Exam I

Question 1

Histology: The pituitary gland sits below the brain in the midline fossa (pocket) of the sphenoid bone. This pocket is known as the _______.

Answer 1

sella turcica

Question 2

Histology: _____ is located anteriorly (rostrally) to the pituitary gland, while the _____ are located inferior to the pituitary. THe relationship between the pituitary and these structures is important as pituitary tumors can impact the visual field

Answer 2

Anterior: Optic chiasm
Inferior: Optic tracts

Question 3

Histology: The cavernous sinus is a reticulated structure that located adjacent to the pituitary gland. It contains multiple vessels and nerves. What structures are found in the medial wall of the cavernous sinus?

Answer 3

Internal carotid and Abducens Nerve (VI)

Question 4

Histology: The cavernous sinus is a reticulated structure that located adjacent to the pituitary gland. It contains multiple vessels and nerves. What structures are found in the lateral wall of the cavernous sinus?

Answer 4

1. Oculomotor nerve (CN 3)
2. Trochlear nerve (CN 4)
3. Trigeminal (CN 5)
   - -ophalmic branch
   - maxillary branch

NOTE: pituitary adenomas can also impact the cavernous sinus

Question 5

Histology: The lobes of the pituitary gland derive from 2 different embryologic origins.

1. The posterior lobe forms from neural ectoderm from the floor of the diencephalon. The neural ectoderm evaginates ventrally from the diencephalon forming the _____
2. The anterior pituitary forms from oral ectoderm in the roof of the mouth. An outpocket forms and grows upward from the roof of the mouth toward the descending neural ectoderm. This outpocket is known as

Answer 5

1. Infundibulum = infundibular stalk and posterior lobe (stalk that connects pituitary to hypothalamus)
2. Rathke’s pouch
   - –loses connection to oral cavity (11th week)
   - –cells in Rathke inc. to form ant. lobe
   - –**persistence = Craniopharyngioma

Question 6

Histology: Rathke’s pouch is formed from oral ectoderm that grows downward from the roof of the ____1____ (primitive oral cavity) . Continued growth dorsally toward the infundibular stalk ultimately leads to the formation of ___2____

Answer 6

1. Stomodeum

2. Anterior pituitary –glandular tissue

Question 7

Histology: ______ is a common tumor in kids/adolescents that arises from embryonic remnants of Rathke’s pouch.

Answer 7

Craniopharyngioma

Question 8

Histology: The pituitary is a compound gland composed of both neural secretory tissue (posterior; neurohypophysis) and glandular tissue (anterior; adenohypophysis).

Answer 8

**See images Anki

Question 9

Histology: Arterial blood supply to the pituitary gland comes primarily from the superior hypophyseal artery and the inferior hypophyseal artery. The superior hypophyseal artery arises from the internal carotid artery and the posterior communicating artery (circle of Willis). What structures does it supply?

Answer 9

Pars tuberalis, Median eminence and infundibulum

NOTE: NO direct arterial supply to the anterior lobe of the pituitary

Question 10

Histology: What are the components of the pituitary gland?

Answer 10

Pars nervosa
Pars distalis
Pars intermedia
Pars tuberalis

Question 11

Histology: Arterial blood supply to the pituitary gland comes primarily from the superior hypophyseal artery and the inferior hypophyseal artery. The inferior hypophyseal artery arises from the internal carotid artery. It supplies what structure?

Answer 11

Pars nervosa

**no direct arterial supply to anterior lobe of pituitary

Question 12

Histology: The _______ of the anterior pituitary forms the primary capillary plexus. This plexus arises from the superior hypophyseal artery in the median eminence and upper infundibulum. It plays a role in picking up secretions from hypothalamic neurons that are destined to regulate cells of the anterior pituitary.

Answer 12

hypothalamohypophyseal portal system

*blood from primary capillary plexus – hypothalmohypohyseal portal veins — pars tuberalis

Question 13

Histology: Blood travels from the primary capillary plexus to the hypothalamohypophyseal portal veins, through the pars tuberalis to a secondary capillary plexus. This secondary capillary plexus is located in the pars ______ and is composed of fenestrated sinusoids.

Answer 13

pars distalis (anterior pituitary)

*doesn’t require transit through systemic circulation

Question 14

Histology: Blood exits the hypophyseal system via hypophyseal veins that drain into the _______ and subseuqently into the systemic circulation to target organs.

Answer 14

Cavernous sinus

Note: evidence for portal system: portal veins from pars distalis, travel to pars nervosa and onto hypothalamus (direct feedback to brain)

Question 15

Histology: The posterior lobe of the pituitary gland is anatomically connected to the hypothalamus. Neural connections between the posterior pituitary and the hypothalamus occurs via the

Answer 15

hypothalamohypophyseal tract

Question 16

Histology: Histology: True/False - The anterior pituitary is functionally, but not anatomically connected to the hypothalamus.

Answer 16

True

Question 17

Histology: The Pars nervosa (posterior pituitary) is NOT an endocrine gland. It acts as the storage site or neurosecretory products formed by neurons of the hypothalamus.

True/False - Axons do NOT terminate on other neurons/cells, but end as Herring bodies located close to fenestrated capillary networks

Answer 17

True

NOTE: Herring bodies are the swollen ends of axon terminals (within the posterior lobe)

Question 18

______ are swollen endings of axon terminals and are the distinguishing feature of theposterior pituitary. Their cell bodies reside in the hypothalamus. They appear sandy/granular.

Answer 18

Herring bodies

Question 19

Histology: Herring bodies contain _____ and _____. Secretion of these hormones is induced by neural impulse.

Answer 19

Oxytocin and ADH

*cell bodies in supraoptic and paraventricular nuclei

1. ADH
   - -prepro-pressophysin to propressophysin
2. Oxytocin
   - -

Question 20

Histology: ____ are astrocyte-like supporting cells found in the posterior pituitary

Answer 20

Pituicytes

Question 21

Histology: ADH functions to inc. water retention by decreasing urine volume and decreasing the rate of sweating.

What are stimui for ADH? What is its MOA?

Answer 21

1. Decrease urine volume
   –stimulus: inc. blood tonicity
   –inc. permeability of CD to water (inserts aquaporins into DCT and CD)
   (concentrate urine) – reabsorb water
2. Decrease sweating
   - -stimulus: dehydration

NOTE: defect = diabedes insipidus

Question 22

Histology: Oxytocin promotes contraction of uterine SM and its synthetic analog promotes the contraction of myoepithelial cells of lactating mammary alveoli.

True/False - Secretion is triggered by neural stimuli that reaches the hypothalamus.

Answer 22

True

Question 23

Histology: The components of the anterior pituitary gland are the pars distalis, pars intermedia and the pars tuberalis.

The pars distalis (main part of anterior pituitary) lacks direct blood supply, while the pars ________, separates the pars distalis and nervosa. Finally, the pars ______ connects the posterior pituitary to the hypothalamus.

Answer 23

1. pars distalis
2. pars intermedia
3. pars tuberalis

Question 24

Histology: The cells of the anterior pituitary are surrounded by the secondary plexus of the hypothalamohypophyseal portal system.

