insulin resistance in dogs. Hypothyroidism also causes an increase in serum fructosamine concentration due to decreased protein turnover, so fructosamine may not be a good indicator of glycemic control in dogs with both diabetes and hypothyroidism. Concurrent hypothyroidism may cause a poor clinical response to treatment in dogs with hypoadrenocorticism.

Answer 87

Clinicopathologic changes: Mild nonregenerative anemia, fasting hypercholesterolemia, hypertrigluceridemia mm.

Answer 88

Euthyroid sick syndrome due to concurrent illness is characterized by a decrease in serum total T4 and increase in reverse T3. In nonthyrpid illness, thyroid hormone conc usually decrease. Changes in hormone binding to serum carrier proteins (e.g decreased protein conc, reduced binding affinity, circul inhibitors of binding) or peripheral hormone distribution and metabolism, inhibition of TS secretion, and inhibition of thyroid hormone synthesis may occur. Cytokines decreases TT4 conc .

Answer 89

Drugs, such as glucocorticoids, phenylbutazone, salicylates,phenobarbital can also decrease serum basal TT4 conc. Theroretically, FT4 is not subject to spontaneous or drug-induced changes that occur with TT4, however, glucocorticoid decrease also FT4.

Answer 90

Nonthyroidal disease can affect endogenous TSH conc as mush as FT 4and TT4 conc.

Answer 91

ATAA: : antithyroglobulin autoantibodies test (ATAA): the presence of antithyroglobulin antibodies theoretically presages the onset of hypothyroidism in dogs with autoimmune thyroiditis. Identify hereditary thyroid disease before breeding. -All measurements abnormal: hypothyroid -2 of 3 are abnormal: secondary hypothyroidism (low FT4, low TSH) or early primary hypothyroidism (high TSH, low FT4) is possible. - If only 1 of 3 measurements are abnormal: reevaluation in 3-6 months should be performed.

Answer 92

Hyperthyroidism: Caused by adenomatous hyperplasia of the thyroid gland. Characterized by hypermetabolism. Activation of the sympathetic nervous system; hyperactivity, tachycardia, pupillary dilatation, behavioral changes. Long-standing hyperthyroidism leads to hypertrophic left chamber walls, high-output heart failure, and cachexia, which may lead to death.

Answer 93

Clinicopathologic features; erythrocytosis, excitement leukogram (neutrophilia, lymphocytosis) caused by increased circulating catecholamine concentrations. Increased catabolism of muscle tissue in hyperthyroid cats may result in increased levels of blood urea nitrogen (BUN) but not creatinine. Increased GFR. Potentially decreased urine specific gravity (polyuria). Increased metabolic rate results in liver hypermetabolism; serum activities of liver enzymes increase in 80-90% of hyperthyroid cats. Serum cholesterol decreases, not as a result of decreased synthesis, but rather as a result of increased hepatic clearance mediated by thyroid hormone excess.

Answer 94

Nonthyrpid illness (chronic renal failure) can result in spurious elevations of FT4. Measure TT4.

Answer 95

Functional adenomatous hyperplasia (or less frequently adenoma) of one or, more commonly, both (70% of cases) thyroid lobes is the most common abnormality associated with hyperthyroidism in cats. On histologic examination, the normal thyroid follicular architecture is replaced by one or more, well discernible foci of hyperplastic tissue that can form nodules with wide variation in follicular size and architecture both within and between individual nodules. Normal but compressed thyroid tissue is often found surrounding abnormal follicles. Thyroid carcinoma, by contrast, is rare, accounting for less than 2% of hyperthyroid cases.

Answer 96

Although the disorder and its pathologic lesions have by now been well described, the cause remains obscure. Siamese and Himalayan, and purebred cats are at decreased risk of developing hyperthyroidism. Cats fed almost entirely canned food have an increased risk of developing hyperthyroidism. Because of this dietary association, iodine has been implicated in the cause or progression of the disease. The iodine content of cat food is extremely variable and often up to 10 times the recommended level. It has been postulated that wide swings in daily iodine intake may somehow contribute to the development of thyroid disease.

Answer 97

Thyroid hormones are responsible for a wide variety of actions including the regulation of heat production, as well as carbohydrate, protein, and lipid metabolism. They also interact with the nervous system, increasing overall sympathetic drive. Consequently, almost any organ can be affected by hyperthyroidism and each altered system can cause a variety of clinical signs.

Answer 98

Weight loss is the most common feature of hyperthyroidism occurring in more than 80% of cats, resulting in overt cachexia in severe cases. This reflects the overall increase in metabolic rate, which may be accompanied by a mild elevation in body temperature or heat intolerance. Muscle weakness and muscle atrophy with fatiguability are occasionally described. The pathophysiology of muscle weakness is unclear but presumably is related to the thyrotoxicosis-associated weight loss. Severe muscle weakness (exhibited by ventriflexion of the neck) is rarely described and may result from hypokalemia occasionally reported in hyperthyroid cats.

Answer 99

Polyuria and polydipsia reportedly occur in less than 50% of hyperthyroid cats but can be marked in some. Various mechanisms may be responsible including concurrent primary renal disease, a common problem in aged cats. Other explanations include increased renal blood flow decreasing medullary solute concentration gradient, electrolyte abnormalities, and primary polydipsia because of a hypothalamic disturbance induced by thyroid hormone excess.

Answer 100

The systemic hypertension accompanying hyperthyroidism could be transmitted to glomeruli and, in the absence of autoregulation, intraglomerular and glomerular hypertension potentially results. These factors may contribute to glomerular sclerosis and progression of renal failure in cats. On the other hand, hyperthyroidism may prove beneficial in maintaining sustainable renal function in cats with preexisting renal disease. Overt renal dysfunction signs may be unmasked upon reversal of the hyperthyroid state, and it is this effect that appears to be of greatest concern when considering treatment of affected cats.

Answer 101

Approximately 50% are described as polyphagic. Despite the increased appetite, caloric intake is rarely adequate to compensate for increased expenditure and weight loss generally ensues. Up to 20% of hyperthyroid cats exhibit short periods of anorexia that alternate with longer periods of normal or increased appetite, although the reasons for this are unclear. Intermittent GI signs of vomiting and, less commonly, diarrhea (increased frequency or volume or steatorrhea) are frequently observed in hyperthyroid cats. Rapid overeating may contribute to vomiting, particularly in multicat households; however, direct stimulation of the chemoreceptor trigger zone is also possible. Intestinal hypermotility, excess fat intake, and a reversible reduction in pancreatic exocrine function all contribute to the diarrhea associated with hyperthyroidism in humans.

Answer 102

Cardiovascular signs are common in hyperthyroidism. They include tachycardia, systolic murmurs, a prominent apex beat, and, less commonly, arrhythmias. Hyperthyroidism is usually associated with a form of hypertrophic cardiomyopathy that can result in cardiac failure in the absence of any underlying myocardial abnormalities. Less commonly, a dilated form of cardiomyopathy with severe signs of CHF has been described. The exact mechanism for the cardiac abnormalities is unclear but appears to involve a combination of direct action of excess thyroid hormones on the heart, interactions between thyroid hormones and the sympathetic nervous system, and cardiac changes that compensate for altered peripheral tissue function.

Answer 103

In healthy cats the thyroid gland is divided into two separate lobes positioned just below the cricoid cartilage. Each lobe extends ventrally over the first five or six tracheal rings and neither is normally palpable. Enlargement of one or more thyroid lobes is detectable by palpation in more than 80% of cases. With progression of the disease and greater clinician experience, goiter may be detectable in more than 95% of cats. Thyroid lobes are loosely anchored to surrounding tissues and as they enlarge tend to migrate ventrally toward the thoracic inlet, occasionally entering the anterior mediastinum. Ectopic thyroid tissue, located anywhere from the base of the tongue to the base of the heart, can also be involved. Occasionally goiter is visible, but in most cases palpation is required. The presence of a cervical mass is not always synonymous with hyperthyroidism. Masses can be associated with lymph node enlargement or parathyroid hyperplasia and neoplasia. In addition, goiter may develop in cats without overt hyperthyroidism, although undoubtedly T4 secretion increases in many of these individuals with time necessitating careful and regular reexaminations.

Answer 104

Two separate studies have examined the effect of hyperthyroidism on circulating fructosamine concentration. In both studies, serum fructosamine concentration was significantly lower in hyperthyroid compared with healthy cats, presumably as a result of increased protein turnover. Importantly, as many as 50% of cats had values below the respective reference range. Caution is therefore advised in interpreting serum fructosamine concentration in hyperthyroid cats, particularly if concurrently diabetic. Approximately 50% of hyperthyroid cats have circulating cardiac troponin I concentrations within the detectable range, and these values decrease with successful induction of euthyroidism. Urinalysis is generally unremarkable. Bacterial urinary tract infections (UTIs) occur with a prevalence of 12%, similar to the prevalence in diabetic cats, but appear unrelated to low USG.

Answer 105

In cats, T4 rather than T3 is the main secretory product of the thyroid gland. However, T3 is three to five times more potent than T4. Most circulating T3 is produced from extrathyroidal 5′-deiodination of T4, and as a result T4 is often considered as a prohormone, and activation to T3 a step that is autoregulated by peripheral tissues. More than 99% of circulating T4 is protein bound, while the remainder is free and metabolically active. Overall control of thyroid function is mediated via the negative feedback effect of circulating T4 and T3 on thyrotropin-releasing hormone (TRH) from the hypothalamus and TSH from the anterior pituitary.

Answer 106

Circulating total T4 is preferable. Severe concurrent nonthyroidal illness may play a role in suppressing T3 concentration by inhibiting peripheral conversion of T4 to T3, as it does in humans, although this appears to be a less common phenomenon in cats.

Answer 107

Hyperthyroidism should not be excluded on the basis of finding a single reference range total T4 value.

Answer 108

Nonthyroidal illness is capable of suppressing circulating total T4 concentration in cats as in dogs. The degree of suppression is correlated to the severity rather than the type of illness. The mechanisms remain unclear but most likely involve changes in protein binding or metabolism rather than any effect on the hypothalamic-pituitary-thyroid axis. Similar suppression occurs in hyperthyroid cats with concurrent nonthyroidal illness.

Answer 109

Notably, when serum total T4 concentration is increased, the concentration of free T4 is disproportionately increased. This may be related in part to relative saturation of binding proteins by T4 and subnormal concentration of the principle binding proteins. In addition, serum-free T4 concentration remains increased in hyperthyroid patients with nonthyroidal illnesses when total T4 concentration is suppressed into the reference range. However, measurement of free T4 concentration offers no further diagnostic information. Identification of concurrent nonthyroidal illness, repeat total T4 analysis, or simultaneous free T4 and TSH measurements usually provides enough evidence to confidently diagnose hyperthyroidism.

Answer 110

Thyrotropin-releasing hormone response test In healthy cats, administration of TRH causes an increase in TSH and, in turn, thyroid hormone secretion. In hyperthyroidism, this pathway is less functional because of chronic TSH suppression from autonomous thyroid hormone production. A significant increase occurs in mean serum total T4 concentration after TRH administration in healthy and hyperthyroid cats and those with nonthyroidal illness. However, the percentage increase in total T4 is considerably less in the hyperthyroid cats compared with healthy cats and those with other diseases.

Answer 111

Triiodothyronine suppression test The T3 suppression test relies on the ability of administered liothyronine, through negative feedback, to decrease T4 production by the thyroid gland. In hyperthyroidism, because excess circulating thyroid hormone concentrations have already suppressed TSH production and secretion, additional T3 has minimal effect on T4 production. Therefore, serum total T4 concentration remains significantly higher after liothyronine administration in hyperthyroid compared with euthyroid (both healthy and sick) cats and the percentage decrease is consequently significantly lower. However, suppression of 50% or more is consistent with euthyroidism, whereas hyperthyroid cats rarely have values exceeding 35%. Although the T3 suppression test is a potential aid for confirming the diagnosis of hyperthyroidism, it has been suggested to be most useful in confirming euthyroidism and ruling out hyperthyroidism. Unlike the TRH response test, it is not associated with any adverse reactions.

Answer 112

Hyperthyroid cats usually exhibit increased thyroidal uptake of radioactive iodine (as 131I or 123I) or technetium-99m as pertechnetate (99mTc04 Values are significantly higher in hyperthyroid cats compared with healthy cats and correlate well with circulating thyroid hormone concentrations.

Answer 113

Treatment of hyperthyroidism is aimed at removing or destroying abnormally functioning thyroid tissue, pharmacologic inhibition of thyroid hormone synthesis and release, or amelioration of the influence of excess thyroid hormones on peripheral tissue. Surgical thyroidectomy and thyroid ablation using radioactive iodine are the only reasonable curative methods. Medical management is noncurative, so it is not recommended alone in the rare cases of functioning thyroid carcinoma.

Answer 114

The thioureylene antithyroid drugs include propylthiouracil, methimazole, and carbimazole. These drugs are actively concentrated by the thyroid gland and act as general inhibitors of thyroid peroxidase-catalyzed reactions including oxidation of iodide and iodination of tyrosyl residues in thyroglobulin. They also interfere with the coupling of iodotyrosines to iodothyronines via inhibition of thyroid peroxidase or by binding to and altering the structure of thyroglobulin, a reaction more sensitive to inhibition than the formation of iodotyrosines.

Answer 115

Methimazole and carbimazole have no effect on the underlying pathologic lesion in hyperthyroid cats. Thus over months to years of treatment, the thyroid nodule or nodules can continue to grow and enlarge.

Answer 116

Early in the course of therapy, mild hematologic complications of eosinophilia, lymphocytosis, and leukopenia (with a normal differential count but without apparent clinical effect) occur in up to 16% of cases treated with methimazole and only 5% of cases treated with carbimazole. More serious hematologic complications occur in less than 5% of cats treated with methimazole and include agranulocytosis and thrombocytopenia, either alone or concurrently, or more rarely, immune-mediated hemolytic anemia (usually occurring within the first 3 months of therapy).

Answer 117

Propranolol is a nonselective beta-adrenoceptor blocking agent and is therefore contraindicated in cats with asthma or preexisting uncontrolled overt CHF. Atenolol, as a selective beta-1 adrenoceptor blocking agent is more useful in some of these situations. Calcium ipodate, an oral cholecystographic contrast agent, is the only other drug that has been assessed in hyperthyroid cats. Its major effect is to acutely inhibit peripheral T4 to T3 conversion.

Answer 118

It is estimated that both thyroid lobes are affected in more than 70% of cases, thereby necessitating a bilateral thyroidectomy. Hypoparathyroidism resulting in hypocalcaemia is the most significant potential postoperative complication. Mild hypocalcaemia develops in most cats post bilateral thyroidectomy, but treatment is not necessary until clinical signs develop. Hypoparathyroidism is rarely permanent, and recovery of parathyroid function may occur days to months after surgery.

Answer 119

Administration of radioactive iodine as 131I is considered to be the safest, simplest, and most effective therapy for feline hyperthyroidism, emits both β-particles and γ-radiation. The β-particles cause more than 80% of the damage but are locally destructive, traveling a maximum of 2 mm with an average path length of 400 µm. There is, therefore, no significant damage to adjacent parathyroid tissue, atrophic thyroid tissue, or other cervical structures. The aim of therapy is to restore euthyroidism with the smallest possible single dose of radiation while avoiding the development of hypothyroidism.

Answer 120

Despite the potential adverse effect of hyperthyroidism on renal function, its presence can increase GFR, decrease serum creatinine concentration, and mask underlying renal disease. Decreased GFR, increased serum urea, and creatinine concentration and development of overt clinical signs of renal disease have all been reported after successful treatment of hyperthyroidism, regardless of therapeutic modality (methimazole, surgical thyroidectomy, or radioiodine). The decline in GFR is detectable within 1 month of treatment of the hyperthyroidism but remains stable for at least 6 months thereafter.

Answer 121

Thyroid tumors account for 1.2% to 3.75% of all tumors and approximately 10% to 15% of all head and neck neoplasms in the dogs. In pathologic studies, benign adenomas account for 30% to 50% of all thyroid tumors, but these are usually small focal lesions uncommonly detected during life. On the other hand, carcinomas, responsible for only 50% to 70% of all thyroid tumors diagnosed postmortem, account for up to 90% of those tumors detected antemortem. All thyroid masses detected during life should, therefore, be presumed malignant until proven otherwise. Hyperthyroidism occurs in approximately 10% to 20% of thyroid carcinomas but is unusual in the rare cases of detectable adenomas.

Answer 122

Growth hormone disorders; Acromegaly and Pituitary Dwarfism Like the other hormones of the pituitary anterior lobe, GH is secreted in rhythmic pulses and intervening troughs. Pituitary GH secretion is regulated mainly by the opposing actions of the stimulatory hypothalamic peptide GH-releasing hormone (GHRH) and the inhibitory hypothalamic peptide somatostatin. In the dog, circulating GH originates from the pituitary but may also be of mammary origin (progestin).

Answer 123

The effects of circulating GH can be divided into 2 main categories: rapid catabolic actions, and slow (long-lasting) hypertrophic actions.

Answer 124

The acute catabolic actions are mainly due to insulin antagonism and result in enhanced lipolysis, gluconeogenesis, and restricted glucose transport across the cell membrane. The net effect of these catabolic actions is promotion of hyperglycemia. The slow anabolic effects are mainly mediated via insulin-like growth factors (IGFs), which are produced by many different tissues, and in most of these tissues they have a local (paracrine or autocrine) growth-promoting factor. The main sources of circulating IGF-I are the liver and the kidneys.

Answer 125

The chemical structure of IGF-I has about 50% sequence similarity with insulin. In contrast to insulin, IGFs are bound to binding proteins (IGFBPs), and because of this; they have a prolonged half-life, which is consistent with their long-term growth promoting actions. IGFs are important determinants in the regulation of body size, by stimulating protein synthesis, chondrogenesis, and growth.

Answer 126

The separation of the 2 opposing biologic effects of GH is not as strict as indicated in the previous paragraph. GH probably exerts its growth-promoting effect not only via IGFs but also by a direct effect on the cells. GH may be the major determinant of body size. Juvenile hypersomatotropism in young dogs of large breeds; high GH release a longer period.

Answer 127

IGF-I exerts an inhibitory effect on GH release, by stimulating the release of somatostatin and by a direct inhibitory influence at the pituitary level. In addition, GH itself has a negative feedback effect at the hypothalamic level.

Answer 128

Acromegaly, or hypersomatotropism, is the condition resulting from chronic excessive GH secretion in the adult animal. Acromegaly is a syndrome of bony and soft tissue overgrowth and insulin resistance due to excessive GH secretion.

Answer 129

Canine acromegaly is an extremely rare disorder observed in middle-aged and elderly female dogs, either after endogenous progesterone (luthal phase of the estrus cycle) or after exogenous progestins (used for estrus prevention in intact female dogs); which give raise to excessive secretion of GH from mammary cells under the influence of progesterone. In addition, primary hypothyroidism is associated with elevated plasma conc of GH and IGH-I in dogs. Finally, in rare cases a pituitary somatotroph adenoma may cause acromegaly in the dog.

Answer 130

Acromegaly in cats, as in humans, is caused by a GH-secreting somatotroph adenoma of the anterior pituitary gland. Occurs in older (8-14 year-old) cats and more commonly in males. Progestins may also induce GH expression in mammary tissue in the cat, but in this species, the hormone does not seem to reach the systemic circulation. The most common reason why cats with acromegaly are seen by vets is because of (insulin-resistant) diabetes mellitus.

Answer 131

Clinical signs of uncontrolled diabetes mellitus are often observed as the first manifestations of acromegaly; therefore PD, PU, and polyphagia are the most common presenting signs. Net weight gain of lean body mass in animals suffering from uncontrolled diabetes mellitus is a key sign of acromegaly. Diabetic cats requiring large insulin dosages should be screened for acromegaly.

Answer 132

Clinical signs: Organomgaly, including renomegaly, hepatomegaly, and enlargement of endocrine organs, is also observed. Some dogs and cats show the classic enlargement of extremities, body size, jaw, tongue, pharynx, and forehead (some may present with dyspnea) Increase in muscle mass and growth segments of the acral segments of the body; paws, chin, and skull. Thick skin folds (especially in the neck) and wide interdental spaces. Prolonged GH exess also leads to generalized visceromegaly resulting in abdominal enlargement. Cardiomegaly (hypertrophic chambers) and CHF develop late in the course of the disease; causing dyspnea.

Answer 133

The pituitary adenoma causing acromegaly in cats may become rather large in cats and may therefore result in neurologic signs. Some cats may have proliferative changes affecting joints, leading to progressive leading to progressive degenerative arthropathy and lameness.

Answer 134

Laboratory abnormalities: Impairments in glucose tolerance and insulin resistance that result in diabetes mellitus observed in all cats and most dogs with acromegaly. Very high insulin conc. Ketosis is rare in acromegaly animals. Severe insulin resistance (insulin requirement > 20U/cat/day) and hyperglycemia in cats; suspect acromegaly. Azotemia is sign occurring late. Polyuria is usually without glucosuria, but manifest diabetes mellitus can develop due to insulin resistance. Hypercholesterolemia and mild increase in serum activities of liver enzymes are attributed to the diabetic state (increase liver enzymes due in part to the intrinsic glucocorticoid activity of progestins). Hyperphosphatemia without azotemia is also a common clinicopathologic finding, perhaps as a result of GH stimulated bone growth. Persistent proteinuria; probably due to systemic hypertension and glomerulosclerosis.

Answer 135

A definitive diagnosis of acromegaly; Documentation of increased plasma G or somatomedin C conc. Cushing’s syndrome should be ruled out before measurement of GH. CT of the pituitary region. CT findings, coupled with the exclusion of other disorders that cause insulin resistance (hyperthyroidism, hyperadrenocorticism) in cats that exhibit clinical signs of acromegaly, should lead the clinician to the diagnosis of acromegaly. Sometimes feline acromegaly coexists with pituitary-dependent hypercortisolism.

Answer 136

Pituitary dwarfism

Answer 137

Any defect in pituitary gland organogenesis may result in isolated or combined pituitary hormone deficiency.

Answer 138

Clinical syndromes of (GH) somatotropin deficiency include pituitary dwarfism in the dog. Pituitary dwarfism results from destruction of the pituitary gland via a neoplastic, degenerative, or anomalous process.

Answer 139

Including TSH, ACTH, LH, FSH, and GH.

Answer 140

German shepherd dogs and Saarloos Wolfhpund dwarfs have a combined deficiency of GH, TSH, and prolactin together with impaired release of gonadotropins, but ACTH secretion is preserved in these animals.

Answer 141

Congenital GH deficiency is most common in German Shepherd dogs aged 2 to 6 months. Inherited as a simple autosomal recessive trait, and occurs most commonly as a result of cystic Rathke’s pouch; pressure atrophy of the pituitary anterior lobe occurs by the cyst formation. However, this is probably not the primary cause. Presumably, the disorder is caused by a primary failure of differentiation of the craniopharyngela ectorderm in normal tropic-hormone-secreting pituitary cells.

Answer 142

Poor growth, and retention of lanugo or secondary hairs, and lack of primary or guard hairs. Initially lively and alert, later; mental retardation (difficulty in house training) probably due to hypothyroidism and impaired renal function. Cryptorchidism alt persistent anestrus (impaired gonadotropin release). Increased creatinine conc.

Answer 143

Diagnosis is made by measuring serum growth hormone concentrations or serum somatomedin C (IGF-1). Usually a subnormal response to exogenous TSH and ACTH stimulation tests; furthermore, endogenous TSH and ACTH are decreased in affected dogs as a result of panhypopituitarism.

Answer 144

The Adrenal Glands 2 bilaterally symmetric endocrine organs located just anterior to the kidneys. Each gland is divided into 2 separate entities of different embryonic origins: a medulla and a cortex. The medulla produces amines such as norepinephrine and epinephrine. The cortex produces steroid hormones such as cortisol, corticosterone, sex steroids (androgens), and aldosterone.

Answer 145

Adrenal steroids are derived from cholesterol, and all contain the CPPP nucleus.

Answer 146

Both sets of hormones produced in the adrenal glands are important for adaption to adverse environmental conditions (i.e., stress). The major secretory products of the adrenal glands are cortisol, aldosterone, and the androgens dehydroepiandrosterone and androstenedione.

Answer 147

Other hormones such as progesterone and 17α-hydroxyprogesterone are synthesized in the adrenals, but in normal animals only small amounts are secreted into the systemic circulation. Adrenal derived androgens serve as substrates for synthesis of estrogen and testosterone in peripheral tissue.