True/False - Hormones from the hypothalamus travel from the primary plexus via the portal system to the secondary plexus, enabling them to reach their target cells bypassing the systemic circulation.

Answer 24

True

Question 25

Histology: The pars distalis is composed of cells that are organized in clumps and cords separated by fenestrated capillaries (2ndary capillary plexus). There are 3 cell types with different staining properties: 1. Acidophils (40%) 2. Basophiles (10%) 3. Chromophobes (50%) List the acidophils

Answer 25

1. Somatotropes 2. Lactotropes all PiGs are pink!!

Question 26

HIstology: ______ are acidophilic cells that produce growth hormone (somatotropin). They are positively regulated by GHRF (from hypothalamus) and by ghrelin (from the GI tract). They are inhibited by somatostatin (hypothalamus).

Answer 26

Somatotropes

Question 27

HIstology: What are pathologies associated with growth hormone?

Answer 27

1. Gigantism - -hormonally active tumors in children 2. Acromegaly - -hormonally active tumors in adults 3. Dewarfism - -decrease in GH secretion in children

Question 28

Histology:________ are acidophils that secrete prolactin which acts in the mammary gland. These cells are acidophilic in the storage stage, but become chromophobic after releasing their contents.

Answer 28

Lactotropes * acidophilic: vesicular storage stage * chromophobic: released contents

Question 29

Histology: Prolactin is regulated (tonically) by ______. Disinhibition occurs via suckling, which leads to the promotion of prolactin release.

Answer 29

Dopamine (inhibits prolactin release) note: PRL acts to inc. dopamine to dec. PRL release

Question 30

Histology: Prolactin is positively regulated by TRH and VIP (vasoactive inhibitory peptide). True/False - Women who have undergone multiple deliveries may undergo hypertophy/hyperplasia of the pituitary glands

Answer 30

True

Question 31

Histology: ______ are basophilic cells that produce TSH. They are stimulated by the release of TRH from the hypothalamus, and inhibited by thyroxin (thryoid gland) and by somatostatin (hypothalamus).

Answer 31

Thyrotropes

Question 32

Histology: _____ are basophils that produce FSH and LH (usually both). They may occasionally produce only FSH or only LH. They are stimulated by GnRH release from the hypothalamus, and are inhibited by PRL.

Answer 32

Gonadotropes

Question 33

Histology: _______ are basophils that produce POMC, the precursor of ACTH. Cleavage of POMC occurs within these cells via proteases.

Answer 33

Corticotropes * stain w/ PAS * stimulus: CRH from hypothalamus * inhibition: cortisol (pituitary and hypothalamus)

Question 34

Histology: _____ are pale staining cells that represent degranulated lactortropes.

Answer 34

chromophobes

Question 35

Histology: ______ is an extension of the anterior lobe. It contains veins of the hypothalamohypohphyseal system. Cells here occur in clusters or cords in association with vessels. These cells include gonadotropes and corticotropes

Answer 35

Pars tuberalis

Question 36

Histology: This layer of the pituitary is composed of 1 layer of cuboidal cells

Answer 36

Pars intermedia

Question 37

Histology: The thyroid gland is located deep to the sternothyroid and sternohyoid muscles. It is located anteriorly in the neck at the level of ______ vertebrae. (anterior to 2nd and 3rd tracheal rings)

Answer 37

C5-T1 * between larynx/trachea medially * R and L lobes (isthmus in between)

Question 38

Histology: The anterosuperior part of the thyroid is supplied by ________ artery, a branch of the external carotid that descends into the gland and then branches into anterior and posterior branches.

Answer 38

Superior thyroid artery * branch of external carotid * anterior and posterior branches

Question 39

Histology: The psoterio-inferior portion of the thyroid gland is supplied by the _______ artery. This artery is a branch of the subclavian artery.

Answer 39

Inferior thyroid artery NOTE: R and L superior and inferior thyroid arteries anastomose within the gland

Question 40

Histology: Venous drainage of the thyroid occurs via 3 veins: 1. Superior thyroid veins 2. Middle thyroid veins 3. Inferior thyroid veins Superior thyroid veins accompany the superior thyroid arteries and drains the ________ pole of the gland. They ultimately drain into the internal jugular vein

Answer 40

superior pole

Question 41

Histology: Venous drainage of the thyroid occurs via 3 veins: 1. Superior thyroid veins 2. Middle thyroid veins 3. Inferior thyroid veins _____ runs parallel to the inferior thyroid artery and drains the middle thyroid into the internal jugular vein

Answer 41

Middle thyroid veins

Question 42

Histology: Venous drainage of the thyroid occurs via 3 veins: 1. Superior thyroid veins 2. Middle thyroid veins 3. Inferior thyroid veins The inferior thyroid drains the inferior pole and subsequently drains into the ________

Answer 42

brachiocephalic vein

Question 43

Histology: Nerves of the thyroid gland are derived from the superior, middle and inferior ______ ganglia. These ganglia have vasomotor functions but lack secretomotor functions

Answer 43

cervical sympathetic ganglia *constrict blood vessels

Question 44

Histology: 1. The thyroid gland develops in the midline between the ____ and ____ pharyngeal arches. 2. Development begins in the 4th week as a sac-like diverticulum on the ventral surface of the pharynx-endoderm. It forms initially at the site of the future ________

Answer 44

1. 1st and 2nd 2. foramen cecum (normal adult remnant of thyroglossal duct) NOTE: forming thyroid eventually fuses with ultimobrachial body (hypobranchial eminence)

Question 45

Histology: As it continues to develop, the thyroid becomes bilobed with a hollow neck, the _____, that connects the lobes. As the embryo and the tongue grows, the thyroid descends into the neck, ventrally toward the developing hyoid bone

Answer 45

neck = thyroglossal duct *connects developing thyroid gland to tongue (atrophies by 6th week(

Question 46

Histology: Continued growth leads to the descent of the thyroid gland into the neck, ventral to the developing hyoid bone. During its descent, the ________ body fuses with the thyroid, providing the parafollicular cells of the thyroid.

Answer 46

ultimopharyngeal body --provides parafollicular cells of thyroid

Question 47

Histology: True/False - The thyroid gland becomes functional at the end of the 3rd month, but produces limited quantity of hormones. Thus, it is still dependent on maternal hormones

Answer 47

True

Question 48

Histology: A patient presents with a cyst along the midline of the neck. You note it moves when he swallows. You suspect

Answer 48

Thyroglossal duct cyst/fistula * persistence of thyroglossal duct (connection b/t thyroid and tongue during thyroid migration) * failure fo form thyroglossal duct altogether = lingual thyroid (thyroid won't migrate)

Question 49

Histology: The thyroid gland is surrounded by a CT capsule. The ________ is a spherical mass of cells that forms the structural unit of the thyroid gland. Follicular epithelial cells are simple cuboidal to columnar cells that surround the inner follicular lumen composed of colloid.

Answer 49

thyroid follicle *follicles are surrounded by capillaries

Question 50

Histology: The follicular epithelium consists of 2 cell types: 1. Follicular 2. Parafollicular What do these cells secrete?

Answer 50

1. Follicular - -T3/T4 2. Parafollicular - -Calcitonin

Question 51

Histology: Colloid contains 1. thyroglobulin 2. enzymes 3. glycoproteins ____ is the backbone upon which thyroid hormone is produced. It occurs on the Y residues of this molecule.

Answer 51

thyroglobulin * precursor to T3/T4 * tyrosine residues

Question 52

Histology: Describe the steps involved in production of thyroid hormone

Answer 52

1. Thyroglobulin is secreted from follicular cells - -exocytosis into follicle lumen 2. Iodide from blood enters cytoplams of follicular cells and diffuses to apical membrane - -released into follicle 3. Iodide --- Iodine (active) via thyroid peroxidase - -as it enters follicle lumen 4. Thyroid peroxidase also catalyzes addition of 1 or 2 atoms of Iodine to Y residues of thyroglobulin - - 1 atom = MIT - - 2 atoms = DIT 5. Oxidative coupling of MIT + DIT = T3 - - DIT + DIT = T4

Question 53

Histology: List the steps associated with secretion of thyroid hormones: 1. ______ from the hypothalamus induces the secretion of TSH (pituitary thyrotropes). TSH binds the TSH receptor on thyroid follicular cells. 2. Thyroid follicular cells undergo receptor-mediated endocytosis of thyroglobulin (with its attached T3 and T4). 3. T3 and T4 are cleaved either via lysosomal pathway or transepithelial pathway

Answer 53

1. TRH -- TSH -- receptor mediated endocytosis --- cleavage of T3/T4

Question 54

Histology: In the ____ pathway, the endocytosed thyroglobulin forms colloidal resorption droplets. These droplets fuse with lysosomes resulting in thyroglobulin degradation and release of T3, T4, MIT and DIT.

Answer 54

lysosomal pathway *cleavage of T3/T4 from thyroglobulin (inc. free T3/T4 = active forms)

Question 55

Histology: In the trans-epithelial pathway, thyroglobulin binds receptor, bypassing the lysosomal compartment, and is transported to the basolateral surface. What is the clinical significance of this pathway?

Answer 55

can result in detectable levels of thyroglobulin in patient's blood

Question 56

Histology: T3 and T4 are released in a T4:T3 ratio of 20:1, with 95% associated with carrier proteins (thyroxin binding protein or nont-specific pre-albumin fraction of serum). Which is more active? Which can be converted?

Answer 56

More active: T3 (5x) Converted: T4 can be converted to T3 in the liver, kidney and heart (via deiodinase) NOTE: T3/T4 provide negative feedback

Question 57

Histology: When inactive, follicular cells appear ______. When active, they appear ______

Answer 57

Inactive: squamous cells Active: columnar

Question 58

Histology: Graves disease is an issue of the ______, while Hashimoto is associated with defective _____

Answer 58

Graves: TSH receptor Hashimoto: thyroid peroxidase

Question 59

Histology: Thyroid hormones are amino acid hormones that act on nuclear receptors, inducing DNA transcription and protein synthesis. Which of the following is an action of thyroid hormones? a. growth b. maturation of CNS c. basal metabolic rate d. inc. metabolism

Answer 59

all of the above * metabolism: inc. glucose absorption, glycogenolysis, gluconeogenesis, lipolysis, protein synthesis and degradation * inc. cardiovascular

Question 60

Histology: True/False - Thyroid hormones (T3/T4) can cross the placental barrier and are essential for normal fetal development. They act to increase GH expression (somatotropes; acidophils,) and when absent can lead to stunted growth

Answer 60

True

Question 61

Histology: Deficiency of thyroid hormones during fetal development can result in irreversible damage to the CNS including: 1. decreased neurons 2. limited neuronal migration 3. defective myelination 4. impaired cognition True/False- Congenital hypothyroidism (CH, cretinism) is included in the OK newborn screening panel to aid in early detection (white matter) and to enable early hormone replacement therapy.

Answer 61

True

Question 62

HIstology: _______ are cells located on the periphery of the follicular epithelium between the follicles. They appear with a basophilic nucleus and a pale staining cytoplasm.

Answer 62

Parafollicular cells --secrete Calcitonin (regulates blood calcium)

Question 63

Histology: Calcitonin is directly regulated by blood calcium levels and is released in cases of hypercalcemia. Calcitonin acts by binding receptors on the surface of _____, enabling the downregulation/inactivation of their activity.

Answer 63

Osteoclasts * calcitonin tones down blood Ca2+ * physiologic antagonist to PTH

Question 64

Principles of Endocrine: Autoimmune disease most commonly underlies disease of hypofunctioning, however notable exceptions do exist. What is an example of this?