Answer 148

The adrenal cortex: 3 zones: the outer zone: zona glomerulosa; which secretes mineralocorticoids (such as aldosterone by the enzyme aldosterone synthase), and the middle zone; zona fasciculate and the inner zone; zona reticularis; which secrete glucocorticoids and sex steroids (androgens).

Answer 149

All the cells of the adrenal cortex have intracellular feature characteristic of steroid hormone synthesis; an abundance of lipid droplets (containing cholesterol esters), mitochondria, and smooth endoplasmic reticulum.

Answer 150

Two major steroid hormones produced in the adrenal cortex: The mineralocorticoids plays an important role in electrolyte balance, and as a result, are important in the regulation of blood pressure. The major mineralocorticoid is aldosterone. The glucocorticoids are important in the regulation of all aspects of metabolism, either directly or through an interaction with other hormones. The major glucocorticoid is cortisol.

Answer 151

Synthesis and secretion of cortisol by the adrenal glands are regulated by the hypothalamic pituitary adrenal axis. Corticotropin-releasing hormone (CRH) secreting neurons in the hypothalamus have axons that terminate in the anterior pituitary. CRH stimulates secretion of ACTH from the pituitary gland. ACTH is released into the blood, attaches to receptors in the adrenal corted, and stimulates synthesis and secretion of cortisol. As the plasma cortisol conc rises, it inhibits CRH and ACTH release from the hypothalamus and pituitary by negative feedback. Increased ACTH conc also inhibits CRH release from the hypothalamus. ACTH release in normal animals is episodic.

Answer 152

Factors that stimulate CRH release include stress, hypoglycemia, and physical exercise.

Answer 153

Adrenal corticoids are synthesized from cholesterol; the critical difference in the activity of these corticoids is related to the hydroxyl group on C-17 of glucocorticoids.

Answer 154

Cholesterol is readily available to the steroid-synthesizing cells, because it is stored in large quantities in ester form within lipid droplets in these cells. One of the initial steps in steroid formation is the hydrolysis of the ester. The first step in steroid synthesis involves an enzyme that cleaves the carbon chain from the steroid molecule, leaving a C-21 steroid known as pregnenolone. The synthesis of all steroid hormones, regardless of their form, utilizes pregnenolone in the synthetic pathway.

Answer 155

Corticosterone, the immediate precursor to aldosterone, is a relatively important glucocorticoid in animals, although its potency is less than that of cortisol. Although the amount of sex steroids (androgens and estrogens) produced by the adrenal cortex under normal conditions is low, significant amounts can be synthesized under pathologic conditions.

Answer 156

-Adrenocortical hormones are carried in plasma in association with specific binding globulins (corticosteroid-binding globulin (transcortin)).

Answer 157

Steroid hormones are lipids, and depend on binding to plasma proteins for transport in the blood. Of the cortisol carried in plasma; 75% is bound to transcortin, and 15% to albumin, leaving 10% in the unbound, or free, state (in comparison; less than 0.1% of T4 is free). Accordingly, total concentration not only reflect secretion rate, but can also be influenced by the amount of glucocorticoid-binding plasma proteins (of which the amount can be influenced by physiologic or pathophysiologic states; liver disease; lower conc of transcortin, pregnancy; increased liver synthesis of transcortin). The transport of aldosterone is mainly associated with albumin (50%) and only 10% is associated with transcortin, leaving 40% in the free state.

Answer 158

-The metabolism of adrenocortical hormones involves the reduction of double bonds and conjugation of the steroids to glucuronides and sulfates (occurs in the liver); thereby reducing the biologic potency and render them water-soluble for passage in the urine..

Answer 159

The clearance half-life of cortisol is about 60 min, and that of aldosterone is about 20 minutes (difference due to observed difference in protein binding within plasma). Reduction of double bonds and ketone configuration; thereby reducing the biologic activity of the molecules.

Answer 160

-One of the most important functions of glucocorticoids is control of metabolism and, in particular, the stimulation of hepatic gluconeogenesis. Glucocorticoids have a variety of effects that make them crucial to normal homeostasis; stimulate hepatic gluconeogenesis, and glycogenesis, and enhance protein and fat catabolism. They have a permissive action on many metabolic reactions such as lipolysis and calorigenesis, and they are important in maintaining normal blood pressure and counteracting the effects of stress.

Answer 161

The lipophilic steroid hormones can penetrate the cell membrane and interact in the cytoplasm with specific cytosolic receptors. This complex is transferred to the nucleus with a resultant transcription of certain genes and the synthesis of specific proteins that affect the biologic action of the adrenal hormones.

Answer 162

Although cortisol is the dominant corticoid hormone, it also has mineralocorticoid effects, although at a reduced potency. Some overlap exist between the adrenocortical hormone activity.

Answer 163

Stimulation of hepatic gluconeogenesis; involves the conversion of amino acids to carbohydrates: the net result is an increase in hepatic glycogen and a tendency to increase blood glucose levels. These effects of glycogen metabolism are observed mainly in animals that suffer from excessive glucocorticoid secretion (hypeadrenocorticism) or that have an insulin deficiency.

Answer 164

The effect of glucocorticoids on carbohydrate metabolism is permissive; their presence is required for the gluconeogenic and glycogenolytic actions of glucagon and epinephrine, respectively.

Answer 165

Whereas glucocorticoids and insulin have similar effects on liver glycogen metabolism, their effect on the peripheral use of glucose are different. Glucocorticoids inhibit glucose uptake and metabolism in the peripheral tissues, particularly in the muscle and adipose cells= anti-insulin effect.

Answer 166

Steroid diabetes: Chronic adm of glucocorticoids can lead to development of steroid diabetes because of the hyperglycemic effect produced at the level of the liver, whereby use of glucose decreases in the peripheral tissues because of insulin antagonism.

Answer 167

The direct effect of glucocorticoids on fat metabolism tend to be complex, the direct effect on adipose tissue is to increase the rate of lipolysis and to redistribute fat into the liber and abdomen. Fat redistribution can lead to the classic “potbelly” appearance seen in individuals affected by hyperadrenocorticism.

Answer 168

Protein synthesis is inhibited by glucocorticoids, whereas protein catabolism is enhanced; releasing amino acids; thereby supporting gluconeogenesis. 2 tissues; cardiac and brain; are spared from this effect of glucocorticoids on protein catabolism.

Answer 169

Chronic adm of glucocorticoids; muscle wasting and weakness of bone. Mobilization and incorporation of amino acids into glycogen: increase in urinary excretion of nitrogen, and a negative nitrogen balance.

Answer 170

Glucocorticoids play a role in water diuresis (enhancement of water excretion): Glucocorticoids inhibit vasopressin activity in the distal tubule, but the most important effect is to increase the GFR. See tabl 33-3: effects of glucocorticoids.

Answer 171

-Corticotropin (tropic hormone) is the pituitary hormone that regulates glucocorticoid synthesis by the adrenal cortex by a negative feedback system. Glucocorticoids inhibit the release of hypothalamic corticotropin-releasing hormone, an this is turn, results in decreased corticotropin secretion by the pituitary gland. There is some evidence that glucocorticoids also have a negative feedback effect at the level of the pituitary gland. Cortisol has more potent negative feedback effects than does corticosterone, the former having more potent glucocorticoids effect than the latter.

Answer 172

Circadian rhythm: conc of glucocorticoids are lowest late at night and highest in the early morning hours. Stress; conc of cortisol increase rapidly to reach, within minutes, values that are several fold higher than normal. Glucocorticoid response is proportional to severity of stress, and the effect is mediated through CNS.

Answer 173

One of the most important clinical uses of glucocorticoids is the suppression of the inflammatory response; including prevention of capillary dilatation, extravasation of fluid into tissue spaces, leukocyte migration, fibrin deposition, and connective tissue synthesis.

Answer 174

Glucocorticoids inhibit the synthesis of inflammatory mediators, such as prostaglandins, thromboxanes, and leukotrienes, which arise as a result of arachidonic acid metabolism. This effect is mediated through the stabilization of lysosomal membranes and the prevention of phospholipase A2 activation.

Answer 175

Glucocorticoids are also used to inhibit allergic reactions through the inhibition of the release of certain biogenic amines, such as histamine from the granules of mast cells.

Answer 176

Hyperadrenocorticism (Cushing’s syndrome) May be caused by a pituitary tumor, pituitary hyperplasia, adrenal tumors, adrenal hyperplasia, or nonendocrine tumors (usually of the lung) or it may be iatrogenic.

Answer 177

Approx 85% of dogs; pituitary gland dependent disease, 15% adrenal tumors. (cats usually pituitary in origin). Uncommon clinical signs; hypertension, CHF, bronchial calcification, pulmonary thromboembolism, polyneutropathy, polymyopathy, pseudomyotonia, behavioral changes, and blindness, testicular atrophy, prostamegaly in castrated dogs, cliteral hypertrophy, perianal adenoma in females or castrated males.

Answer 178

Hypercortisolemia may lead to increased collagenase activity; leading to nonhealing corneal ulceration and bilateral cranial cruciate rupture (small dogs). Serum chemistry abnormalities: increased ALAT, ALP, hypercholesterolemia, hyperglycemia, and decreased BUN. Hemogram: often evidence of erythroid regeneration (nucleated red blood cells) and a classic “stress leukogram”. Basophilia is occasionally observed. Urinalysis: UTI without pyuria. Proteinuria resulting from glomerulosclerosis is also common. Decreased urine specific gravity, and may be hyposthenuric.

Answer 179

Hyperadrenocorticism (Cushing’s syndrome): Often also affected thyroid status: decreases in TT4 and TT3 (caused by euthyroid sick syndrome), and 2) a response to TSH stimulation that is attenuated as a result of overcrowding of pituitary thyrotrophs by adrenocorticotrophs.

Answer 180

Overt diabetes mellitus may result from the insulin antagonism caused by hypercortisolemia in about 15% of dogs with hyperadrenocorticism and about 85% of cats with hyperadrenocortisism. Conversely, hyperadrenocorticism can be a cause of insulin resistance and poor glycemic control in diabetic animals.

Answer 181

The eponym Cushing's syndrome is an “umbrella term” referring to the constellation of clinical and chemical abnormalities that result from chronic exposure to excessive concentrations of glucocorticoids. The eponym Cushing's disease is more specific and applies to individuals with Cushing's syndrome in which hypercortisolism occurs secondary to inappropriate excessive secretion of ACTH by the pituitary—that is, pituitary-dependent hyperadrenocorticism (PDH). As in humans, canine HAC also has various pathophysiologic origins, but all have that common denominator: chronic excesses in systemic cortisol.

Answer 182

The main three types of HAC are the result of excessive secretion of ACTH, a functional adrenal tumor, and iatrogenic causes.

Answer 183

The most common cause of an increased ACTH concentration is PDH resulting from pituitary tumors that synthesize and secrete excessive amounts of ACTH with secondary adrenocortical hyperplasia. (Rather than a primary pituitary disease, a hypothalamic disorder causing secondary pituitary hyperplasia is an extremely rare cause of HAC in people and has not yet been documented in dogs or cats. Finally, ectopic (nonpituitary) production of excessive amounts of ACTH is a well-known cause of HAC in humans, but the disorder has only been described in a few dogs and is quite rare).

Answer 184

Functional adrenocortical carcinoma or adenoma that autonomously produces excessive amounts of cortisol.

Answer 185

Excessive ACTH administration (extremely rare) or excessive glucocorticoid medication (quite common).

Answer 186

Neurotransmitters from the central nervous system modulate the release of hypophysiotropic hormones in the hypothalamus, such as corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). The hypothalamo-hypophyseal portal system carries the CRH to the anterior lobe of the pituitary, where it stimulates corticotropes to secrete ACTH.

Answer 187

In contrast to humans, the adenohypophysis of dogs and cats has a pars distalis and a distinct pars intermedia. The processing of POMC and the regulation of ACTH secretion differ between these two parts. Results of a study in dogs suggest that the pars intermedia may contribute to circulating ACTH concentrations.

Answer 188

In dogs, ACTH is secreted in a pulsatile manner with 6 to 12 daily peaks, but diurnal rhythms have not been detected. Secretion of ACTH is regulated by episodic CRH secretion, response to stress, feedback inhibition by cortisol, and immunologic factors. Physical, emotional, and chemical stressors such as pain, trauma, hypoxia, acute hypoglycemia, cold exposure, surgery, and pyrogens can stimulate ACTH and cortisol secretion.

Answer 189

The adrenal cortex has three histologically defined zones: the outer zona glomerulosa, the middle zona fasciculata, and the inner zona reticularis. Most of the enzymes involved in the synthesis of adrenal steroids belong to the family of cytochrome P450 oxygenases. Based upon the enzymatic differences between the zona glomerulosa and the inner two zones, the adrenal cortex functions as two separate units, each with distinct regulation and secretory products.

Answer 190

The outer zona glomerulosa produces mineralocorticoid (primarily aldosterone) and is deficient in 17-alpha-hydroxylase activity, which renders this zone incapable of synthesizing cortisol or androgens. In contrast, only cells in the zona glomerulosa contain the enzymes necessary for dehydrogenation of 18-hydroxycorticosterone to synthesize aldosterone.

Answer 191

Although ACTH stimulates aldosterone synthesis, it is regulated primarily by the renin-angiotensin system and serum potassium concentrations.

Answer 192

The middle zona fasciculata, the thickest of the three adrenocortical layers, functions as a unit with the narrow, inner zona reticularis; these are the two zones from which cortisol and androgens are produced. Only cells in these two layers of the adrenal cortex have 17-alpha-hydroxylase activity and can synthesize 17-alpha-hydroxypregnenolone and 17-alpha-hydroxyprogesterone, precursors of cortisol and adrenal androgens.

Answer 193

These zones are regulated primarily by ACTH. Delivery of ACTH to the adrenal cortex leads to a rapid synthesis and secretion of cortisol, primarily, and androgens. Plasma concentrations of these hormones increase within minutes. Chronic ACTH stimulation leads to adrenocortical hyperplasia and hypertrophy. Conversely, ACTH deficiency results in decreased steroidogenesis and is accompanied by adrenocortical atrophy and decreased weight of the adrenal gland.

Answer 194

Of dogs with naturally occurring HAC, 80% to 85% have PDH; that is, excessive secretion of ACTH by the pituitary, causing bilateral adrenal hyperplasia and excessive secretion of glucocorticoids. More than 90% of dogs with PDH have a pituitary tumor. Pituitary tumors may arise from the pars distalis or from the pars intermedia. In about 70% of dogs with PDH, the tumors originate in the pars distalis. About 30% of pituitary tumors arise either from the A cells or the B cells of the pars intermedia. The pars intermedia is under regulation by CRH, like the pars distalis. However, the relatively avascular pars intermedia is innervated and mainly controlled by dopaminergic and serotonin fibers from the brain.

Answer 195

Because most corticotrophs of the pars intermedia lack glucocorticoid receptors and extensive tumors appear to be resistant to glucocorticoids, tumors originating in the pars intermedia may grow larger than those in the pars distalis. However, it has also been stated that pituitary tumors do not always maintain the characteristics of the cells of origin and that PDH cannot be simply divided into either pars distalis or pars intermedia type by plasma α-MSH levels or dexamethasone resistance.[

Answer 196

Functioning pituitary carcinoma has been reported as a cause of PDH in dogs, although rare. Pituitary hyperplasia has also been mentioned as a cause of PDH in dogs; however, there is controversy about whether primary pituitary hyperplasia is a cause of PDH or if these dogs actually had a small microadenoma missed during histologic examination. Molecular studies have found that nearly all corticotroph adenomas are monoclonal, suggesting that ACTH hypersecretion arises from a naturally developing pituitary adenoma and that the resulting hypercortisolism suppresses the normal hypothalamic-pituitary axis and CRH release, thereby abolishing hypothalamic regulation of ACTH and cortisol.

Answer 197

Adrenocortical adenomas and adenocarcinomas can secrete excessive amounts of cortisol independent of pituitary control. Among dogs with naturally occurring HAC, 15% to 20% have an adrenal tumor. In these dogs, hypercortisolemia will suppress hypothalamic CRH and circulating plasma ACTH concentrations. The result of this chronic negative feedback is cortical atrophy of the uninvolved adrenal and atrophy of normal cells in the involved adrenal.

Answer 198

Cortisol secretion by functional adrenocortical tumors (FATs) is episodic and random. Most of these tumors appear to retain ACTH receptors because they respond to exogenous administration of ACTH by synthesizing and secreting cortisol. However, because pituitary secretion of ACTH is chronically suppressed, these tumors are typically unresponsive to manipulation of the hypothalamic-pituitary axis with pharmacologic agents such as dexamethasone.

Answer 199

There have been no consistent clinical or biochemical features that aid in distinguishing dogs or cats with functioning adrenal adenomas from those with adrenal carcinomas. The only clinical characteristic considered somewhat consistent is tumor size inasmuch as adrenocortical carcinomas tend to be larger than adenomas. Dogs with an adrenal diameter greater than 2 cm are more likely to have a carcinoma. Histologic differentiation between benign and malignant tumors can be difficult, and it is straightforward only when capsular or vascular invasion by the tumor has occurred. In some cases adrenocortical tumors that initially had been diagnosed as benign turned out to be malignant when metastases were discovered later. Usually a unilateral, solitary adrenal mass is seen, although less commonly bilateral tumors have also been described. Also, it is possible for a dog to have both a cortisol-secreting adrenal tumor together with a pheochromocytoma arising in the contralateral adrenal gland.

Answer 200

Adrenocortical Nodular Hyperplasia Dogs with PDH usually develop symmetrical bilateral adrenal hyperplasia. However, in some dogs, long-standing ACTH hypersecretion may result in nodular adrenal enlargement. In these cases, one or both adrenal glands are enlarged and may have one or several nodules of varying size in the adrenal cortex. Over time, these nodules may become autonomous or semiautonomous, making the distinction from bilateral adrenocortical adenomas difficult.

Answer 201

Ectopic ACTH Secretion from ex small cell lung carcinoma is seen in people. Also a possibility in dogs

Answer 202

The clinical signs and laboratory results in dogs with HAC are largely attributable to chronic glucocorticoid excess, although rarely, dogs with Cushing's disease have overproduction of other adrenocortical hormones (mineralocorticoids and/or sex hormones). In a few dogs, signs occur due to tumor growth, local invasion of tumors, or metastases.

Answer 203

The combined gluconeogenic, immune-suppressive, antiinflammatory, protein catabolic, and lipolytic effects of glucocorticoids on various organ systems.

Answer 204

The classical historical findings include polydipsia, polyuria, polyphagia, weight gain, muscle weakness, panting, and hair loss.

Answer 205

Attributed to increasing glomerular filtration rate and renal blood flow and inhibition of the antidiuretic hormone (ADH) action at the tubular levels. These dogs often exhibit a positive response to administration of natural or synthetic antidiuretic hormone, with a dramatic reduction in urine output and water intake, suggesting cortisol interference with release of antidiuretic hormone as an explanation for PU/PD.

Answer 206

Many dogs with HAC develop urinary tract infection (UTI) attributed to the immunosuppressive effects of cortisol excess. However, the typical signs of pollakiuria, hematuria, and stranguria may be minimal in some dogs as a result of the antiinflammatory action of cortisol. Additional and complimentary causes for UTI in HAC dogs are their low urine specific gravity, which is less bacteriocidal, and urine retention that occurs as house-broken dogs, producing huge volumes of urine, attempt to avoid urinating indoors. Many such dogs develop a degree of bladder atonicity. Glomerulopathy and associated proteinuria may occur.

Answer 207

Increased appetite is assumed to be a direct result of glucocorticoid excess in dogs. Excellent appetite or polyphagia is present in most HAC dogs. Some of these dogs have weight gain, but a larger percent appear to have gained weight due to their pot-bellied appearance. The pot belly is secondary to weakness of the abdominal musculature coupled with increased weight of abdominal content (hepatomegaly and large bladder together with fat redistribution to the abdominal mesentery). Muscle weakness is quite common, resulting from muscle wasting secondary to the catabolic effects of glucocorticoids. Infrequently, muscle weakness is so profound that dogs may not be capable of rising, may have difficulty standing, and may develop decubital ulcers.

Answer 208

Approximately 5% of dogs with HAC develop diabetes mellitus and these dogs might have weight loss. The hallmark of steroid-induced diabetes is the development of insulin resistance, defined clinically as persistent hyperglycemia despite insulin doses of >2 U/kg/administration. Cortisol antagonizes the actions of insulin by interfering with its action at the cellular level (receptor and postreceptor defects).

Answer 209

Excessive panting is also common and is attributed to decreased pulmonary compliance, respiratory muscle weakness, pulmonary hypertension, or the direct effects of cortisol on the respiratory center. Signs are further exaggerated by the stress of excitement or exercise.

Answer 210

In people, a condition called the “pickwickian syndrome” is characterized by marked obesity, alveolar hypoventilation, cyanosis, secondary erythrocytosis, and heart failure. Changes consistent with this syndrome are common in dogs with HAC. Pulmonary thromboembolic disease, a rare complication of HAC, can also cause moderate to severe respiratory distress.

Answer 211

Radiologic evidence of pulmonary mineralization is common in dogs with HAC. Changes in the pulmonary interstitial connective tissue induced by persistent excesses in plasma cortisol may result in dystrophic mineralization, causing a diffusion impairment to blood oxygenation.. Mineralization, therefore, may contribute to hypoxemia in some dogs with PDH.

Answer 212

Lethargy is the most common disturbance of central nervous system and may be associated with high concentrations of ACTH or the effects of excessive cortisol on cerebral enzymes and neurotransmitter synthesis. Other neurologic signs such us circling, seizures, behavior change, and depression may be caused by the compressive effects of a large, expanding pituitary tumor. Decreased appetite and weight loss can also occur in dogs with pituitary macroadenomas. Relatively infrequently, dogs with Cushing's syndrome have unilateral or bilateral facial nerve paralysis. The cause of facial nerve paralysis in dogs with HAC is not clear.

Answer 213

Hair loss is a common owner concern in dogs with HAC. The alopecia is truncal and bilaterally symmetric. The thin skin and the suppressed immune system predispose dogs with HAC to pyoderma. Skin infections develop in approximately half of the dogs with HAC.

Answer 214

Calcinosis cutis is an uncommon but characteristic dermatologic sign in dogs with HAC. The mechanisms of this process are not completely understood, but they involve phase transformation of calcium and phosphate ions from solution into crystalline aggregate with deposition in matrices of dermal collagen and elastin.

Answer 215

High circulating cortisol concentrations negatively feedback to the pituitary gland, decreasing FSH and LH plasma concentrations. Intact male dogs with HAC usually have bilaterally small, soft, spongy testicles. The female dog with HAC commonly ceases estrous cycle activity. Often the length of anestrus reflects the duration of hypercortisolism. Because cortisol can suppress all pituitary hormone synthesis and secretion, when HAC affects dogs during the first year of life, growth retardation may be obvious in addition to other more classic signs.

Answer 216

Although HAC is a slow, progressive disease, occasionally dogs may develop acute signs of severe lethargy, weakness, pale mucous membranes, and pain. This problem may occur as a consequence of acute intraabdominal or retroperitoneal hemorrhage.

Answer 217

High circulating cortisol concentration commonly results in lymphopenia in dogs with HAC, most likely from the result of steroid lympholysis. Eosinopenia is also common and it is caused by bone marrow sequestration of eosinophils. Excessive production of cortisol results in neutrophilia and monocytosis due to steroid-enhanced capillary demargination of these cells. These changes (i.e., neutrophilia without a left shift, lymphopenia, eosinopenia, and monocytosis) are called “stress leukogram,” a nonspecific finding that occurs in many sick dogs. Another frequent finding in the hemogram of dogs with HAC is mild erythrocytosis, related to direct stimulation of the bone marrow or to ventilatory problems. In addition, dogs with HAC commonly have increased platelet counts on CBC

Answer 218

The most consistent finding in dogs with HAC is a high serum alkaline phosphatase (ALP) activity. Alanine aminotransferase (ALT) activity is also commonly increased in dogs with HAC; however, those increases are usually mild to moderate. The increased ALT activity is believed to occur secondary to damage caused by swollen hepatocytes, glycogen accumulation, interference with hepatic blood flow, or hepatocellular necrosis.

Answer 219

Mild to moderate increases in the cholesterol and triglyceride concentrations are present in more than 50% of dogs. Glucocorticoid stimulation of lipolysis causes an increase in triglyceride and cholesterol concentrations. Mild fasting hyperglycemia is common in dogs with HAC, whereas overt diabetes mellitus (glucose >250 mg/dL) occurs in only about 5% to 10% of dogs with untreated HAC. Glucocorticoids increase hepatic gluconeogenesis and decrease peripheral utilization of glucose by antagonizing the effects of insulin. Dogs with HAC commonly have high basal and postglucagon insulin concentrations.