Answer 64

``` Graves disease (hyperthyroidism) --thyroid stimulating antibodies ```

Question 65

Principles: Which of the following is an example of dysregulation in primary hormone release by the pituitary? a. Growth hormone tumor b. Prolactinoma c. Graves disease d. Autoimmune thyroiditis

Answer 65

A and B Graves: end organ stimulation (antibodies) Thyroiditis: end organ destruction (hypofunctioning) Anovulation: diminished pituitary hormone release

Question 66

Principles: Hormones involvesd in growth and energy management include 1. Growth hormone 2. Ghrelin 3. Leptin Growth hormone is released from somatotroph cells of the anterior pituitary via normal, pulsatile release. What increases the release of GH? a. Ghrelin b. Insulin c. Sleep d. Alcohol

Answer 66

A- C Increase: - -GHRH - -ghrelin - -insulin (dec. glucose = inc. GH) - -sleep (peak after 1st hour) - -exercise - -fasting (hypoglycemia) - -sex hormones (not DHT)

Question 67

Principles: Growth hormone is released by the anterior pituitary via normal, pulsatile release. What decreases the release of GH? a. free fatty acids b. alcohol c. sleep deprivation d. elevated plasma glucose

Answer 67

B - D Inhibitors: - -FFA's - -DHT - -cortisol

Question 68

Principles: Hormones involved in growth and energy management include 1. Growth hormone 2. Ghrelin 3. Leptin _____ stimulates hunger (orexigenic) and GH release. It is produced by the stomach and is increased in Prader-Willi syndrome.

Answer 68

Ghrelin

Question 69

Principles: Hormones involved in growth and energy management include 1. Growth hormone 2. Ghrelin 3. Leptin _____ is a hormone that increases satiety (decreases appetite). It is released from adipose tissue, and is decreased in cases of starvation

Answer 69

Leptin *LepTIN keeps you ThIN

Question 70

Principles: The adrenal gland is composed of the cortex and the medulla. Three layers constitute the cortex: 1. Zona Glomerulosa 2. Zona Fasciculata 3. Zona Reticularis What are the contents of each of these layers?

Answer 70

1. Glomerulosa - -salt (mineralcorticoids - aldosteron) - -Na/K+ and acid/base regulation - -regulated by Ang II 2. Fasciculata - -sugar (glucocorticoids -cortisol) - -maintains plasma glucose - -BIG FIB 3. Reticularis - -sex (androgens - DHEA) - -secondary source - -peripheral conversion to E2 also

Question 71

Principles: Hormones involved in Fluid and Electrolyte control include: 1. Vasopressin 2. Mineralcorticoids 3. Natriuretic peptides 4. Renin 5. ANS List the sources of these hormones

Answer 71

1. ADH - -posterior pituitary 2. Mineralcorticoids - -aldosterone - -adrenal cortex 3. ANP (atria), BNP (ventricle) 4. Renin - -JG cells of afferent arteriole 5. ANS - -B1 receptors (afferent arteriole) - -detect inc. SYMP tone -- renin release

Question 72

Principles: Glucose control in the plasma and tissues is regulated by multiple factors/pathways: 1. Glycolysis 2. Gluconeogenesis 3. Glycogenesis 4. Glycoegenolysis Glycolysis is glucose degradation to produce 2 ATP and 2 pyruvate. ______ in the liver produces glucose 6-phosphate. In cases of high plasma glucose, insulin is activated which increases glucokinase levels. This in turn signals the liver to work with the glucose that is present in the plasma.

Answer 72

Glucokinase NOTE: Hexokinase is found in other tissues -- sequesters glucose when plasma glucose is low

Question 73

Principles: Glucose control in the plasma and tissues is regulated by multiple factors/pathways: 1. Glycolysis 2. Gluconeogenesis 3. Glycogenesis 4. Glycogenolysis _____ is glucose synthesis. It occurs mostly in the liver, with a small amount occuring in the kidney and intestine. It involves several enzymes including fructose 1,6 bisphophatase and glucose 6 phosphatase

Answer 73

Gluconeogenesis

Question 74

Principles: Glucose control in the plasma and tissues is regulated by multiple factors/pathways: 1. Glycolysis 2. Gluconeogenesis 3. Glycogenesis 4. Glycogenolysis Glycogenesis occurs in the fed state (insulin) and involves glycogen synthase. Glycogenesis is increased in the presence of insulin and glucose-6-phosphate, but decreased in the presence of ______

Answer 74

glucagon and epinephrine * counter-regulatory hormones * fed state = mono-hormonal

Question 75

Principles: Glucose control in the plasma and tissues is regulated by multiple factors/pathways: 1. Glycolysis 2. Gluconeogenesis 3. Glycogenesis 4. Glycogenolysis Glycogenolysis is the breakdown of the stored glycogen and occurs in the fasting state. The initial goal of this process is to maintain plasma glucose levels. It involves the enzyme glycogen phosphorylase. Glycogenolysis is increased by _______ and decreased by ________

Answer 75

- Inc: epinephrine and glucagon | - Dec: insulin, gluc -6-phosphate, AMP, ATP

Question 76

Principles: True/False - Eventually, gluconeogenesis plays a role in the fasting state. It plays a major role in diabetes and often occurs in conjunction with chronic, elevated levels of cortisol and/or growth hormone.

Answer 76

True *primary driver of sustained elevated levels of plasma glucose

Question 77

Principles: Ionized plasma calcium levels are tightly regulated (allowing optimization of muscle contraction and other signal transduction).

Answer 77

True *protein binding, PTH, Vitamin D

Question 78

Principles: List the roles of the Small Intestine, Parathyroid glands, Bone and Kidneys in regulating plasma Ca2+ levels.

Answer 78

1. Small Intestine - -Calcitriol inc. Ca2+ and PO4 absorption 2. Parathyroid - -sense low plasma Ca2+, inc. PTH secretion - -PTH promote PO4 excretion 3. Bone - -PTH stimulates calcium and phosphorus release (osteoclast activation) 4. Kidney - -PTH stimulates calcitriol formation and Ca2+ reabsorption (in DCT) - -inhibits PO4 and HCO3 reabsorption * *phosphate trashing hormone

Question 79

Principles: True/False - a tumor can produce hyperfunctioning of endocrine glands (excess hormone release) OR hypofunctioning due to compression of structure

Answer 79

True * exacerbation: pheochromocytoma * subclinical: insulinoma * some tumors share common mutation/signalling abnormality

Question 80

Principles: True/False - Tumor-associated pathologies (syndromes) are often due to heritable mutations associated with LOF tumor supressor genes (e.g. MEN1) or GOF mutations in proto-oncogenes (e.g. RET involved in MEN2-syndrome).

Answer 80

True **family HX important

Question 81

Principles: True/False - Cushing syndrome is an example of an endocrine syndrome that presents with clinical effects associated with excess cortisol. It may be associated with Carney complex (cardiac myxomas, pigmentations, endocrine hyperactivity).

Answer 81

True NOTE: McCUne-Albright also associated with endocrine hyperfunctioning

Question 82

Principles: True/False - G proteins play a critical role in transduction of signals from specific cell surface receptors (e.g. GHRH, TSH, PTH receptors) to intracellular effectors (e.g. adenylyl cyclase). These second intracellular effectors then generate second messengers (cAMP) that influence cellular responses. True/False - Mutations that induce hyperactivity of G-proteins may seen in a variety of endocrine neoplasms, especially in pituitary, thyroid and parathyroid adenomas.

Answer 82

True *GH adenoma (somatroph adenoma; GNAS mutation -- activation of GSa and inc. cAMP; GOF)