Answer 220

Glucocorticoids increase diuresis, causing a continual urinary loss of circulating urea nitrogen (blood urea nitrogen [BUN]). Approximately 30% to 50% of dogs with HAC have a low BUN. Hypophosphatemia has been reported to occur in approximately one third of dogs with HAC. This may result from a glucocorticoid-induced increase in urinary excretion of phosphate.

Answer 221

Complete urinalysis is an important component when evaluating any dog with PU/PD. Approximately 85% of dogs with Cushing's syndrome have a urine specific gravity s syndrome can, at least partially, concentrate the urine, it is recommended to have owners obtain a urine sample from their pet at home or at the time of initial examination

Answer 222

Glucosuria will occur in the approximately 5% to 10% of dogs with HAC and overt diabetes mellitus. Diabetes requires therapy regardless of whether the diagnosis of HAC has been confirmed

Answer 223

Many dogs with HAC have proteinuria, with a urine protein-to-creatinine ratio (UP : C) commonly ranging from 1 to 6 (normal, s syndrome, and they may represent a “cause-and-effect” relationship. Dogs with HAC are prone to UTI probably from chronic immunosuppression and a persistent bladder overdistention.

Answer 224

In dogs with alopecia, weight gain, lethargy, and hypercholesterolemia, both HAC and hypothyroidism should be included in the differential diagnosis. For this reason, dogs with HAC may be tested for hypothyroidism. Because HAC can affect thyroid function, it is common for a dog with HAC to be misdiagnosed as hypothyroid. To avoid this problem, HAC must be ruled out before testing for hypothyroidism, especially when a dog has clinical findings that are not typical of hypothyroidism (i.e., polyphagia, PU/PD, or a markedly elevated ALP).

Answer 225

Dogs with HAC are commonly in a hypercoagulable state that may be caused in part by an elevation of procoagulant factors (factors II, V, VII, IX, X, XII, and fibrinogen) and a decrease in antithrombin. Most dogs with PTE have hypovascular lung regions or alveolar pulmonary infiltrates. Hypovascular lung fields appear as areas of increased radiolucency and represent regions of reduced vascular filling distal to sites of thrombosis. Alveolar infiltrates correspond to areas of intrapulmonary atelectasis, hemorrhage, or infarction. Enlargement of the main pulmonary artery segment, right-sided cardiomegaly, and pleural effusion have been reported in dogs with PTE.

Answer 226

Because dogs with HAC have increased urinary calcium excretion

Answer 227

Because treatment options and prognosis can vary depending on the type of HAC. In dogs with a unilateral adrenal tumor, adrenalectomy may be the treatment of choice. If mitotane is the chosen treatment, the dose is usually higher for dogs with FAT than for those with PDH. Therefore, if the etiology is unknown, dogs that have a FAT may not respond to a dose of mitotane tailored for treatment of PDH. In addition, it is important to diagnose a FAT correctly so that owners can be informed of the risk of tumor growth (≈50% of FATs are carcinomas).

Answer 228

he urine cortisol–to-creatinine ratio (UCCR), the ACTH stimulation test, and the low-dose dexamethasone test (LDDST). None of these tests are 100% accurate and all of them have advantages and disadvantages. Therefore, veterinarians are best served if the accuracy, sensitivity, and specificity of each test is known. Endocrine testing should be delayed if a concomitant disease or a medication can affect results.

Answer 229

the LDDST, high-dose dexamethasone test, high-dose dexamethasone test using UCCR, measurement of the ACTH concentration, adrenal ultrasonography, CT, and MRI.

Answer 230

The measurement of the urinary corticoid excretion is a reflection of adrenal glucocorticoid secretion. By measuring urine cortisol in the morning urine sample, the concentration will reflect cortisol release over a period of several hours, thereby adjusting for fluctuations in plasma cortisol concentrations. The urinary corticoid (largely cortisol) concentration is related to the urinary creatinine concentration, thus providing the UCCR, in order to obtain a value independent of the degree of urine concentration. It should be considered that most corticoid measured in the urine is free cortisol.

Answer 231

Several studies on the diagnostic value of the UCCR have concluded that this test has a high sensitivity (close to 100%) but a low specificity (with values as low as 20%). Considering its high sensitivity, the UCCR has been advocated as a good test for ruling out HAC because a normal result makes the diagnosis unlikely (high negative predictive value) However, other diseases can also increase the UCCR in dogs and, for this reason, further investigation for HAC is warranted if the UCCR is elevated.

Answer 232

The ACTH stimulation test measures the response of the adrenal glands to maximal ACTH stimulation. It is considered a test of adrenal gland reserve and the best test to differentiate naturally occurring from iatrogenic HAC. In dogs with naturally occurring HAC, an exaggerated response to ACTH administration is expected, whereas dogs with iatrogenic HAC typically have a low-normal or a diminished response.

Answer 233

The sensitivity of an ACTH stimulation test for diagnosing naturally occurring HAC is 60% to 85% and the specificity is 85% to 90%. The sensitivity is higher (up to 85%) for the diagnosis of PDH than for the diagnosis of FAT (≈60%).

Answer 234

It cannot differentiate PDH from an FAT. However, it is the only test that can differentiate iatrogenic from naturally occurring HAC. Also, because this test is frequently used to monitor medical therapy, some have suggested that it is helpful to know the stimulation capacity of the adrenal glands prior to treatment.

Answer 235

Normally, glucocorticoids (e.g., dexamethasone) have negative feedback effects on the pituitary gland, suppressing ACTH secretion. As circulating ACTH decreases, cortisol secretion from the adrenal cortex also diminishes. This test takes advantage of the fact that, in dogs with HAC, the pituitary-adrenal axis controlling ACTH and cortisol secretion is abnormally resistant to dexamethasone suppression.

Answer 236

Not only because it is a potent glucocorticoid, but also because it does not cross-react with the standard cortisol assays, allowing the use of serum (plasma) or urine measurements as an endpoint.

Answer 237

Compared with the ACTH stimulation test, the LDDST is much more sensitive in confirming HAC because the results are diagnostic in virtually all dogs with cortisol-secreting adrenal tumors and in 90% to 95% of dogs with PDH.

Answer 238

In contrast to the ACTH stimulation test, the LDDST is not helpful in the detection of iatrogenic HAC. The test is also affected by more variables than the ACTH stimulation test, takes 8 hours to complete (or 3 days, if urine samples are collected; see later), and does not provide pretreatment information that may be used in monitoring the effects of mitotane or trilostane therapy.

Answer 239

It is consistent with a diagnosis of HAC. Although basal and 8-hour postdexamethasone samples are most important for test interpretation, one or more samples taken at intermediate times (e.g., 4 hours) during the test period may also be helpful.

Answer 240

They most likely have PDH. Approximately 65% of dogs with naturally occurring PDH demonstrate any of these types of suppression. Interpretation of the results of the LDDST should be based on the laboratory's reference ranges. Failure to show suppression (serum or plasma cortisol at both 4 and 8 hours >1.4 µg/dL and >50% of basal cortisol concentration) is diagnostic for HAC but cannot aid in determining the cause.

Answer 241

The sensitivity of the LDDST is excellent, approximately 90% to 95% in dogs with PDH and virtually 100% in dogs with FAT. The specificity of the LDDST, however, can be low (40% to 50%), especially when measured in a population of sick dogs. Because of the low specificity of this test, diagnosis of HAC should never be based on results of an LDDST alone, especially in a dog with nonadrenal disease. It is best to delay testing for HAC until the dog has recovered from the concurrent illness.

Answer 242

This test can identify PDH if one of the suppression criteria is met (a 4-hour cortisol concentration 1 µg/dL). Following these criteria, approximately 65% of dogs with naturally occurring HAC can be identified as PDH with the LDDST. Dexamethasone resistance (none of the previously mentioned criteria are met) occurs in about 40% of dogs with PDH and in virtually all dogs with an FAT. In such dogs another differentiating test must be used.

Answer 243

The ability of glucocorticoids, such as dexamethasone, to suppress pituitary ACTH secretion in dogs with PDH is abnormal. Most PDH dogs have some resistance to suppression with low doses of dexamethasone, but much higher doses of dexamethasone can overcome this resistance to negative-feedback inhibition.

Answer 244

In contrast, because pituitary ACTH secretion has already been chronically suppressed in dogs with cortisol-secreting adrenal tumors, administration of dexamethasone will fail to suppress serum cortisol concentrations, even at high doses.

Answer 245

Unfortunately, lack of cortisol suppression is not always diagnostic for an adrenal tumor because 15% to 50% of dogs with PDH fail to demonstrate cortisol suppression. In general, the larger the pituitary tumor, the less likely the dog is to suppress with dexamethasone, even with high doses.

Answer 246

Advantages of this test are that it can be performed at home and it is sensitive. Disadvantages include the limited specificity of the UCCR and possible owner error associated with administration of the dexamethasone tablets.

Answer 247

Measurement of basal endogenous ACTH concentrations is of no value in the diagnosis of HAC because dogs with the disease commonly have values within reference range limits. On the other hand, measurement of plasma ACTH concentrations is an extremely reliable means of determining the cause of HAC once the diagnosis has been confirmed. There is relatively little overlap in ACTH concentrations between dogs with pituitary tumors and those with adrenal tumors, making this a valuable discriminatory test. Endogenous ACTH concentrations are normal to high in dogs with PDH, whereas ACTH concentrations are usually low or undetectable in dogs with FAT or with iatrogenic HAC Unfortunately, about 20% of dogs with HAC have random plasma ACTH concentrations in the non diagnostic range. Adrenal ultrasonography is an extremely valuable tool for differentiating PDH from an FAT

Answer 248

Most dogs with PDH are treated medically in an attempt to decrease ACTH secretion (i.e., Selegiline), to inhibit the synthesis of adrenal cortex hormones (i.e., trilostane or ketoconazole), or to cause partial or complete necrosis of the adrenal cortex (i.e., mitotane). Mitotane and trilostane are both effective (Ketoconazole and selegiline are less effective). Dogs seem to tolerate trilostane better than mitotane; however, both treatments have potential serious side effects. Medical treatment aimed at the adrenal cortex (trilostane or mitotane) to lower plasma cortisol concentrations may increase ACTH secretion. This may enhance growth of the pituitary tumor, although most research suggests that tumor growth is independent of circulating cortisol concentrations

Answer 249

Trilostane is a synthetic steroid analogue that acts mainly as a competitive inhibitor of the 3 beta hydroxysteroid dehydrogenase (3 beta-HSD) enzyme. This enzyme system mediates the conversion of pregnenolone to progesterone in the adrenal cortex. This inhibition of progesterone synthesis also blocks the synthesis of its end products, particularly circulating cortisol and, to a lesser extent, aldosterone. The decrease in plasma cortisol concentration and the increase in 17-alpha-OH-pregnenolone and dehydroepiandrostenedione concentrations confirm an inhibitory effect of trilostane on the 3-beta-HSD. If a dog being treated with trilostane has clinical signs consistent with hypocortisolism, one should stop therapy and perform an ACTH stimulation test to confirm whether clinical signs are due to hypocortisolism. If hypoadrenocorticism persists, adrenal necrosis is likely.

Answer 250

Mitotane is an adrenocorticolytic agent with a direct cytotoxic effect on the adrenal cortex, resulting in selective, progressive adrenocortical necrosis and atrophy. Mitotane causes selective necrosis of the zona fasciculata and zona reticularis of the adrenal cortex (sites of glucocorticoid production). The zona glomerulosa (site of mineralocorticoid production) is less sensitive to this drug; however, at high doses, mitotane can cause complete necrosis of the adrenal cortex. Mitotane is fat soluble and should always be administered with a meal. This drug can be used in an attempt to cause partial destruction of the adrenal cortex, preserving the zona glomerulosa (standard protocol) or complete necrosis of the entire adrenal cortex (nonselective protocol). If the veterinarian elects not to provide glucocorticoid supplementation during the induction periodIt it is imperative that owners be supplied with prednisone or prednisolone in case signs of life-threatening hypoadrenocorticism develop and immediate veterinary care is not available. Once adrenal reserve has been appropriately reduced, as determined by ACTH stimulation test results, mitotane should be continued at a maintenance dosage

Answer 251

Ketoconazole is an imidazole antifungal drug that also inhibits the synthesis of glucocorticoids and androgens. It effectively lowers circulating cortisol concentrations but has minimal effect on mineralocorticoid production.

Answer 252

In dogs, the neurotransmitter dopamine appears to primarily inhibit the secretion of ACTH peptides from the pars intermedia and a central disturbance of dopamine may play a role in the pathogenesis of canine Cushing's disease. L-deprenyl (selegiline HCL) is a selective and irreversible inhibitor of monoamine oxidase type B, which helps restore the central dopamine concentration and facilitates dopaminergic transmission by several mechanisms. L-deprenyl may down-regulate ACTH secretion by enhancing the dopamine concentration.

Answer 253

Including calcium oxalate urolithiasis, calcinosis cutis, and mineralization of other soft tissue (respiratory tract and kidney). Glucocorticoids may increase urinary calcium excretion, which in turn may increase the risk of development of calcium-containing uroliths. One study found that dogs with Cushing's syndrome had a tenfold higher risk of developing calcium-containing uroliths than dogs without Cushing's syndrome.

Answer 254

Hypercortisolism in Cats (Feline Cushing's Syndrome:

Answer 255

As in the dog, naturally occurring HC in the cat can be caused by either an adrenocorticotropic hormone (ACTH)–secreting tumor of the pituitary gland or a cortisol-secreting tumor of the adrenal cortex. Despite the severe pathophysiologic consequences of hypercortisolemia caused by excessive ACTH, these pituitary tumors are usually benign. Most are adenomas. Nearly two thirds of adrenal tumors associated with FCS are benign adenomas, and the remainder are malignant adenocarcinomas. Pituitary-dependent disease accounts for approximately 80% of cases of FCS.

Answer 256

Cats are considered less prone to the deleterious effects of glucocorticoids than dogs and this might account for their lower incidence of naturally occurring HC. One study demonstrated that cat skin and liver have decreased density of glucocorticoid receptors and lower binding affinity.[6] This may explain cats’ decreased sensitivity to the effects of glucocorticoids. This perceived difference in steroid sensitivity may merely reflect the possibility that clinical signs could be more difficult to detect in cats.

Answer 257

Even if they are less prone to developing adverse side effects associated with exogenous glucocorticoids, iatrogenic Cushing's syndrome exists in cats. Clinical case reports have described iatrogenic Cushing's syndrome in cats with abdominal enlargement, dermatologic abnormalities, and biochemical abnormalities similar to those seen in naturally occurring HC. Dermatologic abnormalities have most commonly included hair loss, skin atrophy, and skin fragility, but hyperpigmentation, medially curled pinnae, and bruising have also been reported. In one study, high doses of glucocorticoids were associated with neutrophilia, lymphopenia, and eosinopenia, and with increased serum concentrations of cholesterol, triglycerides, and glucose, but overt clinical signs of HC were uncommon. One of 14 cats developed medial curling of the pinnae. This uncommon clinical sign is thought to be due to catabolic effects of glucocorticoids on cartilage and has been reported in cats with iatrogenic Cushing's syndrome, but not in cats with the naturally occurring disease. Polyuria and polydipsia were also reported, but this was not supported by urinalysis results in which urine specific gravity remained above 1.035 in all cats.

Answer 258

Glucosuria causes an osmotic diuresis, resulting in primary polyuria followed by compensatory polydipsia. It is not known if endogenous glucocorticoid excess of feline HC is a direct cause of PU/PD, as is suspected in dogs. Table • 293-1 -- Approximate Frequency of Clinical Findings in Cats with Hyperadrenocorticism Diabetes mellitus is extremely common in FCS, more so than in other species. The reason for this is unclear, but it might reflect the possibility that only the most severe cases of FCS are being diagnosed.

Answer 259

.....the inability of cells to use glucose as a source of energy.

Answer 260

.....glucocorticoid-induced suppression of dermal fibroblast and keratinocyte proliferation, as well as down-regulation of collagen, hyaluronic acid, sulfated glycosaminoglycans, elastin, and tenascin-C expression. Cats with HC often develop severe skin fragility such that the skin is easily torn

Answer 261

......including decreased macrophage expression of inflammatory cytokines, increased expression of some antiinflammatory cytokines, decreased function and maturation of dendritic cells, decreased T cell activation and proliferation in response to mitogens, decreased NK cell–mediated lysis of target cells, decreased mitogen-induced B cell proliferation, and decreased antibody production

Answer 262

.......glucocorticoid-stimulated depletion of glucogenic amino acids from skeletal muscle required to meet increased demand for hepatic gluconeogenesis substrate availability

Answer 263

....glucocorticoid-induced enlargement of the liver, with histologic changes of hepatocellular swelling and glycogen-containing cytoplasmic vacuolization in the dog. Maybe in cats as well?

Answer 264

First, it has been proposed that cats lack a glucocorticoid-induced ALP isoenzyme.[22] Second, the half-life of ALP in the cat is extremely short, making it more difficult to detect an increase. Neither of these explanations exclude the presence of steroid hepatopathy, so it may be that it is simply more difficult to detect. Increased liver enzyme activity has been observed in both naturally occurring and iatrogenic Cushing's syndrome in cats.

Answer 265

Unlike dogs with HC, cats with the disease, while commonly reported as exhibiting PU/PD, often maintain their ability to concentrate their urine. In a study of long-term, high-dose exogenous glucocorticoids, urine specific gravity remained above 1.035 in all cats, with or without glycosuria. If a cat with HC exhibited isosthenuria, one should be concerned about concurrent chronic renal disease. It should be noted that the presence of glucose in the urine does not significantly increase urine specific gravity, which might falsely overestimate urine concentrating ability. . When measured by refractometry, urine specific gravity increases only 0.002 for every 10 g/L of glucose

Answer 266

Glucocorticoids on renal tubules, but it could also be related to underlying glomerular disease.

Answer 267

Is inconsistency. The expected findings of lymphopenia, eosinopenia, monocytosis, and neutrophilia have been demonstrated in cats treated with exogenous glucocorticoids, but not in cats with naturally occurring disease. The classic “stress leukogram” can occur, but cats with HC have been observed with wide ranges of white cell counts and differentials. Leukopenia has not been reported in FCS. Platelet and red blood cell counts are usually normal.

Answer 268

Hypercholesterolemia has been reported commonly in cats with HC. Glucocorticoids inhibit lipoprotein lipase activity and increase the activity of hormone-sensitive lipase. The combined result is an increase in triglycerides and cholesterol. Serum triglyceride concentrations have not been reported in cats with HC but have been reported as elevated in cats with iatrogenic

Answer 269

Liver enzyme activities can be abnormal in cats with HC. Increased activity of alanine aminotransferase (ALT) is seen commonly, but it is not known if this reflects abnormal liver function or significant hepatocellular damage.

Answer 270

Liver disorders unrelated to glucocorticoid excess have been observed in some cats with HC. Diabetic cats can have hepatic lipidosis, providing another possible explanation for increased liver enzyme activity in cats with HC. Concurrent HC and hyperthyroidism have also been reported, and hyperthyroidism is commonly associated with increased ALT activity.

Answer 271

When ALP elevations are seen in a cat with HC, it could be due to an unrelated or a secondary cholestatic condition (e.g., hepatic lipidosis). Also, hepatocellular swelling associated with steroid hepatopathy, if severe enough, could account for a degree of cholestasis. Because of the short half-life of ALP in the cat, an elevation in ALP activity should be taken seriously because it reflects significant active cholestasis.

Answer 272

No, the ACTH stimulation test is not sensitive in detecting cats with HC. Because of the poor sensitivity and unknown specificity, the ACTH stimulation test is not recommended for diagnosis of FCS.

Answer 273

First, although cats excrete less cortisol in their urine than do dogs, normal UCCRs are reportedly higher, so care must be taken to use reference intervals specific to the cat. Second, although ample evidence suggests that the UCCR is highly sensitive in the cat,[30] data concerning specificity of the UCCR in the diagnosis of feline HC are lacking. There are reports of increased UCCRs in sick cats with non adrenal illness and, in particular, in cats with hyperthyroidism. It is likely that the UCCR is not specific for FCS.

Answer 274

In the dog, this test has a high negative predictive value, making it valuable as a simple and inexpensive screening test for HC. Similarly, if a cat has a negative UCCR, a diagnosis of HC should be considered highly unlikely. A high UCCR in a cat suspected of having HC is supportive of the diagnosis but does not confirm it. Based on these principles, it is recommended to use the UCCR as a screening test for HC in cats.

Answer 275

Dexamethasone dosages of 0.01 or 0.015 mg/kg of dexamethasone, typically used for the LDDST in dogs, do not consistently suppress serum cortisol concentrations in the cat. Using these doses, the LDDST has 100% sensitivity for feline HC, but, as with the UCCR, the specificity is unknown and could be quite low. Higher doses of dexamethasone are necessary to reliably suppress serum cortisol concentrations in normal cats. To perform the LDDST in a cat, 0.1 mg/kg dexamethasone is administered intravenously and the serum samples are collected for cortisol measurement at 4 and 8 hours postdexamethasone. The sensitivity of this test, using the 0- and 8-hour postdexamethasone serum cortisol concentrations, approaches 100%, but again, the specificity is unclear. Because adrenal tumors secrete cortisol uncontrolled by pituitary ACTH, it seems reasonable that an LDDST result showing suppression of cortisol at 4 hours postdexamethasone, with escape from suppression at 8 hours, would be interpreted as consistent with pituitary-dependent HC. (The LDDST can also be combined with the UCCR in a way that allows the diagnostic test to be performed by cat owners at home.)

Answer 276

To perform the HDDST, 1 mg/kg of dexamethasone should be given IV and samples collected for measurement of serum cortisol concentrations at time zero, and 4 and 8 hours later. Roughly 50% to 65% of cats with pituitary-dependent HC will exhibit suppression of serum cortisol at either or both postdexamethasone time points. If a diagnosis of HC is established, therefore, this test can be specific for pituitary-dependent disease. The limitation of the HDDST is that it cannot reliably differentiate between an adrenal tumor and pituitary-dependent HC when the postdexamethasone cortisol concentrations are not suppressed. Lack of suppression can occur in 50% of cats with pituitary-dependent HC, meaning the HDDST has the diagnostic accuracy of a coin toss in these patients. Cats with adrenal tumors, in general, do not exhibit suppression of serum cortisol during the HDDST. Therefore, serum cortisol suppression on HDDST is useful but lack of suppression is not. (Some authors recommend the use of absolute cortisol concentration values in combination with determination of percent suppression from the baseline cortisol concentration in interpreting the HDDST. A postdexamethasone serum cortisol concentration of 50% from baseline are considered positive test results)

Answer 277

Measurement of endogenous ACTH is probably a superior test for differentiating between adrenal tumors and pituitary-dependent HC. If HC is caused by oversecretion of ACTH from a pituitary adenoma, circulating ACTH concentrations should be high or, because secretion of ACTH is episodic, normal. No cats in the literature have been incorrectly identified as having adrenal tumors based on low endogenous ACTH concentrations.

Answer 278

By most reports, mitotane is ineffective in cats. Given the lack of other highly useful and well-studied drugs, trilostane is a reasonable choice for treatment of feline HC. There are no reports of ketoconazole used in cats with HC, but one study of the long-term effects of high-dose ketoconazole in cats showed no suppression of basal serum cortisol concentrations after 30 days. Still, the drug is well tolerated in cats and it is reasonable to consider its use in the medical management of HC in cats. Given the lack of effective medical options for treatment of HC in cats, adrenalectomy is often considered the best treatment option.

Answer 279

Low-dose dexamethasone suppression (LDDS) and the corticotropin stimulation test work on the principle of suppression or stimulation of the pituitary-adrenal axis.

Answer 280

LDDS: dexamethasone is adm at a low dosage to cause negative feedback to the pituitary gland; normally decreasing the endogenous corticotropin secretion and resultant decrease in circ cortisol conc. Dexamethsone is the only synthetic corticoisteroid that does not cross-react with the cortisol assay. Corticotropin stimulation is use to determine the extent of adrenal enlargement. Adrenal gland that are enlarged because of chronic pituitary stimulation by corticotropin or that are neoplastic show an exaggerated response to exogenous corticotropin.

Answer 281

Electrolyte balance and blood pressure homeostasis represent the principal physiologic effects of mineralocorticoids. These actions are carried out at the level of the distal tubules in the kidney.

Answer 282

The effect of the mineralocorticoids is to promote retention of sodium and secretion of potassium (passive mechanism: potassium is retained in the renal filtrate to maintain the osmolality of urine) and hydrogen.

Answer 283

The cellular response to mineralocorticoids is to synthesize a protein that increases the permeability of the luminal cell surface to sodium influx from the renal filtrate and increases Na+, K+-ATPase activity in the contraluminal cell surface, which allows movement of sodium out of the cell into the interstitial tissue.

Answer 284

In situations of excessive mineralocorticoid production: sodium retention leads to increased extracellular fluid volume, thereby causing hypertension. Conversely, low blood pressure occurs as a result of inadequate secretion of mineralocorticoids.

Answer 285

Hypersecretion of mineralocorticoids can also lead to excessive hydrogen ion loss, and metabolic alkalosis, whereas hyposecretion can result in increased retention of hydrogen ion and metabolic acidosis.

Answer 286

By the renin-angiotensin axis, the plasma concentration of potassium , and to a minor extent, the plasma sodium and ACTH conc.

Answer 287

Cells in the juxtaglomerular apparatus of the kidney produce the enzyme renin in response to decreases in blood pressure (decreased extracellular fluid volume), which causes a reflex increase in renal nerve discharge and increased renal intraarterial mean pressure. This results in increased renin secretion from the juxtaglomerular cells that surround the afferent arterioles as they enter the glomeruli.

Answer 288

Renin acts on angiotensinogen, an alpha 2 globulin produced by the liver and present in the circulation, and this results in the production of angiotensin I, a decapeptide. Angitensin I is further hydrolyzed to angiotensin II, an octapeptide by ACE.

Answer 289

Angiotensin II stimulates the zona glomerulosa to produce mineralocorticoids. Angiotensin II also increases peripheral resistance of the blood vascular system by causing vasoconstriction of smooth muscle of the blood vessels. Angiotensin II, if present on a long-term basis, also increases the size of the zona glomerulosa.

Answer 290

. Increased plasma potassium concentration and angiotensin II both markedly increase aldosterone release from the adrenal cortex:

Answer 291

Ang II causes increased aldosterone synthesis and secretion by secreting conversion of cholesterol to pregnenolone and corticosterone to aldosterone. The other major regulatory factor in the control of mineralocorticoid (such as aldosterone) secretion is the blood potassium concentration: Increase in potassium conc; stimulates the zona glomerulosa to secrete mineralocorticoid, and vice versa. This stimulation is independent of the RAS.

Answer 292

Evidence exist that cells of the macula densa (located at the distal tubule of the kidney) exert control on the RAS through sensing of changes in sodium concentration (but also chloride ions conc) in tissue fluids. Sodium increase results in decreased renin release, and vice versa; thereby restoring the mineralocorticoid concentration to normal.

Answer 293

Total absence of ACTH can decrease aldosterone secretion, but ACTH has little effect in controlling the rate of secretion and hypophysectomy does not result in mineralocorticoid deficiency.

Answer 294

Mineralocorticoids has a sodium conserving effect, in contrast to ANP (amino-acid peptide); which reduces sodium retention by the kidneys. ANP also causes peripheral vasodilatation; thereby lowering blood pressure. ANP may also inhibit the production of mineralocorticoids and renine.

Answer 295

Mineralocorticoids increase absorption of sodium and secretion of potassium in the kidney, sweat glands, salivary glands, and intestinal epithelial cells. Thus, aldosterone in critical in conserving body salt. The main site of action in the kidney is the principal cells of collecting tubules and, to a lesser extent, the distal tubules and collecting duct.

Answer 296

Aldosterone also causes secretion of hydrogen ions in exchange fo sodium in the intercalated cells of the cortical collecting tubules. Thus a deficiency of aldosterone can cause mild metabolic acidosis.

Answer 297

Results from failure of the adrenal glands to secrete adequate quantities of corticosteroids to support normal clinical function. More than 85% of adrenal gland reserve must be lost before clinical signs of hypoadrenocorticism are manifested. Thus, bilateral adrenal gland dysfunction is always present in animals with clinical signs of adrenal failure.

Answer 298

The most common cause of hypoadrenocorticism is primary adrenal failure. It is believed that immune-mediated adrenalitis is the most likely etiology in most dogs with naturally occurring primary hypoadrenocorticism. Other more unusual causes of primary hypoadrenocorticism include granulomatous destruction, hemorrhagic infarction of the adrenal gland, amyloidosis, necrosis, and metastatic neoplasia. Although the adrenal glands are a common site for metastasis in a number of tumor types, only lymphoma has been reported to cause adrenal gland failure in dogs and cats. Primary adrenal failure may also be caused by drugs such as mitotane and trilostane. Adrenal suppression caused by trilostane is usually reversible, but permanent primary hypoadrenocorticism due to adrenal necrosis and hemorrhage has been reported. Adrenal necrosis has been speculated to be caused by high circulating ACTH concentrations.

Answer 299

Hypothyroidism, diabetes mellitus, and hypoparathyroidism.

Answer 300

both glucocorticoids (primary cortisol) and mineralocorticoids (primarily aldosterone). In some cases of primary adrenal gland failure, mineralocorticoid secretion is not impaired and clinical signs are due to deficiency of glucocorticoids alone.

Answer 301

A rare cause of hypoadrenocorticism is pituitary dysfunction, resulting in decreased or absent adrenocorticotropic hormone (ACTH) secretion and secondary adrenal failure.

Answer 302

Neoplasia, inflammation, or trauma.

Answer 303

Hypophysectomy for the treatment of pituitary-dependent hyperadrenocorticism usually results in permanent secondary hypoadrenocorticism. Withdrawel of exogenous glucocorticoid drugs is the most common cause of secondary hypoadrenocorticism.

Answer 304

Administration of exogenous glucocorticoids (topical, oral, or injectable) causes rapid suppression of ACTH production from the pituitary gland, with resultant secondary adrenal atrophy. Duration of adrenal axis suppression depends on the potency and half-life of the administered glucocorticoid. Long-acting depot drugs are the most potent adrenal suppressant s and can cause suppression for 5-6 weeks or longer. ACTH deficiency results in primarily glucocorticoid deficiency because ACTH deficiency has only a minor influence on mineralocorticoid secretion by the adrenal gland.

Answer 305

Clinical signs are typically vague and none are pathognomonic for the disease. Anorexia, vomiting, lethargy, depression, weakness, weight loss, diarrhea, and shaking or shivering are all common; polyuria, polydipsia, and abdominal pain may also be observed. All of these clinical signs may be caused by glucocorticoid deficiency alone; however, when mineralocorticoid deficiency is also present, polyuria, polydipsia, hypovolemic chock, collapse, and dehydration are more common manifestations of Addison’s disease include seizures due to hypoglycemia, episodic muscle cramping, and gastrointestinal hemorrhage. Causes of gastrointestinal hemorrhage include ischemia due to severe hypovolemia, and the effect of cortisol deficiency on the mucosa of the gastrointestinal tract.

Answer 306

Poor body condition, lethargy, weakness, severe dehydration, abdominal pain, bradycardia, weak pulses, hypothermia, decreased capillary refill time, and other signs of hypovolemic shock may be evident on physical examination. There may also be evidence of melena or hematochezia. In some dogs with hypoadrenocorticism, especially those with glucocorticoid deficiency alone, the physical examination may be unremarkable. Physical examination of animals in an acute hypoadrenal crisis reveals weak pulse, bradycardia, prolonged capillary refill time, severe mental slowness, and profound muscle weakness. Suspicion of the disease should be raised in a dog with a normal or slow heart rate in the presence of circulatory shock, and the “waxing and waning” course of disease before collapse.

Answer 307

Electrolyte abnormalities consisting of hyperkalemia, hyponatremia, hypochloremia, nonregenerative anemia, and lymphocytocic; however, these changes are not present in all cases. Some dogs have no classic clinicopahtologic abnormalities. Azotemia and hyperphosphatemia also accompany primary hypoadrenocorticism, which makes it difficult to differentiate it from acute renal failure.

Answer 308

Dehydration and hypovolemia, or increase in BUN may be caused by gastrointestinal hemorrhage.

Answer 309

Hypercalcemia is seen in approx. 30% of the dogs. Hypocalcemia has also been shown present in some affected dogs (9%), but this may have been the result of concurrent hypoalbuminemia.

Answer 310

Hyponatremia and hyperkalemia is caused by aldosterone deficiency with a resultant failure of the kidneys to conserve sodium. Because sodium ions are exchanged for either potassium or hydrogen ions, impairment of renal tubular potassium and hydrogen secretion causes hyperkalemia and mild metabolic acidosis. Failure to conserve sodium results in profound fluid loss, shift of K+ ions to the extracellular compartment, prerenal azotemia due to decreased renal perfusion, and progressive hypovolemia. The mechanism by which hypercalcemia (total increased, ionized may be increased or decreased) occurs is unknown. Acidemia can lead to mild ionized hypercalcemia by decreasing protein binding.

Answer 311

Acidemia can lead to mild ionized hypercalcemia by decreasing protein binding.

Answer 312

Reasons for normal electrolytes in dogs with hypoadrenocorticism include secondary hypoadrenocorticism due to decreased ACTH secretion, concurrent illness such as hypothyroidism that can mask electrolyte changes, selective desctruction of the ZF and ZR, or early-stage disease in which destruction of the ZG is not complete. Concurrent diseases causing anorexia and concurrent hypothyroidism can also blunt the typical electrolyte changes of hypoadrenocorticism.

Answer 313

Energy metabolism is diminished, owing to impaired gluconeogenesis, impaired fat metabolism, decreased fat utilization, and depletion of liver glycogen stores. As a result, fasting hypoglycemia may occur. Associated with these processes could be mental changes, such as lethargy.

Answer 314

Eosinophilia, neutrophilia, and lymphocytosis (or eosinophil and lymphocyte counts may be normal in the presence of severe metabolic stress), and nonregenerative normocytic normochromic anemia. However, these changes are seen in only 10% to 30% of dogs. In some dogs, the mild anemia is masked by dehydration.

Answer 315

The absence of a stress leukogram (an abnormal finding in the presence of systemic illness).

Answer 316

The anemia of hypoadrenocorticism has classically been attributed to lack of glucocorticoid effects on the bone marrow. However, more recent studies have suggested that hemorrhagic gastroenteritis contributes significantly to the anemia. Although hypoglycemia is more common with secondary or atypical hypoadrenocorticism, it is rarely seen with typical hypoadrenocorticism.

Answer 317

Urine specific gravity is frequently low, and this finding is attributed to medullary washout (inadequate medullary gradient caused by sodium depletion) and decreased medullary blood flow. Dilute urine in the presence of azotemia and hyperkalemia may easily be mistaken for acute renal failure. Hormonal assays are necessary to confirm the presence or absence of adrenal disease and to differentiate between hypoadrenocorticism and renal failure.

Answer 318

Clinical signs, classic electrolyte imbalances, and confirmation with a corticotropin response test. The baseline cortisol sample should be collected with the initial blood work and synthetic corticotropin should be administered intravenously during the initial fluid therapy. A 1-hour , post-corticotropin sample may then be drawn and glucocorticoids may be adm after the 1-hour sample is taken. Intramuscular injection of corticotropin (gel or synthetic) may not be absorbed in animals in circulatory chock; therefore, intravenous adm of synthetic corticotropin is preferred.

Answer 319

Dogs and cats with primary hypoadrenocorticism exhibit a subnormal response to corticotropin adm. Both baseline and post-corticptropin cortisol concentrations are usually low or undetectable.

Answer 320

Endogenous plasma corticotropin concentrations are dramatically increased in animals with primary hypoadrenocorticism as a result of loss of negative feedback to the pituitary gland, which is caused by decreased serum cortisol concentrations. In the case of secondary hypoadrenocorticism, which is caused by a pituitary deficiency of corticotropin, the endogenous corticotropin concentrations are typically decreased (

Answer 321

Cells of the adrenal medulla are the equivalent of postganglionic cells of the sympathetic nervous system. Both epinephrine and norepinephrine are released when preganglionic nerve fibers to the adrenal medulla are stimulated.

Answer 322

Norepinephrine is the neurotransmitter of the sympathetic nervous system. Most of the norepinephrine found in plasma originates from the adrenal medulla.

Answer 323

The synthesis of catecholamines is from the amino acid tyrosine (also phenylalaline). The main catecholamine synthesized by the chromaffin cells in the adrenal medulla is epinephrine. The cells that produce epinephrine are different from those that synthesize norepinephrine.

Answer 324

Acetylcholine release from the preganglonic nerve fibers initiates the synthesis of the catecholamines by the medullary cells, and acetylcholine also stimulates the release of catecholamines from chromaggin granules; a phenomenon called stimulus-secretion coupling.

Answer 325

Tyrosine hydroxylase is the rate limiting enzyme in the formation of catecholamines. The end products of tyrosine metabolism, including DOPA, dopamine, norepinephrine, and epinephrine, inhibit the activity of tyrosine hydroxylase. Fig 33-16. S 357 Cunningham. Tyrosine---DOPA (dihydroxyphenylaline): (occurs in the cytosol)---Dopamine---Norephinephrine (occurs within the chromaffin granule)---Epinephrine –Catechol + Amine

Answer 326

The metabolism of catecholamines is rapid (2 min for norephinephrine, less for epinephrine) and is accomplished mainly in the liver and kidneys.

Answer 327

Cortisol (from the adrenal cortex) is important for the activity of the enzyme phenyleethanolamine-N-methyltransferase.

Answer 328

The primary actions of catecholamines are on the metabolism, especially effects that increase the concentration of glucose.

Answer 329

The actions of catecholamines are mediated through adrenergic receptors located on target tissues. There are 2 major types of receptors; α and β, which are subdiveided into α1 and α2 and β1 and β2. The α receptors control catecholamine release from sympathetic nerve endings, α1 affecting postsynaptic nerve endings and α2 affecting presynaptic terminals. β1 receptors affect mainly the heart, and β2 receptors affecting smooth muscle contraction and intermediary metabolism.

Answer 330

Whereas all adreneregic receptors are responsive to both epinephrine and norepinephrine, the responses to the 2 catecholamines are different. The metabolic effects of catecholamines are mediated mainly by β2 receptors, mainly by epinephrine.

Answer 331

The effects of epinephrine on glucose metabolism are similar to those of glucagon and opposite to those of insulin. Epinephrine increases blood glucose conc, with the effect mainly I the liver; that is epinephrine promotres both hepatic glycogenolysis and gluconeogenesis.

Answer 332

Epinephrine also stimulates glycogenolysis in skeleltal muscle, which in this situation is in contrast with action of glucagon : In the muscles lactate is produced instead of glucose; the liver takes up lactate and converts it to glucose. Additional effects on glucose metabolism include the inhibition of insulin secretion (through α receptors) and stimulation of glucagon secretion by the pancreas; both actions increase blood glucose concentrations.

Answer 333

Epinephrine promotes lipolysis through interaction with 2 receptors on adipose cells. Activation of a lipase enzyme results in an increase in free fatty acids in the blood. Glucocorticoids potentiate the effect of epinephrine on lipolysis.

Answer 334

Catecholamine stimulate cardiac function. Both epinephrine and norepinephrine interact with β1 receptors to increase both the force of contraction and the heart rate; the latter resulting from the promotion of a shorter period of diastolic depolarization. Whereas both catecholamines promote arteriolar constriction through its high affinity for α receptors, epinephrine, through its high affinity for β2 receptors, causes the dilation of blood vessels both in the heart and in the skeletal muscle. The end result is that total peripheral resistance is decreased by the action of epinephrine with a concomitant decline in diastolic pressure; however, blood pressure is changed little, and cardiac output increases because of the increase in heart rate. The action of epinephrine to increase cardiac output is an obvious beneficial effect in situations that are described as “flight or fight”.

Answer 335

Catecholamines affect smooth muscle. Epinephrine causes relaxation of bronchial smooth muscle, particularly in situations in which the muscle is in a contracted state. As the action is mediated through β2 receptors, norepinephrine has little effect on bronchial smooth muscle. Epinephrine causes relaxation of the smooth muscle of the GI tract through interaction with β2 receptors.

Answer 336

Catecholamine stimulation of α receptors results in contraction of uterine smooth muscle, and stimulation of β2 receptors results in relaxation. Because of its dominant effect on β2 receptors, epinephrine causes relaxation of the uterus, whereas both epinephrine and norepinephrine interact with α receptors to cause contraction.

Answer 337

The effets of the catecholamines on the bladder smooth muscle are dependent on different locations of α and β receptors; α receptors located within the neck of the bladder, and β receptors are located within the body of the bladder; Epinephrine relaxes the body and contracts the neck of the bladder, norepinephrine contracts the neck of the bladder= net effect is retention of urine.

Answer 338

In the eye, epinephrine causes relaxation of the lens through stimulation of β receptors on the ciliar muscles. It causes dilation of the pupil through stimulation of α receptors; with resultant contraction of the radial muscle of the iris.

Answer 339

The effects of epinephrine on the central nervous system are excitatory. Drugs that affect the CNS probably do so by modulation of catecholamine concentrations, whereby sedation is associated with lower values of epinephrine. Other effects of catecholamine include the promotion of sweating and piloerection. Epinephrine also increases renin production by the renal juxtaglomerular cells. Summary effects: Table 33-5 s 359.

Answer 340

The main factors that stimulate catecholamine secretion are hypoglycemia (within normal physiologic limits) and conditions that produce stress. In contrast, other parts of the sympathetic nervous system are depressed by decrease in blood glucose levels.

Answer 341

Catecholamines are especially important for the maintenance of blood pressure in conjunction with severe blood loss; decreased blood pressure stimulates epinephrine secretion. Decreased temperature increases epinephrine secretion.

Answer 342

Stress: The response to stress can be particularly marked because each preganglionic sympathetic neuron that supplies the adrenal medulla affects a number of chromaffin cells; that is, the signal is greatly amplified.

Answer 343

Hormones of the pancreas The pancreas has important endocrine and nonendocrine functions. The nonendocrine functions occur as a result of activity of the exocrine part of the pancreas and are concerned with GI function.

Answer 344

The endocrine portion of the pancreas is organized as discrete islets (islets of Langerhans) that contain 4 cell types, each of which produces a different hormone. The most numerous of the islet cells are β cells, which produce insulin; α cells produce glucagon, D cells produce somatostatin, and F or PP cells produce pancreatic polypeptide. Although these hormones have different functions, they are all involved in the control of metabolism and, more particularly, in glucose homeostasis.

Answer 345

Insulin: Protein consisting of 2 chains; designated A and B, that are connected by 2 disulfide bridges. Of the domestic species, feline insulin is most similar to bovine insulin, and canine insulin is similar to human insulin, and identical to procine insulin in its amino acid structure.

Answer 346

The synthesis of insulin is biphasic: an acute phase involves the release of preformed insulin, and a chronic phase involves the synthesis of protein. The synthesis of insulin begins with the formation of a linear polypeptide preproinsulin within the rough endoplasmatic reticulum. A small peptide fragment is removed to form proinsulin. Proinsulin is coiled, and the end fragments are joined by disulfide bonds. Proinsulin is transferred to the Golgi apparatus, where it is further processed and packaged into granules that contain both insulin and the connecting or C peptide.

Answer 347

The secretion of insulin follows biphasic kinetics in response to appropriate stimuli. The initial, acute release of insulin involves the exocytosis of preformed insulin from secretion granules. After the acute phase, a chronic phase of secretion occurs that involves the synthesis of protein and, hence, probably the synthesis of insulin.

Answer 348

Insulin is metabolize mainly by the liver and kidneys. The metabolism of insulin involves splitting the A and B chains and reducing the chains to amino acids and peptides. The half life of insulin is about 10 minutes.

Answer 349

The main metabolic functions of insulin are anabolic. Insulin acts at a number of sites within the metabolic pathways of carbohydrates, fats, and proteins. It is important to realize that the liver is an especially important target organ, in part because the pancreatic venous effluent passes directly to the liver. The net effect of the actions of insulin is to lower blood concentrations of glucose, fatty acids, and amino acids and to promote intracellular conversion of these compounds to their storage forms (i.e., glycogen, triglycerides, and protein, respectively).

Answer 350

Glucose does not readily penetrate cell membrane except in a few tissues, such as brain, liver, and red and white blood cells, all of which must have continual access to glucose.

Answer 351

The presence of insulin is critical to the movement of glucose through the plasma membrane into the cell.

Answer 352

Insulin has profound effects on carbohydrate metabolism. Insulin facilitates the use of glucose; namely glycolysis, which involves the oxidation of glucose to pyruvate and lactate through the induction of enzymes; such as glucokinase, phosphofructokinase, and pyruvate kinase. Insulin promotes glycogen production in the liver, in adipose tissue, and in skeletal muscle by increasing glycogen synthetase activity with a concomitant decrease in glycogen phosphorylase activity.

Answer 353

Gluconeogenesis is decreased by insulin because of the promotion of protein synthesis in peripheral tissues, thereby decreasing the amount of amino acids available for gluconeogenesis. In addition, insulin decreases the activity of hepatic enzymes that are involved in the conversion of amino acids to glucose.

Answer 354

In adipose tissue; insulin promotes the synthesis of triglycerides by facilitating the intracellular use of glucose; resulting in increased levels of pyruvate: a precursor of acetyl-coenzyme A (CoA), which in turn is a precursor of fatty acids. Insulin also decreases lipolysis in adipose tissue.

Answer 355

Insulin promotes uptake of amino acids by most tissue, including skeletal muscle, but not liver. Insulin promotes protein synthesis, and inhibits protein degradation = promotes maintenance of a positive nitrogen balance. With insulin deficiency; protein catabolism increases, with increased amounts of amino acids available for hepatic gluconeogenesis, and a resultant increase in the blood glucose concentration.

Answer 356

The most important factor I the control of insulin secretion is the conc of blood glucose: positive feedback system. Increased conc of blood glucose initiate the synthesis and release of insulin by the β cells of the pancreatic islets. A numer of GI hormones, including gastrin, cholecystokinin, secretin, and gastric inhibitory peptide, stimulate insulin secretion. The presence of amino acids and fatty acids in the intestinal tract also stimulates the release of insulin, although with less potency than that of glucose.

Answer 357

Glucagon from the α cells of the pancreas has a direct stimulatory effect on the β cells to secrete insulin. Conversely, somatostatin inhibits the secretion of insulin. Both hormones work through the adenyl cyclase system; glucagon being stimulatory, and somatostatin being inhibitory.

Answer 358

Catecholamines (mainly epinephrine) tend to decrease insulin secretion through an interation with the α-adrenergic receptors on the β cells. The pancrease also has cholinergic innervation by the automonic nervous system, and, in contrast to adrenergic stiulation, cholinergic activity increases insulin secretion through the release of acetylcholine.

Answer 359

1) decreased uptake of glucose by body tissues, 2) increased glycogenolysis, and 3) increased gluconeogenesis. The latter occurs as a result of increased hepatic gluconeogenesis caused by increased availability of amino acids, which occurs as a result of increased protein catabolism.

Answer 360

Diuresis or polyuria.

Answer 361

Increased metabolism of triglycerides leads to increased conc of fatty acids in the blood and the formation of ketone bodies in the liver. Insulin deficiency increases lipolysis and, as a result, increases the level of free fatty acids in the blood. The fatty acids are oxidized by the liver to form acetyl-CoA, which can be further converted to acetoacetate, β-hydroxybutyrate, and acetone; collectively called ketone bodies. The ketone bodies are acidic anions, and their presence produces acidosis because of the depletion of bicarbonate ions.

Answer 362

The ketone bodies are acidic anions, and their presence produces acidosis because of the depletion of bicarbonate ions.

Answer 363

Protein hormone (polypeptide) produced by the α cells of the islets of Langerhans. The stomach produces a molecule called gut glucagon, that is identical to the pancreatic glucagon molecule, and the small intestine produces an immunologically similar molecule called glicentin.

Answer 364

Glucagon has a close relationship with insulin in the control of glucose metabolism. Like other polypeptide hormones; glucagon is first synthesized in the ER as part of a precursor molecule, packaged in the Golgi apparatus, and final processing occurs in the secretory granules. Glucagon is released by exocytosis. Metabolized mainly by the liver and kidneys. Half-life in plasma of ca 5 min.

Answer 365

Glucagon increases cAMP production in the liver, which leads to the most important functions of glucagon: decreased glycogen synthesis, increased glycogenolysis, and increased gluconeogenesis: the net result is an increase in glucose conc in the blood.