Question 83

Principles: Endocrine and Neuroendocrine tumors often have a ______, monotonic appearance on H and E stains and electron microscopy.

Answer 83

granular *see Path images

Question 84

Principles: 1. Tertiary is at the level of ______ 2. Secondary is at the level of ___ 3. Primary is the level of ______

Answer 84

1. Hypothalamus 2. Pituitary 3. Target tissue/Organ (gland or tissue)

Question 85

Principles: Stimulation tests are often used to evaluate HYPOfunction with the intent to determine the source of the dysfunction. For example: 1. When a hormone is given (e.g. ACTH) resulting in increased cortisol, the dysfunction is associated with ______ 2. When a hormone (e.g. ACTH) is given, with no increase in cortisol, the dysfunction is at the level of

Answer 85

1. Hypothalamus or Pituitary gland | 2. Organ (adrenal gland; Addison)

Question 86

Principles: Which of the following is a cause of endocrine hypofunction? a. autoimmune destruction b. infarction c. decreased stimulation of the gland d. other gland disorders

Answer 86

all of the above * dec. stimulation (pituitary/hypothalamic/lack tropic hormone) * other disorders: enzyme deficiency (congenital adrenal hyperplasia), infection (TB), metastasis, congenital

Question 87

Principles: Suppression tests can be used to evaluate HYPERfunction. Common causes of hyperfunctioning glands includes: 1. Benign adenoma (MC) 2. Acute inflammation 3. Hyperplasia 4. Cancer (paraneoplastic syndrome) True/False - Typically, hyperfunctioning glands often cannot be suppressed because they are autonomous. However, they may be temporarily blocked (e.g. ocreotide for GH adenoma) until surgically removed. There are exceptions to this rule including: prolactinomas and Cushing disease.

Answer 87

True e.g. Ocreotide: block growth hormone Exceptions: 1. Prolactinoma: suppression via DA analog 2. Cushing Disease: suppression via high dose dexamethasone

Question 88

Hypo and Pituitary path: True/False - Typical signaling involves secretion of "releasing hormones" from the hypothalamus that act on the pituitary. These hormones exert effects on the pituitary leading to the release of hormones that travel systemically to their target organs. Finally, the hormones produced by the target tissues exert negative feedback on both the pituitary and the hypothalamus.

Answer 88

True

Question 89

Hypo and Pituitary path: Pathologic disease associated with the hypothalamus and/or pituitary is related to either an excess or deficiency of either "releasing hormones" or pituitary hormones. This leads to local mass effects including: a. Expansion of sella turcica on imaging b. Visual field defects (bitemporal hemianopsia) c. Increased intracranial pressure d. Numbness/Tingling in extremities

Answer 89

A-C

Question 90

Hypo and Pituitary path: Disease involving the hypothalamus can decrease secretion of tropic (releasing) hormones and secondarily decrease secretion of pituitary hormones (secondary hypopituitarism). Examples of this include: a. granulomatous inflammation from Sarcoidosis b. Mycobacterial infection c. Fungal infection d. Radiation to the hypothalamus (Tx of Malignancy)

Answer 90

all of the above *metastatic disease

Question 91

Hypo and Pituitary path: True/False - The anterior pituitary is located in the sella turcica of the shenoid bone. Trauma to this area (fracture at base of skull) that leads to transection of the pituitary stalk may result in dysfunction in both the anterior and posterior pituitary glands (hypopituitarism - mild to severe)

Answer 91

True

Question 92

Hypo and Pituitary path: Hypothalamic disorders include/may lead to 1. Secondary hypopituitarism 2. Central diabetes insipidus 3. Galactorrhea 4. Visual field defects 5. Hydrocephalus 6. Dwarfism in children 7. Precocious puberty in boys _______ is due to lack of synthesis of ADH (or it not getting to the posterior pituitary)

Answer 92

Central diabetes insipidus

Question 93

Hypo and Pituitary path: Hypothalamic disorders include/may lead to 1. Secondary hypopituitarism 2. Central diabetes insipidus 3. Galactorrhea 4. Visual field defects 5. Hydrocephalus 6. Dwarfism in children 7. Precocious puberty in boys ______ is due to the absence of hypothalamic releasing hormones, leading to dec. pituitary activity

Answer 93

Secondary hypopituitarism dec. TRH, CRH, GnRH, GHRH, dopamine

Question 94

Hypo and Pituitary path: Hypothalamic disorders include/may lead to 1. Secondary hypopituitarism 2. Central diabetes insipidus 3. Galactorrhea 4. Visual field defects 5. Hydrocephalus 6. Dwarfism in children 7. Precocious puberty in boys _______ is associated with lack of dopamine resulting increased/unregulated prolactin release.

Answer 94

Galactorrhea

Question 95

Hypo and Pituitary path: Hypothalamic disorders include/may lead to 1. Secondary hypopituitarism 2. Central diabetes insipidus 3. Galactorrhea 4. Visual field defects 5. Hydrocephalus 6. Dwarfism in children 7. Precocious puberty in boys _____ may be caused by hypothalamic lesion with compression of the optic chiasm. It MC causes bitemporal hemianopsia

Answer 95

visual field defects *loss of peripheral in outer temporal halves (outer half of right and left visual fields)

Question 96

Hypo and Pituitary path: Hypothalamic disorders include/may lead to 1. Secondary hypopituitarism 2. Central diabetes insipidus 3. Galactorrhea 4. Visual field defects 5. Hydrocephalus 6. Dwarfism in children 7. Precocious puberty in boys ______ may be caused by a hypothalamic mass that obstructs the ventricles of the brain

Answer 96

hydrocephalus

Question 97

Hypo and Pituitary path: Hypothalamic disorders include/may lead to 1. Secondary hypopituitarism 2. Central diabetes insipidus 3. Galactorrhea 4. Visual field defects 5. Hydrocephalus 6. Dwarfism in children 7. Precocious puberty in boys _____ is due to absence of GHRH, while ___ is due to a midline hamartoma.

Answer 97

1. dwarfism | 2. precocious puberty

Question 98

Hypo and Pituitary path: The hormones released by the anterior pituitary are: My Ant has a FLAT PiG

Answer 98

1. FSH 2. LH 3. ACTH 4. TSH 5. PRL 6. GH

Question 99

Hyperpituitarism is excessive release of hormone from the pituitary. In the case of clinical hyperpituitarism, the tumor is considered functioning (a.k.a. the patient can experience systemic effects of hormone secretion). What is the MC cause of hyperpituitarism?

Answer 99

Adenoma 1. Microadenoma < 1 cm 2. Macoradenoma > 1cm * MC in adults * GNAS1 mutations

Question 100

Hypo and Pituitary path: ____ is the MC hyperfunctioning adenoma. It is suppressible with DA receptor AGONISTS (cabergoline and/or bromocriptine).

Answer 100

Prolactinoma * normal fxn: stimulate lactation * tonic inhibition by DA

Question 101

Hypo and Pituitary path: A patient presents with complaints of loss of libido. She admits to amenorrhea, and infertility. Labs reveal: 1. Serum prolactin levels are > 200ng/mL. 2. Dec. FSH, LH (dec. E2 and progesterone) You suspect

Answer 101

Prolactinoma * PRL inhibits GnRH = dec. LH, FSH * galactorrhea, impotence in males

Question 102

Hypo and Pituitary path: Normal physiologic hyperporlactinemia may occur as a result of pregnancy or suckling. In addition, PRL release may also be stimulated by what hormone?

Answer 102