Answer 366

The physiologic actions of glucagon are opposite (counterbalance) those of insulin; most of the effect of glucagon is centered on the liver. Consumption of food---increased insulin secretion---conservation of energy through the formation of storage forms of carbohydrates, fats, and proteins. Glucagon secretion, which begins with the ingestion of food, increases as the interval from food ingestion lengthens and blood glucose conc begins to decline. = preserved postprandial hypoglycemia

Answer 367

Glucagon synthesis and release is stimulated by decreased plasma glucose conc. = negative feedback system. Insulin and glucagon work in tandem to maintain glucose conc within the physiologic range. Because the α cells require insulin for glucose entry into the cells (as do most cells), in clinical syndromes involving insulin insufficiency (diabtes mellitus), glucose entry into the α cells is reduced, and plasma glucagon conc are paradoxically elevated. Glucagon promotes lipolysis and an increase in fatty acids, which has a negative feedback effect on glucagon secretion

Answer 368

Protein ingestion represents an exception to the rule of opposite responses of glucagon and insulin. The release of insulin and glucagon in response to protein ingestion appears logical; increased insulin secreted in response to increased plasma amino acid levels, leads to lower glucose conc, and increased glucagon would counteract this through increased hepatic gluconeogenesis; resulting in maintenance of blood glucose within normal limits. The complementary responses of insulin and glucagon allow growth to occur I animals fed a diet of protein and fat only.

Answer 369

Intestinal hormones, with the exception of secretin, stimulate both glucagon and insulin secretion. A similar (inhibitory) response to somatostatin is observed for both glucagon and insulin. Both sympathetic and parasympathetic stimulation of the autonomic nervous system induce secretion of glucagon.

Answer 370

Somatostatin: Molecule identified in the brain, the GI tract and the D cells of the pancreatic islets. Its synthesis and secretion are similar to those observed for other protein hormones. Mainly metabolized in the liver and kidney.

Answer 371

The main functions of somatostatin are to inhibit the secretion of hormones produced by the pancreas (insulin, glucagon, pancreatic polypeptide)= inhibitory actions by regulating of all the endocrine cells of the pancreas (including the D cells). Pancreatic somatostatin inhibits the digestive processes by decreasing nutritive absorption and digestion. The motility and secretory activity of the GI tract are decreased by somatostatin. The α cells are more affected than the β cells: glucagon secretion more affected.

Answer 372

Somatostain secretion is increased by nutrients such as glucose and amino acids, and by the neurotransmitters of the autonomic nervous system; epinephrine, norepinephrine and acetylcholine. Of the hormones produced by the pancreas, only glucagon stimulates somatostatin secretion.

Answer 373

Pancreatic Polypeptide: Produced by the F cells of the pancreas. The effects are directed toward the GI tract- The secretion of pancreatic enzymes and the contraction of the gallbladder are inhibited by the actions of this hormone. Both gut motility and gastric emptying are increased by the action of pancreatic polypeptide.

Answer 374

The secretion is stimulated by intestinal hormones, including cholecystokinin, secretin, and gastrin. Stimulation of the vagus nerve also promotes pancreatic polypeptide secretion. Ingestion of protein is stimulatory for secretion, whereas carbohydrates and fats have little effects. Somatostatin inhibits pancreatic polypeptide secretion.

Answer 375

Insulin-Secreting Islet Cell Neoplasia Insulinoma is uncommon in the dog and rare in the cat.

Answer 376

Insulin-secreting beta-cell neoplasia is the most common islet-cell neoplasia in the dog, perhaps because beta cells comprise approximately 70% of cells in the islets of Langerhans.

Answer 377

Most canine insulinomas are malignant. The most common sites of metastases are regional lymph nodes and the liver, although metastatic disease is possible anywhere. Although the etiology of insulinoma is not known, local growth hormone production, which is not associated with elevated plasma growth hormone concentration, has been documented in primary and metastatic canine insulinoma lesions.

Answer 378

The most important compensatory mechanisms for hypoglycemia are inhibition of insulin secretion and stimulation of counterregulatory hormones secretion.

Answer 379

Glucose is the primary regulator of insulin secretion. When glucose enters beta-pancreatic cells, it is metabolized to ATP and closes ATP-sensitive K+ channels. Closure of these K+ channels decreases K+ efflux and results in depolarization of the beta cell and opening of voltage-sensitive Ca+2 channels. Increased cytoplasmic Ca+2 concentration results in insulin exocytosis. In a normal animal, insulin secretion is completely inhibited when blood glucose is less than 80 mg/dL. However, insulin secretion from neoplastic beta cells is independent of blood glucose concentration and persists despite low blood glucose concentration. Therefore, one of the hallmarks of insulinoma is high or normal blood insulin concentration despite low blood glucose concentration.

Answer 380

The four counterregulatory hormones secreted in response to hypoglycemia are glucagon, catecholamines, growth hormone, and glucocorticoids. Of these hormones, glucagon and catecholamines are most important in elevating blood glucose concentration.

Answer 381

Most clinical signs are due to the effect of hypoglycemia on the central nervous system (neuroglycopenia), or to hypoglycemia-induced release of catecholamines. Glucose is the single most important source of energy in the brain, and carbohydrate storage in neural tissue is limited. Therefore, brain function depends on a continuous supply of glucose.

Answer 382

Clinical signs attributable to neuroglycopenia include seizures, collapse, weakness, ataxia, disorientation, mental dullness, and visual disturbances. Clinical signs related to excess catecholamine release and stimulation of the sympathetic nervous system include tremors, hunger, and nervousness. Severity of clinical signs increases as blood glucose decreases. Severe hypoglycemia can ultimately result in coma and death. Clinical signs may also be related to the duration and rate in which hypoglycemia develops because a gradual decrease in blood glucose concentration may be less likely to stimulate catecholamine secretion.

Answer 383

Occasionally, clinical signs are episodic because secretion of counterregulatory hormones elevates blood glucose concentration and temporarily resolves neuroglycopenic clinical signs.

Answer 384

Physical examination is unremarkable in most dogs with insulinoma. Dogs may be overweight due to the anabolic effects of insulin, and postictal findings may be apparent if a dog recently had a seizure. A peripheral polyneuropathy characterized by tetraparesis and decreased or absent appendicular reflexes has been described.

Answer 385

Differential diagnoses for hypoglycemia may be divided into those associated with excess secretion of insulin or insulin-like factors, decreased glucose production, excess glucose consumption, drug associated, or spurious causes.

Answer 386

Insulinoma, extrapancreatic tumor, or islet cell hyperplasia.

Answer 387

Hypoadrenocorticism, hypopituitarism, growth hormone deficiency, liver diseases, glycogen storage diseases, neonates, and toy breeds. Fasting, malnutrition, or pregnancy may also result in hypoglycemia. Excess glucose consumption may develop in sepsis or extreme exercise.

Answer 388

Therapy for insulinoma can be divided into treatment of the acute hypoglycemic crisis and long-term management. During an acute hypoglycemic crisis dextrose can be given as a slow bolus .The bolus is followed by an IV continuous rate infusion (CRI) of dextrose. In severe cases the animal may have to be sedated with diazepam or pentobarbital for several hours while this treatment is continued and until seizures resolve. Cerebral hypoxia may lead to cerebral edema, and if cerebral edema is suspected it can be treated with mannitol and furosemide A CRI of glucagon has been reported in one dog with insulinoma-associated hypoglycemia. Glucagon increases blood glucose concentration by promoting glycogenolysis and gluconeogenesis. However, glucagon also increases insulin secretion and animals should be monitored carefully for the possibility of worsening hypoglycemia.

Answer 389

By increasing gluconeogenesis, elevating glucose 6-phosphatase activity, decreasing blood glucose uptake into tissue, and stimulating glucagon secretion. Glucocorticoids can be administered intravenously during an acute hypoglycemic crisis in the form of dexamethasone or can be given orally once a dog is stable.

Answer 390

Canine Diabetes Mellitus The endocrine pancreas is composed of the islets of Langerhans, which are dispersed as “small islands” in a “sea” of exocrine-secreting acinar cells. Four distinct cell types have been identified within these islets on the basis of staining properties and morphology: alpha cells, which secrete glucagon; beta cells, which secrete insulin; delta cells, which secrete somatostatin; and F cells, which secrete pancreatic polypeptide. Dysfunction involving any of these cell lines ultimately results in either an excess or a deficiency of that respective hormone. In the dog, the most common disorder of the endocrine pancreas is diabetes mellitus, which results from an insulin deficiency caused by destruction of beta cells.

Answer 391

Insulin-dependent diabetes mellitus (IDDM). At the time diabetes mellitus is diagnosed, virtually all dogs have insulin-dependent disease.

Answer 392

Permanent hypoinsulinemia and an absolute necessity for exogenous insulin to maintain glycemic control.

Answer 393

A reduction in the number and size of pancreatic islets, a decrease in the number of beta cells within islets, and beta-cell vacuolation and degeneration. In some dogs, an extreme form of the disease may occur, represented by a congenital absolute deficiency of beta cells and pancreatic islet hypoplasia or aplasia. Less severe changes of pancreatic islets and beta cells may predispose the adult dog to diabetes mellitus after it has been exposed to environmental factors, such as insulin-antagonistic diseases and drugs, obesity, and pancreatitis.

Answer 394

Glutamic acid decarboxylase (GAD)

Answer 395

Interestingly, development of insulin autoantibodies does not seem to be a common feature of the disease in dogs. Seemingly, autoimmune mechanisms, in conjunction with genetic and environmental factors, insulin-antagonistic diseases and drugs, obesity, and pancreatitis all play a potential role in the initiation and progression of diabetes in dogs.

Answer 396

Polyuria, polydipsia, polyphagia, and weight loss.

Answer 397

Ketoacidosis develops as the production of ketone bodies increases to compensate for underutilization of blood glucose.

Answer 398

Loss of beta-cell function is irreversible in IDDM dogs, and lifelong insulin therapy is mandatory to maintain glycemic control of the diabetic state.

Answer 399

Clinical recognition of type 2 or non-insulin-dependent diabetes mellitus (NIDDM) is uncommon to rare in the dog and is usually associated with a concurrent insulin antagonistic disease or drug. Transient or reversible diabetes is extremely uncommon in dogs and usually occurs in dogs with subclinical diabetes treated with insulin antagonistic drugs (e.g., glucocorticoids) or in the early stages of an insulin-antagonistic disorder (e.g., diestrus in females, hyperadrenocorticism). Such dogs have a reduced but adequate mass of functional beta cells to maintain carbohydrate tolerance when insulin resistance is not present, but they are unable to secrete an adequate amount of insulin to maintain euglycemia in the presence of insulin antagonism. Early recognition and correction of insulin antagonism may reestablish euglycemia without the long-term need for insulin therapy. Failure to quickly correct the insulin antagonism will result in progressive loss of beta cells and the eventual development of IDDM.

Answer 400

Diabetes mellitus results from a relative or absolute deficiency of insulin secretion by the beta cells. Insulin deficiency, in turn, causes decreased tissue utilization of glucose, amino acids, and fatty acids, accelerated hepatic glycogenolysis and gluconeogenesis, and accumulation of glucose in the circulation, causing hyperglycemia.

Answer 401

As the blood glucose concentration increases, the ability of the renal tubular cells to resorb glucose from the glomerular ultrafiltrate is exceeded, resulting in glycosuria. In dogs, this typically occurs when blood glucose concentrations exceed 180 to 220 mg/dL. Glycosuria creates an osmotic diuresis with compensatory polyuria and, in turn, polydipsia. Diminished peripheral tissue utilization of ingested glucose results in weight loss as the body attempts to compensate for perceived “starvation.”

Answer 402

The interaction of the “satiety center” in the ventromedial region of the hypothalamus with the “feeding center” in the lateral region of the hypothalamus is responsible for controlling the amount of food ingested.The feeding center, responsible for evoking eating behavior, continuously functions but can be transiently inhibited by the satiety center after food ingestion. The amount of glucose entering the cells in the satiety center directly affects the feeling of hunger; the more glucose that enters these cells, the less the feeling of hunger and vice versa. The ability of glucose to enter the cells in the satiety center is mediated by insulin. In diabetics with a relative or absolute lack of insulin, glucose does not enter satiety center cells, resulting in failure to inhibit the feeding center. Thus, these individuals become polyphagic despite hyperglycemia.

Answer 403

The four classic signs of diabetes mellitus are polyuria, polydipsia, polyphagia, and weight loss. Occasionally an owner presents a dog because of sudden blindness caused by cataract formation. If the clinical signs associated with uncomplicated diabetes are not observed by the owner, a diabetic dog is at risk for developing systemic signs of illness (i.e., lethargy, anorexia, vomiting, weakness) as progressive ketonemia and metabolic acidosis develop.

Answer 404

Untreated diabetics may ultimately develop diabetic ketoacidosis (DKA), systemic signs of illness, and potentially life-threatening derangements in fluid and acid/base balance.

Answer 405

It is important to document both persistent hyperglycemia and glycosuria to establish a diagnosis of diabetes mellitus, because hyperglycemia differentiates diabetes mellitus from primary renal glycosuria, whereas glycosuria differentiates diabetes mellitus from other causes of hyperglycemia. Documenting an increase in the serum fructosamine concentration supports the presence of sustained hyperglycemia; however, a serum fructosamine concentration in the upper reference range can occur in symptomatic diabetic dogs if the diabetes developed shortly before presentation.

Answer 406

Shortly after consuming large quantities of easily digestible carbohydrates; quite rarely in “stressed,” hyperactive, or extremely nervous dogs; in the early stages of development of diabetes mellitus (i.e., subclinical diabetes); and with disorders and drugs causing insulin resistance, most notably hyperadrenocorticism, glucocorticoids, and during diestrus in intact females.

Answer 407

A thorough clinicopathologic evaluation is recommended once the diagnosis of diabetes mellitus has been established. The clinician must be aware of any disease that might be causing or contributing to carbohydrate intolerance (e.g., hyperadrenocorticism), that may result from carbohydrate intolerance (e.g., infection), or that may force modification of therapy (e.g., pancreatitis). Serum progesterone concentration should be determined if diabetes mellitus is diagnosed in an intact female, regardless of her cycling history.

Answer 408

Once the diagnosis of diabetes is established, dogs should be considered to have IDDM and treatment with insulin should be initiated. Initially, intermediate-acting insulin (i.e., NPH, lente) is the choice for establishing control of glycemia in diabetic dogs. Recombinant human or pork source insulin should be used to minimize development of antiinsulin antibodies, which may interfere with control of glycemia. Insulin therapy is begun with recombinant human NPH or pork lente insulin at an approximate dosage of 0.25 U/kg twice a day.

Answer 409

Correction of obesity and increasing dietary fiber content are the two most beneficial steps that can be taken to improve control of glycemia. Diets containing increased fiber content have the potential benefit of improving glycemic control in diabetics. Fiber can form a viscous gel on the absorptive surface of the intestine that impairs convective transfer of glucose and water from the lumen to the blood supply, thus slowing intestinal glucose absorption. The more viscous soluble fibers (e.g., gums, pectin) slow glucose diffusion to a greater degree than the less viscous insoluble fibers (e.g., lignin, cellulose) and, as such, are believed to be of greater benefit in improving control of glycemia.

Answer 410

As a result of decreased number of insulin receptors at the surface of the cell membrane, alterations in insulin receptor binding affinity, or impairment in one of several postreceptor steps responsible for activation of glucose transport systems. Some causes of insulin resistance are readily apparent at the time diabetes is diagnosed, such as obesity and the administration of insulin-antagonistic drugs. Other causes of insulin resistance may not be readily apparent, requiring additional diagnostic evaluation to be identified. In general, any concurrent inflammatory, infectious, cardiac, hormonal, or neoplastic disorder can cause insulin resistance and interfere with insulin effectiveness. Identification and treating concurrent disease is integral to successfully managing diabetes.

Answer 411

The need to maintain near-normal blood glucose concentrations is not necessary in diabetic dogs. Most owners are happy and most dogs are healthy and relatively asymptomatic if most blood glucose concentrations are kept between 100 and 250 mg/dL.

Answer 412

Fructosamines are glycated proteins that are synthesized from an irreversible, nonenzymatic, insulin-independent binding of glucose to serum proteins. Serum fructosamine concentrations are a marker of mean blood glucose concentration during the circulating protein lifespan. Depending on the protein, lifespan varies from 1 to 3 weeks. Serum fructosamine concentrations increase when glycemic control of the diabetic dog worsens and decrease when glycemic control improves.

Answer 413

Serum fructosamine concentration can be affected by hypoalbuminemia (150 mg/dL).

Answer 414

It is preferred to adjust insulin therapy based on interpretation of a single serial blood glucose curve, with the ideal goal to maintain the blood glucose concentration between 100 and 250 mg/dL. Variables such as the actual amount of insulin drawn into the syringe and subsequently absorbed from the subcutaneous site of deposition and the interaction among insulin, diet, exercise, stress, excitement, presence of concurrent disorders, and secretion of the counterregulatory hormones (i.e., glucagon, epinephrine, cortisol, growth hormone) change with time and affect the reproducibility of serial blood glucose curves.

Answer 415

Hyperglycemia induced by stress, aggression, or excitement is the single biggest problem affecting accuracy of the serial blood glucose curve.

Answer 416

Secretion of glucagon, epinephrine, cortisol, and growth hormone

Answer 417

Hyperglycemia presumably develops as a result of increased catecholamine and glucocorticoid secretion and increased hepatic glucose production. Stress hyperglycemia can significantly increase blood glucose concentrations in diabetic dogs despite the administration of insulin; an effect which has serious consequences on the clinician's ability to accurately judge the effectiveness of the insulin injection. Failure to recognize the effect of stress on blood glucose results may lead to the erroneous perception that the diabetic dog is poorly controlled. In such a situation, insulin dose is often increased and repetition of this cycle eventually culminates in induction of the Somogyi response, clinically apparent hypoglycemia, or referral for evaluation of insulin resistance.

Answer 418

The most common problems with the insulin treatment regimen in the dog include insulin under dosage, induction of the Somogyi response, short duration of lente insulin effect, and once-daily insulin administration.

Answer 419

Control of glycemia can be established in most dogs using less than 1.0 U of insulin/kg of body weight administered twice each day. An inadequate dose of insulin in conjunction with once-daily insulin therapy is a common cause for persistence of clinical signs. Other causes for insulin ineffectiveness (most notably the Somogyi response) should be considered once the insulin dosage exceeds 1.0 to 1.5 units/kg/injection, the insulin is being administered every 12 hours, and control of glycemia remains poor.

Answer 420

The Somogyi response is insulin-induced hypoglycemia, which leads to counterregulation and severe hyperglycemia. This is a normal physiologic response to impending hypoglycemia induced by excessive insulin. When the blood glucose concentration declines to less than 65 mg/dL or when the blood glucose concentration decreases rapidly regardless of the glucose nadir, direct hypoglycemia-induced stimulation of hepatic glycogenolysis and secretion of diabetogenic hormones, most notably glucagon and epinephrine, increase the blood glucose concentration, minimize signs of hypoglycemia, and cause marked hyperglycemia within 12 hours of glucose counter regulation. T he marked hyperglycemia that follows hypoglycemia is due, in part, to an inability of the diabetic dog to secrete sufficient endogenous insulin to dampen the rising blood glucose concentration. By the next morning, the blood glucose concentration can be extremely elevated (400 to 800 mg/dL) and the morning urine glucose concentration is consistently 1 to 2 g/dL as measured with urine glucose test strips.

Answer 421

Unrecognized short duration of insulin effect combined with insulin dose adjustments based on morning urine glucose concentrations. The Somogyi response is often suspected in poorly controlled diabetic dogs whose insulin dosage is approaching 2.2 U/kg body weight per injection but can also occur at insulin dosages less than 0.5 U/kg/injection. Induction of the Somogyi response typically leads to high insulin doses as the veterinarian reacts to the persistence of clinical signs, absence of clinical hypoglycemia, and high blood glucose and serum fructosamine concentrations by increasing the insulin dose and perpetuating the problem.

Answer 422

Hypoglycemia (300 mg/dL) following insulin administration. The Somogyi response should also be suspected when the blood glucose concentration decreases rapidly regardless of the glucose nadir (e.g., a drop from 400 to 100 mg/dL in 2 to 3 hours). Secretion of diabetogenic hormones during the Somogyi response may induce insulin resistance, which can last 24 to 72 hours after the hypoglycemic episode. If a serial blood glucose curve is obtained on the day glucose counterregulation occurs, hypoglycemia will be identified and the diagnosis established. Establishing the diagnosis may require several days of hospitalization and serial blood glucose curves, an approach that eventually leads to problems with stress-induced hyperglycemia. A preferred alternative approach is to arbitrarily reduce an insulin dose 1 to 5 units and have the owner evaluate the dog's clinical response over the ensuing 2 to 5 days. If clinical signs of diabetes worsen following a reduction in the insulin dose, another cause for the insulin ineffectiveness should be pursued..

Answer 423

For most dogs, the duration of effect of lente and NPH insulin is 10 to 14 hours and twice-a-day insulin administration is effective in controlling blood glucose concentrations. However, in some diabetic dogs, the duration of effect of lente and NPH insulin is less than 10 hours. As a result, significant hyperglycemia (>300 mg/dL) occurs for several hours each day and owners of these dogs usually mention continuing problems with persistence of clinical signs. (more common that the owners report problems when the animal is hyperglycemic compared to when hypoglycemic.

Answer 424

In some diabetic dogs, the duration of effect of NPH or lente insulin is greater than 12 hours and twice-daily insulin administration creates problems with hypoglycemia and the Somogyi response. Gradually decreasing blood glucose concentrations measured at the time of sequential insulin injections is another indication of prolonged duration of insulin effect. The effectiveness of insulin in lowering the blood glucose concentration is variable from day to day, presumably because of varying concentrations of diabetogenic hormones whose secretion was induced by prior hypoglycemia.

Answer 425

chronic inflammation of the subcutaneous tissues induced by chronic injection of insulin in the same area of the body.

Answer 426

Species of origin of the injected insulin, insulin formulation, impurities in the preparation, and method of injection influence development of antiinsulin antibodies. Dogs treated with recombinant human and pork source insulin have more stable control of glycemia for extended periods of time, compared with dogs treated with beef source insulin. Documentation of serum insulin antibodies should utilize assays that have been validated in diabetic dogs. Switching the source of insulin, switching to a purer form of insulin (i.e., regular crystalline insulin), or both should be considered if insulin antibodies are identified in a poorly controlled diabetic dog.

Answer 427

From problems occurring before the interaction of insulin with its receptor (e.g., insulin-binding antibodies), at the receptor (e.g., altered insulin receptor binding affinity or concentration), or at steps distal to the interaction of insulin and its receptor. Postreceptor problems are difficult to differentiate clinically from receptor problems, and both often coexist.

Answer 428

Obesity, inflammation (such as occurs with pancreatitis or gingivitis), a disorder causing excessive secretion of a potentially insulin-antagonistic hormone (such as cortisol), or a disorder that causes a deficiency of hormone necessary for insulin action (such as thyroid hormone).

Answer 429

Failure of the blood glucose concentration to decrease below 300 mg/dL during a serial blood glucose curve is suggestive of but not definitive for the presence of insulin resistance. An insulin resistance-type blood glucose curve can also result from stress-induced hyperglycemia, the Somogyi response, and other problems with insulin therapy and a decrease in the blood glucose concentration below 300 mg/dL can occur with disorders causing relatively mild insulin resistance. Serum fructosamine concentrations are typically greater than 500 µmol/L in animals with insulin resistance and can exceed 700 µmol/L if resistance is severe.

Answer 430

Severe obesity, use of diabetogenic drugs (glucocorticoids), hyperadrenocorticism, diestrus, chronic pancreatitis, renal insufficiency, oral and urinary tract infections, hyperlipidemia, and antiinsulin antibodies in dogs receiving beef source insulin.

Answer 431

blindness and anterior uveitis resulting from cataract formation; diabetic retinopathy (retinal hemorrhage, microaneurysms); chronic pancreatitis; recurring infections; hypoglycemia; and ketoacidosis.

Answer 432

Cataract formation is the most common chronic complication of diabetes mellitus in the dog. The pathogenesis of diabetic cataract formation is thought to be related to altered osmotic relationships in the lens induced by the accumulation of sorbitol and fructose, sugars that are potent hydrophilic agents that cause an influx of water into the lens, leading to swelling and rupture of the lens fibers and the development of cataracts. Cataract formation is an irreversible process once it begins, and it can occur quite rapidly. Vision is restored in 80% to 90% of diabetic dogs that undergo cataract removal.

Answer 433

During embryogenesis, the lens is formed within its own capsule and its structural proteins are not exposed to the immune system. Therefore, immune tolerance to the crystalline proteins does not develop. During cataract formation and reabsorption, lens proteins can be exposed to local ocular immune systems, resulting in inflammation and uveitis.

Answer 434

Although a common complication in diabetic cats, diabetic neuropathy is infrequently recognized in dogs. Diabetic neuropathy in dogs is primarily distal, characterized by segmental demyelination and remyelination, as well as axonal degeneration and regeneration. Subclinical neuropathy is more common than is severe neuropathy resulting in clinical signs.

Answer 435

proteinuria, primarily albuminuria, as a result of the glomerular dysfunction. As the glomerular changes progress, glomerular filtration becomes progressively impaired, resulting in the development of azotemia and eventually uremia. With severe fibrosis of the glomeruli, oliguric and then anuric renal failure develops.

Answer 436

Unlike dogs, cats are prone to stress hyperglycemia, which may render diagnosis and evaluation of in-hospital glucose measurements difficult. Cats often suffer from a type of diabetes in which residual β-cell function is present, allowing disease remission with early treatment; and because cats are true carnivores, choosing the appropriate diet may have a positive effect on the course of the disease.

Answer 437

Unlike diabetic dogs, type 1–like diabetes mellitus seems to be rare in the cat. Antibodies against β cells and insulin have not been demonstrated in cats, and lymphocytic infiltration, as a marker of immune-mediated destruction, has only been described in a small number of diabetic cats.

Answer 438

It is assumed that approximately 80% of diabetic cats suffer from a type 2–like diabetes mellitus, although there are little data to support this. Nevertheless, most endocrinologists would agree that a type 2–like diabetes mellitus is the most frequent form in cats. Similar to human type 2 diabetes mellitus, feline type 2 diabetes mellitus is a heterogeneous disease attributable to a combination of impaired insulin action in liver, muscle, and adipose tissue (insulin resistance) and β-cell failure.

Answer 439

........................four times higher in Burmese cats than in domestic cats. Major risk factors for the development of diabetes mellitus in cats are increasing age, male gender, being neutered, physical inactivity, glucocorticoid and progestin administration, and obesity.

Answer 440

Glucose homeostasis is maintained by a complex system of regulating and modulating hormones and factors, the most important of which is insulin. Insulin is the only hormone capable of decreasing blood glucose levels. Insulin synthesis starts in the rough endoplasmatic reticulum with the formation of preproinsulin, which is then converted to proinsulin by removal of a small peptide fragment. Proinsulin is further processed to insulin in the Golgi apparatus by removing another peptide, called C-peptide (connecting peptide). Insulin and C-peptide are packed and stored in secretory granules and released in equimolar amounts by the process of exocytosis.

Answer 441

Mainly metabolized by the liver and the kidneys. Continuous availability of insulin and moment-to-moment adjustments are crucial for normal carbohydrate, protein, and lipid metabolism. The body exhibits complex mechanisms to ensure adequate basal insulin secretion between meals, as well as increased insulin secretion after a meal. The most important regulator is the glucose concentration in blood, and there is a positive feedback mechanism between the blood glucose concentration and the insulin secretion rate.

Answer 442

Glucose is transported into β cells via the glucose transporter protein GLUT2, which allows rapid equilibration of extracellular and intracellular glucose concentrations. Glucose is metabolized (phosphorylation by glucokinase and production of pyruvate) within the β cells to produce ATP. Increase in the ATP/ADP ratio is followed by the closure of ATP-sensitive potassium channels in the β-cell membrane, preventing potassium ions from leaving the β cell. This in turn causes membrane depolarization and opening of voltage-dependent calcium channels in the membrane. The increase in cytosolic calcium then triggers insulin release.

Answer 443

Oral glucose induces more pronounced insulin secretion than glucose given IV. This phenomenon is due to the actions of so-called incretin hormones, the most important being glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide, previously called gastric inhibitory polypeptide (GIP). Incretins are secreted by endocrine cells in the gastrointestinal tract in response to nutrients. They are then carried in the bloodstream to the pancreatic islets, where they interact with specific β-cell receptors to amplify insulin secretion. In addition to glucose and other sugars, amino acids and fatty acids are also stimulators of insulin secretion; stimulation may be direct or potentiated by incretins.

Answer 444

The autonomous nervous system also modulates islet hormone release In general terms, secretion of insulin is stimulated by vagal nerve fibers and inhibited by sympathetic nerve fibers. Several other pancreatic and extrapancreatic hormones, such as IAPP, glucagon, somatostatin, cortisol, and growth hormone, affect insulin secretion directly or indirectly.

Answer 445

Insulin is the most important anabolic hormone and it prevents catabolism of nutrient stores. Its main function is to ensure storage of glucose as glycogen, amino acids as protein, and fatty acids as fat. The primary target tissues for insulin are liver, muscle, and fat. Insulin facilitates the oxidation of glucose to pyruvate and lactate through the induction of enzymes, such as glucokinase, some hexokinases, phosphofructokinase, and pyruvate kinase.

Answer 446

Insulin promotes glycogen synthesis in liver, adipose tissue, and muscle by increasing glycogen synthetase activity. Gluconeogenesis is decreased by insulin because of the promotion of protein synthesis in peripheral tissues, thus decreasing the amount of amino acids available for gluconeogenesis. Additionally, insulin decreases the activity of hepatic enzymes that are involved in the conversion of amino acids to glucose.

Answer 447

In adipose tissue, insulin promotes lipid synthesis and inhibits their degradation. Insulin activates the enzymes pyruvate dehydrogenase and acetyl-CoA carboxylase, which promote the synthesis of fatty acids from acetyl-CoA. Insulin also increases the activity of lipoprotein lipase, an enzyme that is located in the endothelium of capillaries of extrahepatic tissues and promotes the entry of fatty acids into adipose tissue. Inhibition of lipolysis is mediated through the inhibition of the enzyme hormone-sensitive lipase.

Answer 448

Insulin activates the enzymes pyruvate dehydrogenase and acetyl-CoA carboxylase, which promote the synthesis of fatty acids from acetyl-CoA. Insulin also increases the activity of lipoprotein lipase, an enzyme that is located in the endothelium of capillaries of extrahepatic tissues and promotes the entry of fatty acids into adipose tissue. Inhibition of lipolysis is mediated through the inhibition of the enzyme hormone-sensitive lipase.

Answer 449

Insulin stimulates protein synthesis and inhibits protein degradation, therefore promoting a positive nitrogen balance. Glucagon is the main antagonist of insulin. Glucagon acts predominantly on the liver, where it increases gluconeogenesis and glycogenolysis and decreases glycogen synthesis. It is also a ketogenic hormone because of its ability to enhance lipolysis.

Answer 450

Insulin and glucagon act in concert after ingestion of protein. Both hormones are released when the concentration of amino acids increases in the plasma. Insulin leads to a decrease in blood glucose concentration in concert with a decrease in amino acid levels. Glucagon counterbalances the decrease in glucose concentration by stimulation of hepatic gluconeogenesis. This interaction allows growth and survival with diets containing almost exclusively protein and fat.

Answer 451

Hyperglycemia develops when insulin secretion is absent or inadequate for the degree of insulin resistance. Absolute or relative lack of insulin has profound effects on carbohydrate, fat, and protein metabolism. Hyperglycemia results, in part, from reduced glucose entry into muscle, adipose tissue, and liver. Intestinal absorption of glucose and glucose entry into brain, kidney, and erythrocytes are not affected. The second and perhaps most important cause of hyperglycemia is unopposed glucose production in the liver (by gluconeogenesis and glycogenolysis). Glucagon contributes to increased production of glucose, as do other (stress) hormones.

Answer 452

When the renal capacity for glucose reabsorption is exceeded, glucose is lost in the urine. The resulting osmotic diuresis is compensated by increased water intake, which may lead to severe polydipsia. Diabetic polyphagia is regulated by central mechanisms, in which ghrelin-signaling and other pathways are important.

Answer 453

Derangement of lipid metabolism plays a major role in the development of diabetes mellitus and its complications. The condition is sometimes regarded as a disease of lipid metabolism rather than carbohydrate metabolism. Intracellular deficits of glucose and lack of insulin lead to acceleration of lipid catabolism. Increased levels of NEFA are transported to the liver, where they undergo β-oxidation to produce acetyl-CoA, the amount of which may exceed the capacity for further oxidation. This results in a shift to ketone body production and may lead to the development of ketoacidosis. An increased hepatic concentration of fatty acids also results in enhanced hepatic synthesis of triglycerides and very-low-density lipoproteins (VLDLs). The consequences are hepatic steatosis and hyperlipidemia.

Answer 454

Protein metabolism shifts toward decreased protein synthesis and increased proteolysis. Increased availability of amino acids further accelerates hepatic gluconeogenesis. Consequences are negative nitrogen balance, loss of muscle mass, and possibly cachexia.

Answer 455

Polyuria, polydipsia (PU/PD), polyphagia, and weight loss. Additional signs may include lethargy and a dry, lusterless haircoat. Physical examination may reveal hepatomegaly due to diabetes-induced hepatic lipidosis. About 10% of diabetic cats have overt signs of diabetic neuropathy, which include hindlimb weakness, decreased ability to jump, and a plantigrade posture while standing or walking. In most cats, neurologic signs are restricted to the hindlimbs, although weakness of the front limbs and a palmigrade stance may also be seen in isolated cases. Difficulty walking and jumping may be the only presenting complaint in some cats in which the other more typical signs have been overlooked by the owners. Findings during neurologic evaluation include paraparesis, tetraparesis, abnormal tendon reflexes, and proprioceptive deficits. Irritability when touching or manipulating the feet may be present.

Answer 456

In cats with concurrent or underlying disease, such as pancreatitis, hyperadrenocorticism, or hypersomatotropism (acromegaly), additional or other more prominent signs may be present. If the clinical signs of so-called uncomplicated diabetes go unnoticed, the cat is at risk of developing complicated diabetes (diabetic ketoacidosis, hyperosmolar nonketotic syndrome). As the metabolic situation deteriorates, lethargy, anorexia, reduced water intake, vomiting, dehydration, and abdominal pain develop. Icterus is a frequent presenting sign in cats with ketoacidosis, due to severe hepatic lipidosis, pancreatitis, or pancreatic neoplasia causing extrahepatic cholestasis. DIAGNOSIS AND WORKUP

Answer 457

The vast majority of cats are not presented until blood glucose concentrations exceed the renal capacity for glucose reabsorption (≈15 mmol/L, 270 mg/dL). It is usually only at this stage of the disease that signs, such as PU/PD, polyphagia, and weight loss, become apparent. Glucosuria alone, however, is insufficient to diagnose diabetes because it may also occur with renal defects, certain drugs, and stress.

Answer 458

Fructosamine is the product of an irreversible reaction between glucose and the amino groups of plasma proteins. Based on the lifespan of plasma protein, it is generally assumed that fructosamine concentration reflects the mean blood glucose concentration of the preceding 1 to 2 weeks. In the vast majority of newly diagnosed diabetic cats, fructosamine levels are >400 µmol/L and may be as high as 1500 µmol/L. It seems most likely that diabetic cats with concurrent hypoproteinemia or hyperthyroidism would have normal fructosamine levels, which could be misleading. In the majority of situations, fructosamine is a helpful parameter to differentiate between stress- and diabetes-related hyperglycemia

Answer 459

In most cats, urine specific gravity is >1.020 and sporadic ketone bodies may be found even in uncomplicated cases. Approximately 50% of cats have mild to moderate proteinuria.

Answer 460

a certain degree of stabilization has been achieved with insulin therapy (see later).

Answer 461

Most diabetic cats do well when blood glucose concentrations are kept between a maximum of approximately 15 mmol/L and a nadir of 5 mmol/L (270 to 90 mg/dL).

Answer 462

At the University of Zurich, treatment is started with either Vetsulin/Caninsulin or insulin Glargine (Lantus). Frequency of administration is always BID. The initial dose in cats weighing ≤4 kg is 1 U/cat BID, and in cats weighing >4 kg it is usually 1.5 to 2.0 U/cat BID. In cats with a blood glucose concentration

Answer 463

Cats are metabolically adapted to use primarily protein and fat, and diets high in carbohydrate appear to be unfavorable. It has been shown that using a low-carbohydrate, high-protein diet results in better clinical control and increased rates of diabetic remission. According to our data at the University of Zurich, remission rates are 15% to 25% when diets with variable compositions are used but may increase to >50% when insulin therapy is combined with a high-protein, low-carbohydrate.

Answer 464

In contrast to acute hyperglycemia, which stimulates insulin secretion and glucose utilization, chronic hyperglycemia impairs the secretion of insulin and contributes to insulin resistance and thereby perpetuates the diabetic disease. These damaging effects of chronic hyperglycemia have been referred to as glucotoxicity

Answer 465

Today it is well accepted that good glycemic control improves pancreatic insulin response and partially corrects insulin secretion defects. It has been postulated by some researchers that the remission rate is higher in cats treated with insulin glargine (Lantus) than with other types of insulin. According to our own data generated during the past few years, it seems more likely that the increased remission rates are associated with the introduction of low-carbohydrate, high-protein diets than with a particular type of insulin.

Answer 466

Another potential acquired cause of β-cell dysfunction is lipotoxicity ( The concept of glucotoxicity (and possibly lipotoxicity) is important because immediate treatment of diabetes may reverse the negative effects of glucose and increase the chance of remission.

Answer 467

Cats are prone to stress hyperglycemia, which develops as a result of an increase in catecholamines or may be due to increased gluconeogenesis stimulated by lactate release in struggling cats. Stress-induced hyperglycemia not only renders diagnosis of diabetes difficult but also complicates the accurate evaluation of blood glucose concentrations measured during long-term management. Increases in blood glucose can range from mild to severe. Blood glucose levels may remain extremely elevated throughout the day despite insulin therapy or may start in an acceptable range and then steadily increase. Blood sampling can be extremely stressful for cats and is, therefore, a common cause of stress hyperglycemia.

Answer 468

Diabetic remission that goes unnoticed, sudden increase in insulin sensitivity due to cure or improvement of concurrent disorders, overly stringent glycemic control (i.e., too much insulin), inadvertent insulin overdose, long duration of insulin action when given BID resulting in excessive overlap (mainly with PZI or Insulin Glargine), and inappetence resulting in relative insulin overdose. Hypoglycemia may be a recurrent problem, most often seen in cats with concurrent disease in which phases of insulin sensitivity and insulin resistance alternate. Diabetic cats with chronic renal failure are notoriously difficult to regulate because insulin resistance due to uremic toxins coexists with reduced insulin clearance by the kidneys.

Answer 469

reduction or discontinuation of insulin, changing to an insulin with shorter duration of effect, and treatment of concurrent diseases.

Answer 470

Severe obesity, chronic renal failure, chronic pancreatitis, stomatitis/oral infections, hyperadrenocorticism, and hypersomatotropism (acromegaly). (Any inflammatory, infectious, neoplastic, and endocrine disorder can cause insulin resistance)

Answer 471

Hyperadrenocorticism and hypersomatotropism (acromegaly), although insulin resistance may also be mild or variable. Approximately 80% of cats with hyperadrenocorticism and nearly all cats with hypersomatotropism will develop diabetes mellitus.

Answer 472

Hypersomatotropism in cats is caused by a growth hormone (GH)-producing tumor (usually an adenoma) in the pars distalis of the pituitary gland.

Answer 473

GH has catabolic and anabolic effects; the anabolic are in part mediated by insulin-like growth factor-1 (IGF-1). The catabolic effects are mainly due to insulin antagonism and are the reason for the diabetes mellitus. The anabolic effects include proliferation of bone, cartilage, soft tissue, and organs resulting in a large body size, broad head and large paws, weight gain, prognathia inferior, respiratory difficulties because of thickening of pharyngeal tissues, degenerative arthropathy, and organomegaly with potential organ dysfunction. Growth of the tumor may lead to signs of CNS disease.

Answer 474

Acromegaly has long been considered a rare disorder. However, it was recently suggested that acromegaly occurs more frequently than previously thought and is most likely underdiagnosed. Because the availability of a validated GH assay for cats is inconsistent, diagnosis is usually based on the finding of high IGF-1 concentration. (IGF-1 concentrations are often low in newly diagnosed diabetic cats and increase markedly after initiating insulin therapy. IGF-1 may therefore be measured 6 to 8 weeks after initiating insulin therapy)

Answer 475

muscle contraction, nerve cell activity, the release/secretion of hormones through exocytosis, and the activity of enzymes. Also important for coagulation of blood and for maintaining the stability of cell membranes and the linkage between cells. On a less acute basis, calcium is important for the structural integrity of bone and teeth.

Answer 476

Calcium homeostasis is tightly controlled; adjustments are made within a range of 5% of normal.

Answer 477

Phosphate is important for the structure of bone and teeth; on a cellular basis, organic phosphate serves as part of the cell membrane and as part of a number of intracellular components.

Answer 478

Phosphate conc are controlled by the same system that control calcium conc. Inorganic phosphate in blood serves as the source of phosphate, which is important for the structure of bone and teeth. Inorganic phosphate also functions as an important hydrogen ion buffering system in blood. Organic phosphate is an important part of the cell, including the plasma membrane and intracellular components, such as nucleic acids, adenosine triphosphate, and adenosine monophosphate.

Answer 479

The most important body pool of calcium involved in homeostasis is the extracellular fluid component. 99% of calcium in the body is in the bone in the form of hydroxyapatite crystals (contain calcium, phosphate, and water). Next largest pool is intracellular calcium. In the inactive cell state, calcium conc are relatively low in the cytosol; calcium is bound to proteins or contained within the mitochondria or granules of the endoplasmic reticulum. Increased intracellular calcium conc are indicative of increased cell activity.

Answer 480

The smallest pool, which resides in the extracellular fluid, is the most important pool of physiologic control of calcium conc in the blood. This component comprises interstitial calcium, blood calcium, and a small (0,5%) but important part of the bone calcium pool; which exists as amorphous crystals or in solution. The soluble bone calcium pool allows access to the large reserve of calcium that resides in bone

Answer 481

The regulation of calcium levels involves control of the movement of calcium between the extracellular fluid and 3 body organs; bone GI tract, and kidneys. The exchange of calcium ions between the extracellular and intracellular fluid occurs in conjunction with the control of intracellular metabolism, with little effect on plasma conc of calcium.

Answer 482

The absorption of calcium from the GI tract is by passive diffusion and active transport. The passive diffusion of calcium across the intestinal mucosa occurs in the presence of high concentrations and, as such, is not an important aspect of calcium absorption. Active transport involves the movement of calcium into the intestinal cell down a conc gradient, which is facilitated by carrier proteins located on the luminal side of the mucosal cell. Calcium is moved through the serosal side of the mucosal cell into the interstitial fluid through a calcium pump system. The active transport adjusts according to the amount of calcium I the diet; becoming more active when calcium conc in the diet are lower, and less active when calcium conc are higher.

Answer 483

Calcium excretion into the GI tract is not affected by calcium uptake, and this can exacerbate conditions involving hypocalcemia. The GI tract serves as the source of calcium for the body, even though both absorption and excretion of calcium occurs through the tract. Vit D plays an important role in the absorption of calcium from the GI tract.

Answer 484

The kidneys serve as the route of excretion of calcium. Most of the calcium that passes into the kidneys is reabsorbed, with a net loss of only about 2 %. This amount is matched by net absorption of calcium by the GI trac.

Answer 485

Most of the filtered calcium in the kidneys is reabsorbed in the proximal tubules; the next largest amount by the distal tubules, and lesser amount by the ascending loop of Henle. The distal tubules are under hormonal control and therefore are the sites of regulation of calcium in the kidneys.

Answer 486

The most important regulation of calcium metabolism between bone and extracellular fluid involves the soluble portion of bone. Amorphous crystals and soluble calcium, which form the source of ready exchange of ions with the blood, are located between the osteoblasts, which line the blood vessel channels, and the osteocytes, which are deeper in the bone. These 2 cell types have cytoplasmic projections that interact intimately through the presence of tight cell junctions.

Answer 487

In order for labile bone calcium to reach the blood, calcium must cross the membrane barrier created by the osteoblasts and osteocytes. Movement of calcium from stable bone into the extracellular fluid occurs, but has little impact on the acute regulation of calcium conc.

Answer 488

The main organ involved in the control of calcium and phosphate metabolism is the parathyroid gland. Most domestic animals have 4 pairs of these glands, located at the 2 lobes of the thyroid gland. The parathyroid cells that are I the active process of hormone secretion are called chief cells, whereas inactive, or degenerate, cells are called oxyphil cells.

Answer 489

Primary parathyroid gland disorders involve excess secretion of PTH (primary hyperparathyroidism (PHPTH) or deficicnecies of PTH secretion (primary hypoparathyroidism). Although both conditions are relative uncommon, PHPTH is diagnosed at a much greater frequency than its counterpart.

Answer 490

The synthesis of PTH hormone is similar to the synthesis of other protein hormones. Prepro-PTH synthesized in the rough ER. Form pro-PTH, and the pro protion is removed by the Golgi apparatus. PTH is secreted by the process of exocytosis. Rapidly metabolized by the liver and the kidneys. Half life of 5-10 min in blood.

Answer 491

Effect of PTH is to increase calcium and decrease phosphate conc in extracellular fluids. PTH has direct effects on bone and kidney metabolism of calcium and indirect effects on GI metabolism of calcium.

Answer 492

The initial effect of PTH on bone is to promote the transfer of calcium across the osteoblast-osteocyte membrane. This level of action occurs without the movement of phosphate and therefore has no effect on phosphate concentrations in blood. PTH has additional effects on stable bone, which results in the resorption of the bone. This effect involves increased osteoclast activity, and an inhibition of osteoblast activity. The effect of PTH on stable bone results in the release of both calcium and phosphate.

Answer 493

PTH acts on the distal convoluted tubules of the kidneys to increase absorption of calcium and decrease renal phosphate reabsorption through an effect in the proximal tubules. PTH is involved also in the activation of vitamin D at the kidney level. PTH mediates the absorption of calcium from the gut indirectly through its effect on vit D.

Answer 494

PTH secretion is controlled by free (ionized) calcium conc in blood; decreases in calcium levels stimulate PTH secretion, and increases in calcium turn off secretion. Both actions are mediate by an effect on cAMP metabolism.

Answer 495

Epinephrine stimulates PTH secretion through stimulation of gb-adrenergic receptors. Magnesium affects PTH secretion in the same manner as calcium, but its physiologic impact is much less. Sleep affects the secretion of PTH; values are highest immediately after waking.

Answer 496

The essential disorder in PHPTH is the excessive synthesis and secretion of PTH by abnormal, autonomously functioning parathyroid “chief” cells. The cause of this hormonal excess is usually a solitary parathyroid adenoma, but an adenoma of more than one gland, adenomatous hyperplasia of one or more parathyroid glands, and parathyroid carcinomas have been identified in both dogs and cats.

Answer 497

By contrast, other forms of hyperparathyroidism (e.g., renal or nutritional secondary hyperparathyroidism) are usually the result of nonendocrine alterations in calcium and phosphorus homeostasis. Such disturbances indirectly affect the parathyroid glands, causing diffuse hyperplasia. However, in these conditions the secretion of PTH is not autonomous. The “hyperplasia” occasionally diagnosed in dogs with PTH is a condition associated with autonomous secretion of PTH. Therefore, histologic description may not indicate primary and autonomous from secondary secretory patterns. Secondary disorders may have calcium conc ranging from low to normal to increased, whereas PHPTH virtually always is associated with hypercalcemia.

Answer 498

Calcium-Parathyroid Hormone feedback system: Serum calcium is the major factor in reulation of PTH secretion. In normal animals, an inverse linear relationship exists between serum calcium and PTH secretions. As calcium conc in the serum decrease, PTH secretion is stimulated to maintain serum calcium conc at some specific level. Like a “calciostat” that operates at a serum calcium conc set point of about 10.5 to 11.5 mg/dl.

Answer 499

OTH secretion increases or decreases regarding the serum calcium conc. In PHPTH, normal negative-feedback homeostatic control is lost and PTH secretion becomes autonomous and chronically increased. This appearance of “autonomous” secretion may be a change in the “set point”. The autonomous secretion of PTH is not suppressible by the increased conc of calcium perfusing the parathyroid gland. Conversely, in secondary hyperparathyroidism, secretion by the parathyroid glands is normally ........................... by increased conc of calcium.

Answer 500

Severe Hypercalcemia. Hypercalcemia develops when the entry of calcium into the extracellular fluid (regardless of the source)overwhelms mechanisms that maintain normocalcemia. Suppressed secretion of PTH is the mechanism to correct hypercalcemia, a process obviously negated when the cause of hypercalcemia is autonomous secretion of PTH or a molecule with similar biologic activity.