TRH *hypothyroidism may present with hyperPRL - important to R/O hypothyroidism (via thyroid fxn studies --free T4 and TSH) in px w/ hyperPRL Tx: thyroid hormone replacement

Question 103

Hypo and Pituitary path: Prolactin is tonically inhibited by Dopamine. Early generation DA receptor antagonists can cause hyperprolactinemia by blocking the tuberoinfundibular pathway. What are examples of these drugs? a. chlorpromazine b. prochlorperazine c. hydrochlorithiazide d. lisinopril

Answer 103

A and B 1. typical anti-psychotics - -chlorpromazine (blocks all D receptors) 2. phenothiazine - -prochlorperazine (D2)

Question 104

Hypo and Pituitary path: Growth hormone (GH, somatotropin) is released from the anterior pituitary in response to GHRH, and is inhibited by somatostatin. It has various roles, some of which are direct and others are indirect. What are direct effects of growth hormone? a. stimulate liver synthesis and secretion of IGF-1 (somatomedin C) b. increase lipolysis (dec. fat mass) c. increase muscle and bone growth (inc. lean body mass) d. increase protein synthesis in muscle

Answer 104

A-C Indirect: - -inc. protein synth. in muscle - -inc. muscle/bone growth (pubertal growth) NOTE: IGF-1 = inc. linear/lat. bone growth, cartilage and soft tissue

Question 105

Hypo and Pituitary path: A benign pituitary tumor that secretes excess GH, resulting in gigantism in children and acromegaly in adults. It is the 2nd MC functioning adenoma.

Answer 105

Growth hormone adenoma * gigantism: inc. linear bone growth (unfused epiphyses) * acromegaly: Inc. lateral bone growth (jaw, hands, feet)

Question 106

Hypo and Pituitary path: 1. ________ occurs in the presence of excess GH prior to growth plate closure. It is characterized by markedly accelerated growth + physical manifestations. 2. _______ occurs in the presence of excess GH after growth plate closure.

Answer 106

1. Gigantism (~13-17 y/o) | 2. Acromegaly

Question 107

Hypo and Pituitary path: A 38 year old female presents to the clinic for routine check up. When standing, you note her height is over 7 feet. She complains about increased ring and shoe sizes. You note coarse facial features, with a widened, thickened nose, prominent cheekbones and a bulging forehead (frontal bones). She has thick thickened lips with a prominent jaw and gaps between her teeth. When asked to stick out her tongue, you note enlarged tongue (macroglossia). PMH reveals: - Hypertension - CV disease (including Heart Failure) - Diabetes Mellitus (and glucose intolerance) You suspect?

Answer 107

Somatotroph (GH) adenoma * soft tissue thickening of hands and feet * deepened voice * up to 8 feet tall * prognathism (protruding jaw --mandibular overgrowth)

Question 108

Hypo and Pituitary Path: Somatotroph adenomas are associated with excess GH and subsequent increased in IGF-1 from the liver. This leads to clinical manifestations associated with increased bone growth, cartilage growth and soft tissue growth. Patients often present with gigantism (kids) and/or acromegaly (adults). What are common co-morbidities that accompany this disorder?

Answer 108

1. CV disease (Heart Failure MC cause of death) 2. Diabetes Mellitus (glucose intolerance) - -hyperglycemia (GH is gluconeogenic) 3. HTN - -if uncontrolled -- may lead to HF 4. Inc. colon polyps, colon cancer

Question 109

Hypo and Pituitary Path: Viewing old photos may be useful in identifying GH adenomas, as they may indicate structural changes. What are methods for Dx acromegaly? Treatment?

Answer 109

Dx: 1. Plasma IGF-1 level 2. Oral glucose challenge: - -normally GH dec. w/ inc. glucose; Failure to suppress GH production after oral glucose challenge = adenoma 3. Imaging (MRI) - confirm lesion Treatment: 1. Somatostatin analogs (Pasireotide, Ocreotide) 2. GH receptor blockers (Pegvisomant)

Question 110

Hypo and Pituitary Path: A patient presents with short stature, a small head, saddle nose and prominent forehead. Examination shows small genitalia. Labs reveal: 1. Elevated GH 2. low IGF-1 You suspect

Answer 110

Laron syndrome * defective GH receptors * results in decreased linear growth of bones

Question 111

Hypo and PItuitary: ACTH is released from the anteruir pituitary in response to CRH from the hypothalamus. ACTH stimulates ________ in the adrenal cortex to convert cholesterol to pregnenolone and to stimulate production of glucocorticoids, mineralcorticoids, and adrenal androgens.

Answer 111

cholesterol desmolase

Question 112

Hypo and Pituitary: Excess corticotropin (ACTH) can cause hypercortisolism (Cushing syndrome). Cushing disease is a form of hypercortisolism caused by an ACTH producing pituitary adenoma. How can excess corticotropin be treated?

Answer 112

Surgery or somatostatin activity analog (pasireotide)

Question 113

Hypo and Pituitary: HypOpituitarism is decreased secretion of one or more pituitary hormones. It occurs either as primary hypopituitarism, or secondary hypopituitarism. How do they differ?

Answer 113

1. Primary: - -issue with pituitary gland (at least 75% of gland destroyed) 2. Secondary: - -hypothalamic dysfunction

Question 114

Hypo and Pituitary: Most cases of hypopituitarism result from destruction or loss of anterior pituitary tissue. This may be due to the presence of: 1. Tumors 2. Hemorrhage 3. Necrosis/Vascular 4. Other types of Compression Tumors include non-functioning pituitary adenomas and craniopharyngiomas. Non-functioning pituitary adenomas are MC seen in adults, and present as _______

Answer 114

mass effect = impaired blood flow or destroyed pituitary parenchyma * expanded sella turcica * visual field defects (bitemporal hemianopia) * inc. intra-cranial pressure

Question 115

Hypo and Pituitary: Most cases of hypopituitarism result from destruction or loss of anterior pituitary tissue. This may be due to the presence of: 1. Tumors 2. Hemorrhage 3. Necrosis/Vascular 4. Other types of Compression (empty sella syndrome) _____ is a sudden hemorrhage into a (pre-existing) pituitary adenoma causing severe hypopituitarism. It presents with headache, diplopia (CN III palsy), and possible cardiovascular collapse or death

Answer 115

Pituitary apoplexy - -hemorrhage * *sudden onset headaches, visual disturbances

Question 116

Hypo and Pituitary: Most cases of hypopituitarism result from destruction or loss of anterior pituitary tissue. This may be due to the presence of: 1. Tumors 2. Hemorrhage 3. Necrosis/Vascular 4. Other types of Compression (empty sella syndrome) True/False - Examples of Necrosis associated with hypopituitarism include SHeehan post-partum necrosis, irradiation and other injury

Answer 116

True

Question 117

Hypo and Pituitary: A patient presents with the following complaints: 1. Failure to lactate (PRL; sudden cessation) 2. Failure to resume menses (LH) 3. Loss of axillary/pubic hair (ACTH) 4. Fatigue/lethargy (ACTH) THese are clinical indications of what problem?

Answer 117

Hypopituitarism

Question 118

Hypo and Pituitary: Your patient presents with her newborn for 1 week follow up. She states she had unusually severe hemorrhage during childbirth (due to placenta accreta). She complains since her baby was born she has had sudden cessation of lactation, failure to resume menses, and suffers from extreme fatigue and lethargy. You are concerned she may have

Answer 118