Answer 501

In cancer-associated hypercalcemia, the secretion of PTH is suppressed but autonomous synthesis of a humoral factor (parathyroid hormone-related protein (PTHrP), a protein whose structure and biologic activity are quite similar to thate of PTH) by the cancer cells activates osteoclasts, and causes hypercalcemia.

Answer 502

In the setting of accelerated bone resorption, the kidney is the principal defense against hypercalcemia. When renal and endocrine function is normal, any tendency for a rise in serum calcium is attenuated by increase urinary excretion of calcium. This process is inhibited by PTH in PHPTH or by PTHrP in hypercalcemia of malignancy

Answer 503

Because these proteins induce osteoclast-mediated bone resorption, intestinal absorption of calcium, and renal tubular reabsorption of calcium. The ability of the kidneys to excrete the increased filtered load of calcium becomes impaired. Thus, animals with a chronic and persistent excess of PTH lack the first lines of defense against hypercalcemia.

Answer 504

The hypercalcemic state also interferes with renal mechanisms for reabsorption of sodium and water, leading to polyuria. This is due to an acquired inability to respond to antidiuretic (ADH)-in essence, a reverible form of nephrogenic diabetes insipidus.

Answer 505

In PHPTH, hypercalcemia is enhanced by the increased production of vit D and a decrease in the amount of phosphate available to form complexes with serum ionized calcium. This leads to decreased tubular reabsorption of phosphate, hyperphosphaturia, and hypophosphatemia. The result is development of the biochemical triad classic for PHPTH; hypercalcemia, hypophosphatemia, and hyperphosphateuria.

Answer 506

Poor appetite, PU/PD, weakness.

Answer 507

Abnormalities potentially associated with PHPTH (hypercalcemia): urolithiasis or urinary tract infections (i.e., pollakiuria, stranguria, hematuria) and PU/PD, weakness, decreased activity, decreased appetite, weight loss or muscle wasting, vomiting and shivering or trembling. When a hypercalcemic dog has signs or physical examination findings of serious illness, the hypercalcemia is almost always caused by a disease other than PHPTH (e.g. lymphoma, hypoadrenocorticism, renal failure, apocrine gland carcinoma of the anal sac, vitamin D intoxicosis, multiple myeloma).

Answer 508

PHTPH: PD, PU, or both. Secondary incontinence secondary to the PU. These signs are a result of impaired renal tubular response to ADH and impaired renal tubular resorption of sodium and chloride. Together, these alterations account for a significant increase in urine volume and are a direct result of hypercalcemia. This acquired and reversible form of nephrogenic diabetes insipidus causes the production of relatively dilute, solute-free urine. Compensatory PD develops to maintain normovolemia.

Answer 509

Urinary tract calculi or infection: Hypercalcemia causes calciuria, which increases incidence of calculi and infection. Dilute urine also increases incidence of infection.

Answer 510

Listlessness, Lethargy, and Decreased Activity: Increased serum calcium conc depress the excitability of central and peripheral nervous tissue, which may be responsible for these manifestations. Alternatively, these clinical sings may be a reflection of muscle weakness.

Answer 511

Weakness, Exercise Intolerance and Muscle Wasting: Increased serum calcium concentration decrease cell membrane permeability in nervous and muscular tissue. In addition, skeletal muscle weakness, primarily of the proximal muscle groups, may result from a primary neuropathy that ultimately causes muscle atrophy.

Answer 512

Inappetence: Probably a result of both hypercalcemia-induced decreased excitability of GI smooth muscle and direct effects of hypercalcemia on CNS. (renal failure is less common in dogs with PHPTH than in those without)

Answer 513

Shivering, twitching and Seizures: These signs might result from cerebral microthrombi, vasospasm, or other conditions.

Answer 514

Physical examination; parathyroid gland tumors are not palpable in dogs with PHPTH, but cervical masses may be found in afflicted cats.

Answer 515

The diagnostic approach to a dog with confirmed hypercalcemia is to rule out the presence of malignancy and the other differential diagnosis before pursuing the diagnosis of PHPTH: the most common cause of hypercalcemia in dogs is hypercalcemia of malignancy: Lymphosarcoma, apocrine gland carcinoma, multiple myelopma. A variety of neoplasms are encountered less commonly; including mammary gland adenocarcinoma.

Answer 516

Nonneoplastic causes of hypercalcemia; such as renal failure, Addison’s disease, vitamin D toxicosis (risk for acute renal failure) may be suspected after a thorough physical examination.

Answer 517

CBC usually quite normal. Serum hypercalcemia is the hallmark abnormality of PHPTH; the hypercalcemia once diagnosed, remains static or slowly increases over time. Marked lipemia can falsely increase total calcium values determined by some automated analyzers. Hemoconcentration (dehydration) rarely cuases mild hypercalcemia. Hemolysis can falsely increase total serum calcium conc. Young animals normally have mild increases in serum calcium conc. Excess use of oral phosphate binders may cause the serum calcium conc to increase. Acidosis may decrease plasma protein-binding affinity for calcium and increase ionic calcium conc, creating mild physiologic hypercalcemia.

Answer 518

Blood urea nitrogen and serum creatinine are usually within reference limits in dogs with PHPTH (impressive when considering the mean age of the dogs). Dogs with PHPTH may be protected from renal damage, whether this protective effect is due to the low calcium X-phosphate product or some other factor. Renal failure is uncommon (even though both urolithiasis and/or urinary tract infection may increase the risks of renal disease and failure).

Answer 519

Serum inorganic phosphorus (PO4): Low or low-normal serum phosphoru conc are typical of PHPTH. Hypophosphatemia is the result of PTH-induced inhibition of renal tubular phosphorus resorption, resulting in excessive urinary loss.

Answer 520

Hypophosphatemia, when dietary phosphate is adequate and when oral phosphate-binding ages are not being given, is consistent with either PHPTH or hypercalcemia of malignancy. Other causes of hypophosphatemia are less common.

Answer 521

Hyperphosphatemia in the absence of azotemia suggests a nonparathyroid cause for hypercalcemia. When both azotemia and hyperphosphatemia are present, the clinician must rely on the history, physical examination, and other parameters to determine it the primary problem is renal failure with secondary hypercalcemia (uncommon) or hypercalcemia with secondary renal failure (rare). Assay of the serum ionized calcium conc can be of value. Dogs with renal failure and increases in total serum calcium conc usually have ionize calcium conc that are normal or mildly decreased, Dogs with PHPTH have increases in both fractions.

Answer 522

Calcium in plasma or serum exists in 3 forms or fractions; ionized (free calcim), complexed or chelated (bound to phosphate, bicarbonate, sulfate, citrate, and lactate), and protein bound: 34% (free), 10% (complexed) , 56% (protein bound) respectively in healthy dogs.

Answer 523

Total. Ionized= active form. Protein bound calcium; serves as a reservoid or storage pool for the ionized fraction. However, changes in serum conc of albumin and globulin may alter the measured total serum calcium conc without altering ionize calcium levels. Despite an alteration in the total amount of serum calcium resulting from hyperproteinemia or hypoproteinemia, the biologically active ionized calcium conc usually remains within reference limits. Hypoalbuminemia is a common explanation for apparent hypocalcemia (causes no clinical signs, normally).

Answer 524

Hypercalcemia interferes with ADH action and thereby causes a reversible form of nephrogenic diabetes insipidus. Isosthenuria (or hyposthenuria) may develop from any cause of hypercalcemia. Thus the combination of hypercalcemia and dilute urine is considered a “cause-and effect” phenomenon but is not specific. Urine Sediment: hematuria, pyuria, bacteriuria, and crystalluria are identifie frequently on urine sediment examination from dogs with PHPTH.

Answer 525

A prolongation of the P-R interval and a shortening of the Q-T interval due to a shortened S-T segment. Theoretically, decreases in myocardial conduction velocity and shortened refractory periods could predispose the heart to arrhythmias. However, dogs with PHPTH rarely have abnormalities on electrocardiogram.

Answer 526

PTH conc should be or approach being undetectable if a serum calcium conc is high. Serum PTH conc must always be evaluated in the context of the serum calcium conc. Thus, a serum PTH conc within reference limits should not be considered “normal” in any hypercalcemic dog.

Answer 527

Relative to their hypercalcemia (using total or ionized calcium), virtually all dogs and cats with PHPTH have excessive PTH secretion.Serum PTH conc within the reference range should be considered “excessive” in a dog or cat with hypercalcemia, and are consistent with autonomous, abnormal, hormone secretion.

Answer 528

Differential diagnosis for humoral hypercalcemia of malignancy: o Hematologic cancers o Solid tumors with bone metastasis o Solid tumors without bone metastasis Only after testing has failed to identify a malignancy should PHPTH be considered.

Answer 529

General treatment of hypercalcemia Definitive: remove underlying cause Supportive: o Initial considerations: Fluids (0,9% sodium chloride), Furosemide, Sodium bicarbonate, Glucocorticoids o Secondary considerations: Biphosphonates, Calcitonin o Tertiary Considerations: Mithramycin, Ethylenediamine tetraacetic acid, Peritoneal dialysis, hemodialysis. Surgical therapy for primary hyperparathyroidism (Ettinger) New therapies for PHPTH in dogs: -Percutaneous Ultrasound-guided radiofrequency heat ablation. -Percutaneous Ultrasound-Guided Ethanol Ablation.

Answer 530

Primary hyperparathyroidms in cats: In general, the same differential diagnoses for hypercalcemia in dogs apply to cats, excepts that some cats have a diagnosis of “idiopathic hypercalcemia”.

Answer 531

Neoplasia, most commonly lymphoma or squamous cell carcinoma, diagnosed in 30% of the cats. Renal failure diagnosed in 25% of hypercalcemic cats, and half of these had urolithiasis. Only 6% had PHPTH, another 6% had infectious or granulomatous disease (FIP, toxiplasmos, actinomyces, cryptococcosis), and 1 had hypoadrenocorticism. Hypercalcemia is less common in cats than in dogs.

Answer 532

A large percentage of cats have idiopathic hypercalcemia. Some cats have a poor appetite, weight loss, and weakness. Nephrocalcinosis or uroliths may be observed on radiographs or on abdominal ultrasonography in some cats with idiopathic hypercalcemia. It ahs been estimate that up to 33% of cats with calcium oxalate urolithiasis have hypercalcemia. Renal failure may develop.

Answer 533

Hypercalcemia (both serum total and ionized calcium conc). Several cats had cystic calculi and a majority had abnormalities in BUN and serum creatininge conc (such serum biochem abnormalities are not common in dogs with PHPTH). Serum PTH conc in the range within normal to increased. Most of the cats had resolution of PHPTH after surgical removal of abnormal tissue. Several became hypocalcemic and were treated with vit D and calcium. Some cats became hypercalcemic again post op; potentially due to parathyroid adenoma or carcinoma

Answer 534

Hypoparatthyroidism and hypocalcemia Cessation of parathyroid function leads to a decrease in serum calcium and an increase in serum phosphate concentration. Urinary calcium and phosphate excretion diminishes. These changes are due to loss of PTH effects on mobilization of calcium and phosphate from bone, renal retention of calcium and increased absorption of calcium and phosphate from intestine.

Answer 535

Ionized calcium is involved in the release of acetylcholine during neuromuscular transmission. Calcium is essential for muscle contraction and stabilizes nerve cell membranes by decreasing their permeability to sodium.

Answer 536

Calcium’s role as a membrane stabilizer can be best appreciated when it is absent (during hypocalcemia). When the extracellular conc of calcium ion declines to subnormal levels, the nervous system becomes progressively more excitable owing to increased neuronal membrane permeability. Nerve fibers begin to discharge spontaneously initiating impulses to peripheral skeletal muscles, where they elicit concentrations. Concequently, hypocalcemia causes tetany.

Answer 537

Dogs with clinical signs due to untreated hypoparathyroidism usually have serum calcium conc below 6.5 mg/dL.

Answer 538

Mean 4.8 years The clinical course usually begins with an abrupt onset of intermittent neurologic or neuromuscular disturbances that may be initiated or worsened by excitement or exercise. More than 80% of dogs with NOHP and hypocalcemia have had seizures prior to diagnosis. Some had been diagnosed and treated for nonspecific seizure disorders without the benefit of pretreatment laboratory testing. Additional signs included cramping and tonic spasm of leg muscles, focal muscle twitching, generalized tremors, stiff, stilted, hunched, or rigid gait, intermittent lameness. Grand mal convulsions have been observed in 80% of dogs with NOPH; usually last 30 seconds to 3 minutes. Most , but not all, generalized seizures spontaneously cease. Facial rubbing and biting at feet (pain associated with masseter and temporal muscle cramping secondary to hypocalcemia?). Sudden excitement, activity unpredictably may cause sporadic muscle cramping, lameness, pain, irritability, aggressive behavior. Change in personality. Become “mean”. Some signs are vague, but after hypocalcemia is diagnosed, they can all be related to tetany.

Answer 539

Problems caused by hypocalcemia are usually completely reversible with therapy.

Answer 540

Some dogs growle when examined due to pain. Cardiac abnormalities in about 40% of dogs on initial examination. Paroxysmal tachyarrhythmias, muffled heart sounds, and weak pulses.

Answer 541

Much like those clinical signs reported in dogs. Gradual or abrupt onset of signs; like in dogs.

Answer 542

Severe hypcalcemia. Serum phosphorus conc higher than its calcium conc. Normal BUN conc. Absence of absolute hyperphosphatemia in some dogs is likely, in part, due to the broad reference range provided by vet lab. No other abnormal lab findings were common.

Answer 543

Hypocalcemia prolongs the duration of the action potential in cardiac cells. The findings most consistent with hypocalcemia included deep, wide T waves, prolonged Q-T intervals, and bradycardia. No obvious ECG findings could explain the arrhythmias, weak pulses, or muffled heart sounds that were noted on several physical examinations.

Answer 544

Undetectable serum PTH conc in animals that are severely hypocalcemic confirm the diagnosis of primary hypoparathyroidism, assuming that the assay used is reliable and validated. Serum PTH conc may be detectable as “low-normal” in some animals if the assay used is quite sensitive. However, a result in the low reference range would not be “normal” in an otherwise healthy hypocalcemic animal.

Answer 545

Parathyroid-related hypocalcemia Acute Renal failure, Ethylene glycol toxicity Chronic renal failure Hypoalbuminemia Pancreatitis Puerperal tetany (eclampsia). Nutritional secondary hyperparathyroidism Miscellaneous causes of hypocalcemia

Answer 546

Parathyroid-related hypocalcemia: naturally occurring hypoparathyroidism is a rare condition in dogs and cats. Iatrogenic primary hypoparathrypidism has been recognized in dogs and cats after thyroid, parathyroid, or other surgeries of the neck. Magnesium deficiency can cause hypocalcemia.

Answer 547

Acute renal failure, such as occurs with urethral obstruction, ureter obstruction, or ethylene glycol poisoning, can result in abrupt and severe increases in serum phosphate conc. An acute increase in serum phosphate conc can, in turn, cause a reduction in serum calcium conc. This hypocalcemia may be exaggerated in acute renal failure because the rapid progression of these disturbances does not allow for compensatory mechanisms. Cats with ureteral or urethral obstruction and hyperphosphatemia often have associated hypocalcemia, hyperkalemia, azotemia, and sometimes seizures. Ethylene glycol intox can cause severe renal failure, acidosis, and death. The metabolites of this toxin can chelate serum calcium ions and cause tetany.

Answer 548

Chronic renal failure is usually associated with an increase in serum phosphate and normal serum calcium conc. However, either hypocalcemia or hypercalcemia may occur in animals with CKD. Serum ionized calcium conc are often low-normal to low. Reduction in total serum proteins, serum albumin conc or both are encountered in a variety of disorders. Decreased circulating albumin causes a decrease in the protein-bound fraction of circ calcium. However, ionized calcium conc are typically normal.

Answer 549

Hypocalcemia, when it occurs in dogs with acute pancreatitis, is usually mild and subclinical. Coexisting pancreatitis and acidosis increase the ionized fraction of serum calcium and further reduce any chance of tetany.

Answer 550

Puerperal tetany (eclampsia). Acute life-threating condition caused by extreme hypocalcemia in lactating bitches and queens. Often severely hypocalcemic (< 6.5 mg/dL). Most common in small dogs.

Answer 551

Nutritional secondary hyperparathyroidism Dogs and cats fed diets containing low calcium-to-phosphorus ratios, such as beef heart or liver, can develop severe mineral deficiencies. Dietary calcium deficiency results in transient decreases in serum calcium conc, inducing increases in PTH secretion. Reduction in bone-mass follows as calcium is mobilized from bone to replace that lacking in the diet. Additional skeletal problems include bone pain and pathologic fractures. Both are the result of the normal physiologic processes that maintain serum mineral homeostasis. Usually these animals have normal serum conc of both calcium and phosphorus. Occasionally, such an animal is hypocalcemic and rarely this hypocalcemia is severe. These dogs and cats should be treated by providing balanced diets and restricting activity until skeletal remodeling is complete

Answer 552

Commercial phosphate-containing enemas may result in acute, marked hyperphosphatemia and subsequent hypocalcemia after colonic adsorption of the enema solution, especaillly when administered to dehydrated cats with colonic atony and mucosal disruption. Other rare problems include laboratory error, vit D deficiency, use of citrated blood, trauma, medullary carcinoma of the thyroid, primary and metastatic bone tumors, and some forms of chemotherapy.

Answer 553

Emergency therapy for tetany/seizures: diazepam. Hypocalcemia; calcium replacement. ECG monitored infusion; if premature ventricular complexes, or shortening of the Q-T interval is observed, the IV infusion should be briefly discontinued. Fever frequently accompanies tetany due to the intense and persistent muscle activity associated with hypocalcemia. Body temp should be monitored as calciumis adm. Relaxed muscle activity as calcium is given is usually associated with rapid dissipation of fever. Additional measures to lower body temp may result in hypothermia and development of chock. Post-tetany short term maintenance therapy: calcium sc or repeated boluses of calcium iv or calcium in a continuous intravenous solution.

Answer 554

Vit D is the cornerstone of therapy, which acts to increase absorption of calcium present in the intestinal lumen. Oral calcium and Vita D treatment should be started when tetany is being controlled. Vit D in general often needed permanent in dogs and cats with primary naturally occurring parathyroid gland failure. Supplementation calcium in conservative doses ensues that vit D, which raises serum calcium by promoting its intestinal absorption, has a substrate upon which to function. Goal to maintain the serum calcium conc at mildly low to low-normal conc. Such calcium conc are above the level of risk for clinical tetany, and below that which might be associated with hypercalciuria (risk of calculi formation) or severe hypercalcemia and hyperphosphatemia (risk of nephrocalcinosis and renal failure).

Answer 555

It is recommended that dihydrotachysterol or calcitriol be used for long-term treatment; but expensive! Vitamin D2 (Ergocalciferol) can be given as a less-than-ideal but less-expensive alternative. Dihydrotachysterol: the advantage is that this product raises serum calcium con faster than Vit D2 and its effect dissipate faster when adm is discontinued. 1,25-Dihydroxyvitamin D (calcitriol): rapid onset of action and short half-life (of value if hypercalcemia develops). Does not require activation by the kidney

Answer 556

A hormone produced by cells in the thyroid gland which affect calcium metabolism.

Answer 557

?arafollicular or C-cells, are scattered throughout the thyroid gland and are distinctly different from the cells that synthesize thyroid hormones.

Answer 558

Calcitonin acts as a counterbalance to PTH, because it causes hypocalcemia and hypophosphatemia. The effects of calcitonin on mineral metabolism is mainly on bone. Calcitonin decreases the movement of calcium from the labile bone calcium pool (behind the osteoblast-osteocyte barrier) to the extracellular fluid and decreases bone resorption through an inhibitory effect on osteoclasts. Calcitonin also increases movement of phosphate from the extracellular fluid into the bone.

Answer 559

Calcitonin decreases GI activity directly by inhibiting gastric acid secretion and indirectly by inhibiting gastrin secretion. The importance of this in a physiologic sense is not known. Calcitonin also increases renal excretion of calcium and phosphate.

Answer 560

The control of secretion of calcitonin is by calcium: increased calcium conc causes increased secretion of calcitonin.

Answer 561

Hypercalcemia leads to increased conc of calcitonin and concomitant inhibition of PTH secretion. During hypocalcemia, calcitonin synthesisi is inhibited, and PTH becomes responsible for reestablishing normal calcium comc in the extracellular fluids.

Answer 562

GI hormones, including gastrin, cholecystokinin, secretin, and glucagon, stimulate the secretion of calcitonin, gastrin being the most potent. These hormones limit postprandial hypercalcemia.

Answer 563

Vitamin D Important for the absorption of calcium from the gut. It is a steroid-like molecule, and because it is produced in one tissue and transported by the blood to a distant site of action, it should probably be called a hormone instead of a vitamin. All the vit D produced by the body is produced in the skin. Epithelial cells of the skin synthesize the immediate precursor of vit D (7-dehydrocholesterol) from acetate. Exposure of the skin to ultraviolet light results in the formation of vit D (cleavage of C-9 and C10 bonds occurs). The vit D molecule is inactive, and must be transformed by both the liver and kidney before the molecule is biologically activated. The liver first hydroxylates the molecule at the C-25 position, and the kidney subsequently hydroxylates the molecule at C1 to produce the active compound; 1,25 (OH)2-vitamin D (1,25-vitamin D). 1,25-vitamin D is transported by binding to proteins in the plasma, most often to a specific α globulin called transcalcifering (molecule synthesized by the liver).

Answer 564

Important for the absorption of calcium from the gut. It is a steroid-like molecule, and because it is produced in one tissue and transported by the blood to a distant site of action, it should probably be called a hormone instead of a vitamin.

Answer 565

All the vit D produced by the body is produced in the skin. Epithelial cells of the skin synthesize the immediate precursor of vit D (7-dehydrocholesterol) from acetate. Exposure of the skin to ultraviolet light results in the formation of vit D (cleavage of C-9 and C10 bonds occurs). The vit D molecule is inactive, and must be transformed by both the liver and kidney before the molecule is biologically activated. The liver first hydroxylates the molecule at the C-25 position, and the kidney subsequently hydroxylates the molecule at C1 to produce the active compound; 1,25 (OH)2-vitamin D (1,25-vitamin D).

Answer 566

1,25-vitamin D is transported by binding to proteins in the plasma, most often to a specific α globulin called transcalcifering (molecule synthesized by the liver).

Answer 567

Control of the C-1 hydroxylase in the kidney by PTH is the most important control linkage for the synthesis of 1.25 vitamin D. Decreases in calcium conc stimulate PTH secretion, which in turn favors the synthesis of active vit D and increased intestinal absorption of calcium. Phosphate also regulated vit D metabolism. Increased serum phosphate conc stimulate an enzyme that produce an enzyme that promotes hydroxylation of C-24 (instead of C1) by the kidney, which leads to the formation of an inactive vit D molecule. The active molecule 1,25 vit D also regulated itself by decreasing C-1 hydroxylase and increasing C-24 hydroxylase activity; Decreased amounts of active vit D is the result.

Answer 568

Increased absorption of calcium by the GI tract. Vit D stimulates the synthesis of protein (requires several hours) within the mucosal cells, which aids the rate-limiting step in calcium absorption; movement of calcium into the mucosal cell. Vit D also stimulates passive transfer of calcium. Vit D also has effects on bone, promoting the movement of calcium ions from the labile pool into extracellular fluids and the resorption of bone, as well as enhancing the effects of PTH on bone metabolism of calcium.

Answer 569

The control of 1,25 vit D synthesis is by increased PTH and decreased phosphate. Decreased calcium conc results in increased PTH secretion and increased formation of 1,25-vitamin D through enhancement of C-1 hydroxylatin---= increased absorption of calcium by the gut. A decline in phosphate conc results in decreased inhib of C1 hydroxylation, which indirectly results in increased 1,25-vitamin D production and increased absorption of phosphate.

Answer 570

In the overall control of calcium metabolism, PTH is primarily responsible for the maintenance of calcium homeostasis.

Answer 571

The primary target tissue for PTH is the labile pool in bone, changes in renal absorption of calcium are also important. In the case of long-term calcium deficit in the diet; both PTH and 1,25-vitamin D are important for correction of the deficit. Decreased dietary calcium leads to decreased conc of calcium in the extracellular fluids and the release of PTH. PTH affects resorption of calcium by the kidneys, but, of most importance for long-term correction of the problem, it causes increased 1,25-vitamin D secretion with increased absorption of dietary calcium. PTH also contributes to the overall calcium pool through its effect on stable bone (promotes resorptin).

Answer 572

Malignancy, hyperparathyroidism, fungal disease, osteoporosis, hypoadrenocorticism, chronic renal disease, and hypervitaminosis D.

Answer 573

Impaired response of distal renal tubules to ADH.

Answer 574

Depressed excitability of neuromuscular tissue.

Answer 575

Mild GI signs of hypercalcemia include inappetence, vomiting, and constipation. Persistent mild elevations is serum calclum (12-14 mg/dl) can cause uroltihs and signs of urinary tract disease such as hematuria and stranguria. Severe hypercalcemia (>14 mg/dL) can progress rapidly to acute renal failure when the calcium-phosphate product exceeds 60-80 because of mineralization of renal tissue.

Answer 576

An animal with hypercalcemia, azotemia, and hyperphosphatemia could suffer from primary hyperparathyrpidism, primary renal failure with secondary renal hyperparathyroidism, or vit D intoxication.

Answer 577

Hypercalcemia (preferable ionized), hypophosphatemia (unless azotemic), high normal to elevated serum PTH conc, and a mass in the cervical region. A normal PTH conc in the presence of elevated total and/or ionized calcium is considered inappropriate for the calcium level and would be considered diagnostic for primary hyperparathyroidism.

Answer 578

Hypocalcemia (both total and ionized) and hyperphosphatemia.

Answer 579

Iatrogenic (post-thyroidectomy) hypoparathyroidism, chronic and acute renal failure, acute pancreatitis, hypoalbuminemia, puerperal tetany (eclampsia), ethylene glycos intoxication, intestinal malabsorption, and nutritional secondary hyperparathyroidism.

Answer 580

Anorexia, facila rubbing, nervousness, and a stiff, stilted gait. Later signs progress to paresthesias, hyperventilation, and finally, generalized tetany, and/or seizures.

Answer 581

An intact PTH assay, and both ionize calcium and intact PTH chould be assessed

Answer 582

Control of digesting, absorbing, and processing a meal requires intricate coordination of a complex series of events that includes substances provided by the endocrine and nervous systems. The gastrointestinal hormones responsible for controlling digestive function are synthesized within the gastrointestinal tract. Interestingly, these endocrine cells are not present in individual glands but are scattered throughout the stomach and small intestinal epithelium.

Answer 583

Table • 295-1 -- Overview of Important Gastrointestinal Hormones

Answer 584

Endocrine cells (G cells) in the gastric antrum and duodenum secrete gastrin in response to protein meals and, to a lesser extent, gastric distension

Answer 585

Stimulation of gastric acid secretion by gastric parietal cells.

Answer 586

Gastrin acts along with acetylcholine (neurocrine stimulant) and histamine (paracrine stimulant) to determine the final gastric acid secretory output by the parietal cells.

Answer 587

Gastrin receptors are also located on enterochromaffin-like cells in the gut, and stimulation of these cells by gastrin leads to histamine release. Histamine binding to H2 receptors on the parietal cells is necessary for the full acid secretion.

Answer 588

Promotion of gastric mucosal growth, stimulation of gastric pepsinogen secretion, gastric mucosal blood flow, antral motility, pancreatic enzyme secretion, and pancreatic, gastric, and duodenal growth.

Answer 589

The presence of peptides, certain amino acids, calcium, and components in wine, beer, and coffee.

Answer 590

The pH of gastric luminal secretion becomes low (<3).

Answer 591

Pancreatic islet cells (delta cells) are a site of gastrin synthesis and secretion in fetal and neonatal animals. Malignant transformation of these islet cells in adults can result in functional gastrinomas. All but one of the gastrinomas that have been reported to date in the dog or cat have been of pancreatic origin (see Gastrinoma later).

Answer 592

Endocrine cells (I cells) in the duodenum and jejunum secrete CCK in response to intraduodenal fatty acids, amino acids, and H+ ions.

Answer 593

Contraction of the gallbladder and stimulation of pancreatic enzyme secretion. Although CCK receptors have been demonstrated on both gallbladder smooth muscle cells and pancreatic acinar cells, it is now clear that CCK evokes gallbladder contraction and pancreatic enzyme secretion through activation of presynaptic cholinergic neurons at both sites. Other important endocrine actions of CCK include augmentation of pancreatic fluid secretion in the presence of secretin, relaxation of the sphincter of Oddi, inhibition of gastric liquid emptying, and stimulation of pancreatic growth. CCK has two important biologic actions as an enteric or brain neuropeptide.

Answer 594

Secretin-Enteroglucagon-Gastric Inhibitory Polypeptide Family A second structurally homologous gastrointestinal hormone family consists of the gastrointestinal hormones secretin, enteroglucagon, gastric inhibitory polypeptide (GIP), as well as the enteric neuropeptides vasoactive intestinal polypeptide (VIP) and peptide histidine-isoleucine (PHI). All of these substances share considerable sequence homology.

Answer 595

Acidification of the duodenum and jejunum by gastric H+ is the most important stimulus för secretin secretion by endocrine cells (S cells) in the small intestine. Intraduodenal lipid may also stimulate secretin release in some species.

Answer 596

Stimulating secretion of a bicarbonate-rich pancreatic fluid from pancreatic ductal cells. Pancreatic bicarbonate is important in neutralizing gastric acid delivered to the small intestine and in creating an alkaline environment that is close to the pH optimum of pancreatic lipase and co-lipase.

Answer 597

Stimulation of secretion of bile bicarbonate and pancreatic enzymes. The latter effect is observed only in the presence of CCK. Secretin has also been identified in brain neurons, but a functional role for secretin in these neurons has not yet been elucidated.

Answer 598

Endocrine cells (L cells) in the terminal ileum and colon secrete enteroglucagon(s) in response to intraluminal glucose and lipid. Inhibiting gastric acid secretion is the most important gastrointestinal action of the enteroglucagons.

Answer 599

Inhibiting gastric acid secretion is the most important gastrointestinal action of the enteroglucagons. GLP peptides are also involved in the regulation of insulin secretion and glycemic control. GLP-1 is reported to stimulate proinsulin expression and to delay intestinal glucose absorption through inhibition of gastric emptying, thus acting as an incretin hormone during euglycemia to lower blood glucose. GLP-2 is a 33-amino acid peptide hormone released from intestinal endocrine cells following nutrient ingestion. It exerts trophic effects on the small and large bowel epithelium via stimulation of cell proliferation and inhibition of apoptosis. GLP-2 also up-regulates intestinal glucose transporter activity and reduces gastric motility and gastric secretion.

Answer 600

By endocrine cells of the proximal small intestine in response to intraduodenal glucose, fatty acids, and amino acids.

Answer 601

GIP inhibits gastric acid secretion and stimulates intestinal fluid secretion. However, the most important, biologic action of GIP is stimulation of pancreatic insulin release during hyperglycemia.

Answer 602

GIP and GLP-1 function as incretins and are responsible for increased glucose disposal and enhanced insulin responses during intestinal absorption of glucose

Answer 603

Peptide Family A third family of structurally related gastrointestinal hormones is the peptide family, consisting of somatostatin, motilin, and substance P.

Answer 604

Somatostatin, or somatotropin release-inhibiting factor was originally isolated from the hypothalamus and found to inhibit pituitary growth hormone (GH) and thyrotropin release. The same hormone was then found in gut endocrine cells and neurons. It was shown to have endocrine, neurocrine, and paracrine biologic effects.

Answer 605

Endocrine cells (D cells) throughout the gastrointestinal tract secrete somatostatin in response to protein, lipid, and bile.

Answer 606

Inhibits gastric acid and pepsin secretion, pancreatic enzyme and fluid secretion, gallbladder contraction, and intestinal amino acid and glucose absorption. Synthetic forms of somatostatin (Sandostatin, Sandoz Pharmaceuticals) are available for treating gastric acid secretory disorders. Somatostatin also functions as an enteric neuropeptide (e.g., inhibition of intestinal motility) and as a paracrine substance (e.g., inhibition of gastrin secretion).

Answer 607

Motilin is an amino acid peptide found in endocrine cells of the proximal small intestine.

Answer 608

H+ and lipid during the fed state. However, motilin secretion seems to be most important in the interdigestive (fasting) state. During fasting, motilin is episodically released into the serum and initiates phase III of the migrating motility complex. The MMC is a motility pattern that empties the stomach and small intestine of indigestible solids that accumulate during feeding.

Answer 609

Gastric, pancreatic, and biliary secretions with phase III of the MMC

Answer 610

In endocrine cells of the stomach.

Answer 611

It stimulates pituitary GH secretion. “Ghre” is the Proto-Indo-European root for the word “growth,” and the suffix “relin” signifies “releasing substances.” Ghrelin administration also has been shown to stimulate appetite, body growth, and fat deposition. The postprandial gastric expression of ghrelin suggests a gastrointestinal-hypothalamic-pituitary axis that influences GH secretion, body growth, and appetite that is responsive to nutritional and caloric intakes.

Answer 612

Ghrelin and leptin may be the “ying and the yang” of a system that relays peripheral information to the brain and directs the body in the appropriate maintenance of energy reserves and nutritional intake.

Answer 613

5-Hydroxytryptamine (5-HT, or serotonin) is found in endocrine cells (i.e., enterochromaffin cells) and enteric neurons throughout the gastrointestinal tract of most animal species.[1,2,4] In some species, 5-HT is also found in intestinal mucosal mast cells, pancreatic islet cells, and bronchial endocrine cells.

Answer 614

Stimulate gastrointestinal smooth muscle contraction and intestinal electrolyte secretion. Tumors of these enterochromaffin cells (see Intestinal Carcinoids) may be associated with hypermotility and secretory diarrhea due to the effects of 5-HT on motility and secretion.

Answer 615

Glucagonoma: is a rare tumor of the pancreatic alpha cells in dogs and humans, not yet reported in cats. It is characterized by a crusting skin rash, termed necrolytic migratory erythema (NME), and glucose intolerance or overt diabetes mellitus. Excess concentrations of glucagon stimulate hepatic amino acid turnover, gluconeogenesis, and glycogenolysis. In animals it is definitively diagnosed by immunohistochemistry of excised pancreatic tumor tissue. (Laboratory abnormalities included hyperglycemia (five dogs), nonregenerative anemia (three dogs), mild to moderately elevated ALT (four dogs), mild to moderately elevated ALP (three dogs), decreased albumin (two dogs), decreased globulin (one dog), decreased BUN (three dogs), decreased cholesterol (one dog), decreased creatinine (one), and glucosuria (two dogs). Liver function tests normal)

Answer 616

Clinical signs result from elevated plasma gastrin concentrations causing gastric acid hypersecretion. Hypergastrinemia and gastric hyperacidity result in gastrointestinal inflammation and ulceration, maldigestion, and hypertrophy of gastric mucosa. Gastrinomas are uncommon and have been reported in 33 dogs and in 4 cats in the veterinary literature

Answer 617

The most frequent clinical complaints are vomiting and weight loss. Depression, lethargy, anorexia, and intermittent diarrhea are also commonly reported. Less frequent clinical signs include melena, abdominal pain, polydipsia, hematemesis, hematochezia, and obstipation. Physical examination findings are not often remarkable in the early stages of the disease. However, abdominal pain, fever, tachycardia, pale mucous membranes, and dehydration may occur as a result of severe gastrointestinal ulceration or perforation. A palpable abdominal mass was reported in one cat.

Answer 618

Clinical signs result from gastrin-induced gastric acid hypersecretion and gastric mucosal hyperplasia, which may result in gastric ulceration and gastric outflow obstruction. Gastroesophageal acid reflux may cause severe esophagitis and/or ulceration. Diarrhea and steatorrhea are caused by the large amount of acidic fluid entering the duodenum and jejunum and by the high circulating concentrations of gastrin that reduce intestinal water and ion absorption.

Answer 619

LABORATORY FINDINGS The CBC may reveal a regenerative anemia presumably due to gastrointestinal bleeding. Gastrointestinal inflammation may elicit a leukocytosis and neutrophilia with or without a left shift. Biochemical abnormalities: Hypoalbuminemia and hypoproteinemia are due to loss of protein through an ulcerated gastrointestinal mucosa. Persistent vomiting in dogs and cats with gastrinoma may cause hypokalemia, hyponatremia, hypochloremia, and metabolic alkalosis. Diarrhea and reduced food intake could also contribute to the hypokalemia. Hyperkalemia and hypoglycemia have also been infrequently reported and may be due to concurrent hypersecretion of corticotropin or insulin, respectively; in one dog with hyperglycemia, extracts of the islet tumor revealed adrenocorticotropic hormone in addition to gastrin. Increases in serum liver enzyme activities and bilirubin may reflect tumor metastasis to the liver (common) or obstruction of the common bile duct (one dog). (Gastrinomas are generally small in size and are not likely to be visualized consistently with abdominal ultrasonography).

Answer 620

Basal gastric acid secretion and serum gastrin concentration, provocative tests such as secretin (Secretin will stimulate gastrin secretion in patients with gastrinoma, but not in healthy people) and calcium stimulation (calcium infusion stimulates an increase in serum gastrin concentrations in gastrinoma patients), and somatostatin receptor scintigraphy. Demonstration of appropriate histopathologic and immunohistochemical evidence from excised pancreatic tumor or metastatic tissue is necessary to confirm the diagnosis. A definitive diagnosis of gastrinoma would require the findings of hypergastrinemia, histopathologic evidence of pancreatic islet cell neoplasia, and immunohistochemical evidence of gastrin in neoplastic islet cells. At the time of diagnosis, the gastrinoma had metastasized in 85% of cases, usually to the liver.

Answer 621

Treatment of gastrinoma is directed toward surgical resection or reduction of the gastrinoma (challenging because the primary tumors are small and difficult to localize) and/or metastases and medical control of gastrin secretion from the tumor cells. Adjunct medical therapy includes treatment of gastric acid hypersecretion, gastrointestinal ulceration, and fluid and electrolyte losses. Somatostatin (somatostatin analogue, octreotide) inhibits gastrin and hydrogen ion secretion in gastrinomas and in gastric parietal cells.

Answer 622

The most common agents used to control gastric hyperacidity in animals are the H2 receptor antagonists (potent inhibitors of H+ secretion) such as cimetidine (Tagamet), ranitidine (Zantac), famotidine (Pepcid), and nizatidine (Axid). Omeprazole (Prilosec) and pantoprazole (Protonix) are inhibitors of parietal cell H+/K+-ATPase (proton pump inhibitors) and reduce gastric acid secretion with a long duration of action in normal dogs. Sucralfate (Carafate) is an example of a diffusion barrier used to promote ulcer healing. It is a complex of sulfated sucrose and aluminum hydroxide that reacts with gastric acid and binds to necrotic tissue proteins. Misoprostol (Cytotec) is a synthetic prostaglandin that has cytoprotective properties in addition to its direct acid-inhibitory effect. Synthetic prostaglandins may be useful in restoring the protective properties of the gastric mucosal barrier in ulcer patients

Answer 623

Arising from enterochromaffin cells that can be found in the tracheobronchial epithelium, pancreatic ducts, biliary tree, genitourinary tract, stomach, and intestine. 5-HT (serotonin) Carcinoid tumors have been described in 27 dogs and 4 cats. In veterinary medicine, diagnosis is confirmed by histopathologic and ultrastructural examination of the tumors.

Answer 624

Pancreatic Polypeptidoma: PP is commonly found by immunohistochemical staining in human and canine pancreatic endocrine tumors that secrete other enteric hormones such as gastrin, glucagon, or insulin. These patients do not display a characteristic clinical syndrome; however, secretory diarrhea and a macular rash may be associated with excess PP secretion from polypeptidomas.

Answer 625

Pheochromocytoma is an uncommon, functional, often malignant tumor of the adrenal medullary chromaffin cells.

Answer 626

Chromaffin cells in the adrenal medulla are embryologically derived from the neural crest as part of the sympathetic nervous system. The adrenal medulla is essentially a modified sympathetic ganglion composed of chromaffin cells that lack postganglionic processes. Pheochromocytoma is a catecholamine-producing tumor derived from these chromaffin cells. Chromaffin cells are also widely distributed throughout the body, forming paraganglia that usually involute at birth. Tumors arising from the remnant paraganglia in adult animals are referred to as paragangliomas or extraadrenal pheochromocytomas. Sites of metastasis have included liver, lung, regional lymph nodes, spleen, bone, and central nervous system.

Answer 627

The adrenal medulla is essentially part of the sympathetic nervous system. Preganglionic fibers of the sympathetic nervous system are cholinergic and liberate acetylcholine as their neurotransmitter. Postganglionic fibers are adrenergic and liberate norepinephrine and dopamine.

Answer 628

The adrenal medulla is composed of postganglionic neurons (chromaffin cells) without axons. Chromaffin cells produce, store, and secrete a variety of neurotransmitters and neuropeptides.[10] The primary secretory products are catecholamines: norepinephrine and epinephrine, both stored within cytoplasmic vesicles in the chromaffin cells. When the chromaffin cells are stimulated, vesicles are transported to the cell membrane and the contents are expelled via exocytosis

Answer 629

Catecholamines are synthesized from the amino acid tyrosine through a series of enzyme modifications (Figure 296-1). The first step in synthesis involves the conversion of L-tyrosine to L-DOPA through the action of tyrosine hydroxylase. This hydroxylation reaction is the pathways’ rate-limiting step and is subject to negative feedback regulation by norepinephrine.

Answer 630

The normal adrenal gland contains high concentrations of the N-methylating enzyme, which converts norepinephrine to epinephrine. Epinephrine is the predominant catecholamine secreted by the adrenal medulla.

Answer 631

Catecholamine half-life in the circulation is brief (minutes). Two hepatic enzyme systems, catecholamine-O-methyltransferase (COMT) and monoamine oxidase (MAO), mediate the catabolism of catecholamines. Catecholamines and their metabolites are excreted in the urine. Documenting increased urinary concentrations of catecholamines and their metabolites is one method for establishing the diagnosis of pheochromocytoma in human beings.

Answer 632

Tyrosine hydroxylase is the rate-limiting enzyme and is subject to negative feedback control by norepinephrine.

Answer 633

In the normal adrenal medulla, cytoplasmic concentrations of norepinephrine inhibit the activity of tyrosine hydroxylase, thereby controlling catecholamine production. In pheochromocytomas, this negative feedback loop is not present and the metabolism of catecholamines may be markedly increased, further minimizing the feedback inhibition of norepinephrine on tyrosine hydroxylase activity. The mechanisms involved in stimulating catecholamine secretion from pheochromocytoma are poorly understood. Pheochromocytomas are not innervated and catecholamine release is not initiated by neural impulses. Stimulation of catecholamine secretion in response to physiologic stressors such as hypotension, hypoglycemia, hypoxia, and stress is variable and unpredictable.

Answer 634

This response is often exaggerated, causing severe hypertension and life-threatening tachyarrhythmias. Excessive catecholamine secretion also occurs during manipulation of the tumor during surgery. Pharmacologic agents such as metoclopramide and glucocorticoids may also stimulate catecholamine secretion by a pheochromocytoma

Answer 635

Two groups of adrenergic receptors (alpha and beta) are capable of responding to epinephrine. Alpha receptors are divided into a-1 and a-2, and beta receptors are divided into β-1, β-2, and β-3 receptors. The mode of actions of catecholamines is related to their potency at specific receptors (Table 296-2). Tissue response to catecholamines is dependent on the number and type of catecholamine receptors present on the cell membrane. For example, hypertension is a common problem associated with pheochromocytoma which results from vasoconstriction as the smooth muscle surrounding blood vessels contains both α-1 and α-2 receptors. The α-1 receptors predominate when plasma concentrations of catecholamines are increased, resulting in vasoconstriction and hypertension.

Answer 636

Ocular: Mydriasis Cardiovascular: Constriction of arterioles and veins GI: Decreased GI motility, spinchter contration Liver: glycogenolysis Pancreatic acini: Decreased secretion

Answer 637

GI: Decreased GI motility, spinchter contration Liver: glycogenolysis

Answer 638

Cardiovascular: Increase heart rate, contractility, conduction velocity

Answer 639

Cardiovascular: Dilatation of arterioles and Dilatation, relaxation of veins Bronchial smooth muscle: Relaxation GI: Decrease motility Liver: Glycogenolysis Adipose: Lipolysis

Answer 640

Adrenal cortex: Decreased aldosterone secretion Pancreas- beta cells: Decreased insulin PP cells: Increased pancreatic polypeptide

Answer 641

Adrenal cortex: Decreased aldosterone secretion Pancreas: Increased glucagon (alpha cells) Increased somatostatin (D cells) Gastric antrum: Increased gastrin Kidney: Increased renin and erythropoietin Parathyroid: Increased parathyroid hormone Ovary: Increased progesterone Testis: Increased testosterone

Answer 642

Anxiety or nervous behavior, tachycardia, tachyarrhythmias, “pounding” heart, heavy panting, tachypnea, weakness, and findings suggestive of significant hypertension such as retinal hemorrhage or detachment and persistent epistaxis. Physical examination, however, often does not provide clues regarding presence of a pheochromocytoma because a catecholamine surge is usually not happening at the time the dog is examined.

Answer 643

No consistent abnormalities in the CBC, serum biochemical panel, or urinalysis would raise suspicion of pheochromocytoma. Many abnormalities identified in results of routine blood and urine tests are caused by concurrent disorders that are commonly present in dogs with pheochromocytoma. The CBC is usually unremarkable. Leukocytosis can be seen secondary to increased circulating catecholamines or stress. Mild anemia may be present secondary to chronic disease, other concurrent disease, or hemorrhage. Thrombocytopenia or thrombocytosis may indicate acute or chronic bleeding, respectively. Increases in serum liver enzyme activities have been reported in 10% to 25% of dogs with pheochromocytoma. Abnormal serum liver enzyme activities may be secondary to systemic hypertension and changes in hepatic perfusion or may be caused by any number of potential concurrent diseases. Hyperglycemia: Epinephrine has both direct and indirect effects to stimulate hepatic glycogenolysis and hepatic and renal gluconeogenesis, provide muscle with an alternative source of fuel by mobilizing muscle glycogen and stimulating lipolysis, mobilize gluconeogenic precursors, and inhibit glucose utilization by insulin-sensitive tissues like skeletal muscle. Proteinuria, resulting from hypertensive glomerulopathy or concurrent illness, is observed in approximately 20% of dogs with pheochromocytoma. Hypertension should be suspected with sustained systolic pressures >160 mm Hg, sustained diastolic pressures >100 mm Hg, or both.

Answer 644

Measurement of plasma and urinary catecholamines and their metabolites metanephrine and normetanephrine

Answer 645

adrenal tumors most commonly secrete cortisol (i.e., adrenal-dependent hyperadrenocorticism) or catecholamines (i.e., pheochromocytoma) The urine cortisol–to-creatinine ratio and low-dose dexamethasone suppression test are used to rule out hyperadrenocorticism. If hormonal tests for hyperadrenocorticism and serum electrolyte concentrations are normal and clinical signs suggestive of pheochromocytoma are not present, the adrenal mass may still be a pheochromocytoma and treatment with phenoxybenzamine should be considered prior to adrenalectomy.

Answer 646

Phenoxybenzamine noncompetitively blocks the alpha-adrenergic response to circulating epinephrine and norepinephrine. It is considered the drug of choice for preoperative management of hypertension in people with pheochromocytoma.

Answer 647

Phenoxybenzamine is used to reverse vasoconstriction and hypovolemia that is commonly present in humans prior to surgery and to control potentially life-threatening fluctuations of blood pressure and heart rate during anesthesia. Phenoxybenzamine irreversibly binds to alpha receptors. Therefore, the duration of its inhibitory actions persist until additional receptors are produced. For this reason, phenoxybenzamine has a long duration of action and these effects cannot be overridden by tumor-associated surges of catecholamine secretion

Answer 648

Severe hypertension may develop following blockade of beta-receptor-mediated vasodilation in skeletal muscle if prior alpha-adrenergic blockade has not been done.

Answer 649

Phentolamine, a short-acting competitive alpha-adrenergic blocking drug. Blocking of catecholamine receptors, another effect, may be useful to control intraoperative hypertension: Magnesium sulfate might be used. Intraoperative hypotension is managed by decreasing the dose of or discontinuing phentolamine and expanding vascular volume by administering crystalloid fluids, plasma volume expanders, or blood. Dopamine may be indicated in dogs that have a poor response to fluid expansion. Medications that stimulate the release of catecholamines or may precipitate arrhythmias (e.g., metoclopramide, glucocorticoids, ketamine, morphine, halothane) should be avoided

Endocrinology Flashcards

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