Sheehan syndrome (post-partum necrosis) * hemorrhage -- infarction -- hypopituitarism (hypocortisolism, hypothyroidism, etc.) * may have hemorrhaging before childbirth (placental abruption) NOTE: pituitary normally doubles in size in pregnancy w/out inc. in blood supply

Question 119

Hypo and Pituitary: A patient presents with features of hypopituitarism: 1. failure to lactate (PRL) 2. failure to resume menses (LH) 3. loss of axillary/pubic hair (ACTH) 4. fatigue/lethargy (ACTH) She is diagnosed with primary empty sella syndrome, a disorder cause by an anatomic defect that leads to compression of the pituitary gland. How does primary differ from secondary?

Answer 119

1. Primary - -herniation of arachnoid and CSF into sella turcica -- compressed pituitary * *multiparous hypertensive obese women 2. Secondary --other cause of loss of pituitary tissue (radiation, trauma, surgery)

Question 120

Hypo and Pituitary: The following are other possible causes of hypopituitarism? 1. Hemochromatosis 2. Lymphocytic hypophysitis 3. Sickle cell anemia 4. Hypothalamic destruction _______ leads to Fe deposits in the pituitary, damaging the gland and resulting in deficient gonadotropin

Answer 120

Hemochromatosis

Question 121

Hypo and Pituitary: The following are other possible causes of hypopituitarism? 1. Hemochromatosis 2. Lymphocytic hypophysitis 3. Sickle cell anemia 4. Hypothalamic destruction ____ is an autoimmune disorder that predominantly affects young women during/after pregnancy. It can lead to variable degrees of hormone insufficiency

Answer 121

Lymphocytic hypophysitis

Question 122

Hypo and Pituitary: The following are other possible causes of hypopituitarism? 1. Hemochromatosis 2. Lymphocytic hypophysitis 3. Sickle cell anemia 4. Hypothalamic destruction _____ can cause pituitary infarction, while ______ is most often associated with tumors that cause loss of releasing hormones.

Answer 122

1. SIckle cell anemia - -infarction 2. Hypothalamic - -tumor (benign - craniopharyngioma; malignant) - -loss of releasing hormones

Question 123

Hypo and PItuitary: A 2 year old male presents with vision loss (specifically bitemporal hemianopsia). Imaging reveals a benign tumor in the suprasellar region (suprasellar mass) of the brain. Labs and Histology reveal: 1. tumor derived from remnants of Rathke's pouch 2. Dystrophic Ca2+ 3. Wet keratin "machine oil" in cystic component You suspect

Answer 123

Craniopharyngioma * compress optic chiasm * tumor on midline

Question 124

Hypo and Pituitary: A patient presents with complaints of cold intolerance, weakness and constipation (hypothyroid). Labs reveal decreased T4 and TSH levels, with no increase in TSH after TRH stimulation. What is the most likely cause?

Answer 124

Secondary hypothyroidisim due to TSH deficiency

Question 125

Hypo and Pituitary: A patient presents with complaints of fatigue. She is hypotensive, hypoglycemic and hyponatremic. Labs reveal low plasma ACTH with CRH stimulation (using metyrapone test). You suspect a deficiency in

Answer 125

ACTH -metyrapone: distinguish b/t pituitary issue or adrenal issue - hypoglycemia: cortisol counter regulatory - hyponatremia: dilutional effect due to hypersecretion of ADH (CRH inc. ADH secretion)

Question 126

Hypo and PItuitary: ADH and oxytocin and are produced in the SON and PVN of the hypothalamus, respectively. They are stored in the posterior pituitary. 1. Oxytocin release is stimulated by: _______ to increase contraction of myoepithelial cells lining breast ducts (milk ejection) and _____ to induce uterine contractions. 2. ADH release is stimulated by increased _____.

Answer 126

1. Oxytocin (milk letdown, uterine contraction) - -breast: suckling - -uterine contraction: cervical dilation (stretching) 2. ADH --inc. plasma osmolarity (osmoreceptors in hypothalamus; inc. water reabsorption by kidney) **ADH inhibited by ethanol

Question 127

Hypo and Pituitary: Thirst (inc. osm) stimulates the release of ADH which promotes reabsorption of free water in the CD and DCT of the kidneys. This restores POsm to its normal range, and results in concentrated urine. How does the body compensate in the presence of dec. plasma osmolarity (POsm)?

Answer 127

1. inhibit ADH -- lose free H2O in urine (bring POsm back into normal range -- dilute urine) NOTE: ADH present = concentrate urine; ADH absent = dilute urine

Question 128

Hypo and Pituitary: Diabetes insipidus is associated with ADH. There are two main types: 1. Central 2. Nephrogenic In _____, there is NO ADH presnent. As a result, patients will have dilute urine and excessive urination (polyuria). Plasma will be concentrated (hypernatremia with normal total body sodium).

Answer 128

Central * patient always diluting, never concentrating (even with restricted water) * Posm > Uosm * always thirsty and drinking water (polydipsia)

Question 129

Hypo and Pituitary: Diabetes insipidus is associated with ADH. There are two main types: 1. Central 2. Nephrogenic ______ results from inability of ADH to work on target cells. Patients present similarly to those with Central DI (lacking ability to concentrate urine) and having hypernatremia with normal total body sodium.

Answer 129

Nephrogenic * patient always diluting, never concentrating (even with restricted water) * Posm > Uosm * always thirsty and drinking water

Question 130

Hypo and Pituitary: Which of the following is a potential cause of central diabetes insipidus? a. Trauma b. Familial c. Tumors d. Granulomatous disease

Answer 130

All of the above - trauma: head injury, pituitary/hypo surgery - idiopathic - tumors (pituitary and hypo) - granulomatous (sarcoidosis, TB)

Question 131

Hypo and Pituitary: Nephrogenic diabetes insipidus is often due to a mutation in the ________ gene, leading to lack of ADH sensitive H2O channels in the collecting ducts. It may also be associated with specific drugs including demeclocycline and _______.

Answer 131

1. aquaporin 2 gene 2. lithium 3. hypoercalcemia 4. hypokalemia

Question 132

Hypo and Pituitary: A patient presents with polyuria, polydipsia, dilute urine and normal plasma glucose. You suspect diabetes insipidus. To determine the cause, you perform a water deprivation test. Following water deprivation, you note the patient can successfully concentrate his urine. This leads you to diagnose

Answer 132

Psychogenic "primary" polydipsia * water deprivation = urine osmolarity > plasma osmolarity * if can't concentrate urine (Uosm is still dec.) = Diabetes insipidus

Question 133

Hypo and Pituitary: A patient presents with excessive urination (polyuria), excessive thirst (polydipsia), dilute urine and normal plasma glucose. You suspect diabetes insipidus. To determine the cause, you perform a water deprivation test. Following water deprivation, you note the patient is unsuccessful in concentrating his urine. You determine he has diabetes insipidus. To determine the type, you give desmopressin acetate (DDAVP) a synthetic ADH. This corrects the problem, the patients urine osmolarity goes up (concentrated urine). This is consistent with

Answer 133

Central diabetes insipidus *Treatable with synthetic ADH NOTE: nephrogenic is NOT treatable w/ ADH because the collecting tubules are refractory. Uosm will remain low

Question 134

Hypo and Pituitary: A patient presents to the clinic with mental status changes (hypotonicity of fluids), cellular swelling in the brain, and seizures. Labs reveal: 1. Plasma Na2+ is < 120mEq 2. Inc. Uosm 3. Dec. Posm You suspect

Answer 134

SIADH *inc. ADH = water retention and dilutional hyponatremia Treatment: 1. Restrict water 2. Loop diuretic (lose excess H2O) 2. High solute intake (high salt/protein diet) 4. +/- ADH receptor antagonists (tolovaptan, conivaptan, aquaporin channel water reabsorption)

Question 135

Hypo and Pituitary: What are etiologies of SIADH? a. ectopic production most often seen in small cell carcinoma b. CNS disorders that enhance ADH release c. pulmonary disease including pneumonia and TB d. drugs

Answer 135

all of the above *drugs: halperidol, phenothiazines, TCA's, SSRI's, cyclophosphamide (enhance ADH effects)

Question 136

Pharm: ADH (Vasopressin) antagonists include: 1. Conivaptan (IV) 2. Tolvaptan (oral) These act to block vasopressin action at the ____ receptor. They are most often used for treatment of SIADH and Hyponatremia.

Answer 136

MOA: block V2 receptor

Question 137

Pharm: Adverse effects of ADH antagonists include: a. edema b. confusion c. electrolyte imbalance d. over correction of Na and H2O balance

Answer 137

D only

Question 138

Pharm: ADH (vasopressin) agonists include: 1. Desmopressin acetate (DDAVP) It acts to stimulate _____ and ____ receptors. It is most commonly used to treat Central (non-nephrogenic) diabetes insipidus, Von Willebrand disease, and sleep enuresis

Answer 138

Stimulate V1 and V2 receptors *adverse: edema, confusion, electrolyte imbalance

Question 139

Pharm: ______ is an oxytocin agonist that stimulates oxytocin receptors. It stimulates milk letdown, uterine contractions and controls uterine bleeding.

Answer 139

Oxytocin (PITOCIN) *Adverse: excessive stimulation of SM

Question 140

Pharm: _______ is used to measure increase in TSH (pituitary) and T3/T4 (thyroid) production. It is not as frequently used with the TSH test.

Answer 140

TRH stimulation test *may be use to stimulate prolactin release

Question 141

Pharm: TSH measurement is the gold standard and is the most sensitive and specific test for assessing thyroid function. It measures plasma hormone levels (not dual negative feedback). How is it administered?

Answer 141

Administered: IM or SC Half life: 35 minutes Excretion: Urine

Question 142

Pharm: A TSH measurement demonstrating High TSH and High T3/T4 is indicative of _____

Answer 142

Hyperthyroidiism (level of hypothalamus or pituitary) *MC pituitary

Question 143

Pharm: A TSH measurement demonstrating LowTSH and High T3/T4 is indicative of _____

Answer 143

Hyperthyroidism (Primary dysfuntion - thyroid issue)

Question 144

A TSH measurement demonstrating low TSH and low T3/T4 is indicative of _____

Answer 144

Pituitary dysfunction

Question 145

Pharm: If the TSH test shows High TSH, but low T3/T4 it is indicative of

Answer 145

HypOthyroidism * pituitary is functioning * thyroid is not producing hormone

Question 146

Pharm: TSH (bovine or recombinant) and its analogs are clinically used in diagnostic testing. True/False - Use of the TSH test can aid in diagnosing hypothyroidism and differentiating primary vs. secondary causes. It may also be used in IDing thyroid carcinoma as it enhances uptake of radioactive iodine (131I) by the thyroid gland.

Answer 146

True

Question 147

Pharm: True/False - TSH may also be used as an adjunctive diagnostic tool for serum thyroglobulin (Tg) testing (with or without radioiodine imaging) in the follow-up of patients with well-differentiated thyroid cancer who have undergone thyroidectomy.

Answer 147

True

Question 148

Pharm: ______ is recombinant human TSH. It is a heterodimeric glycoprotein comprised of 2 non-covalently linked subunits (92 and 118 aa's) and 3 glycosylation sites. Its sequence is human pituitary TSH. It binds to epithelial TSH receptors and stimulates iodine uptake as well as synthesis/secretion of Thyroglobulin (Tg), T3 and T4.

Answer 148

Thyrotropin alfa * inc. uptake of radioiodine (scan detection or radioiodine killing of thyroid cells) * Tg = tumor marker NUTSHELL: form of human TSH used w/ radioactive Iodine imaging to test the presence of TG in patients with thyroid cancer (can also remove diseased thyroid tissue).

Question 149

Pharm: True/False - TSH activation leads to the release of Thyroglobulin by thyroid cells. Thyroglobulin functions as a tumor marker that is detected in blood specimens.

Answer 149

True

Question 150

Pharm: Side effects of TSH and analogs are typically transient (<48 hours) and typically present as flu-like symptoms (fever, myalgia, arthralgia, fatigue/malaise, headache and chills in 2-10% of patients. True/False - HSR are possible, resulting in urticaria, rash, pruritis, flushing, and respiratory signs and symptoms

Answer 150

True

Question 151

Pharm: What are contraindications of TSH and analogs?

Answer 151

Coronary artery disease | Adrenal insufficiency

Question 152

Pharm: What are drug interactions of TSH and analogs?

Answer 152

1. sympathomimetics - -additive effect 2. hepatic enzyme inducers - -barbs, rifampin, carbamazepine 3. estrogens - -inc. TBG

Question 153

Pharm: Diagnostic tests of adrenal function use dual negative feedback. These tests include: 1. Corticotropin (CRH) stimulation test 2. Dexamethasone suppression test 3. Metyrapone test _____ uses Corticorelin ovine triflutate to stimulate both ACTH and cortisol production. It is used to differentiate b/t pituitary and ectopic production of ACTH (a.k.a. ACTH-dependent Cushing's).

Answer 153

Corticotropin stimulation test 1. ACTH-dependent - -hypercortisolism = pituitary hypersecretion of ACTH (Cushing) from tumor or non-tumor 2. ACTH-independent - -hypercortisolism = autonomous cortisol secretion by an adrenal tumor

Question 154

Pharm: Diagnostic tests of adrenal function use dual negative feedback. These tests include: 1. Corticotropin (CRH) stimulation test 2. Dexamethasone suppression test 3. Metyrapone test ___Inhibits 11-B hydroxylase (decreased cortisol and increased 11-deoxycortisol). It is used in Dx of secondary adrenal insufficiency.

Answer 154

Metyrapone * not dual neg. feedback * give at midnight w/ snack -- measure plasma cortisol and deoxycortisol in morning

Question 155

Pharm: Diagnostic tests of adrenal function use dual negative feedback. These tests include: 1. Corticotropin (CRH) stimulation test 2. Dexamethasone suppression test 3. Metyrapone test ____ is a long acting glucocorticoid that suppresses cortisol and ACTH production. It is useful in determining source of hypercorticism.

Answer 155

Dexamethasone test

Question 156

Pharm: CRH alone helps determine involvement of ACTH (Is it coming from the pituitary, or is it ectopic/outside source of ACTH?). If you administer CRH in a patient who has high plasma ACTH + high plasma cortisol + ACTHREL and you see: Increased plasma ACTH levels + inc. plasma cortisol levels Most likely Dx is

Answer 156

Cushing Disease (ACTH of pituitary origins) **inc. CRH directly leads to inc. ACTH and cortisol (thus NOT ectopic ACTH)

Question 157

Pharm: CRH alone helps determine involvement of ACTH (Is it coming from the pituitary, or is it ectopic/outside source of ACTH?). If you administer CRH in a patient who has high basal plasma ACTH + high basal plasma cortisol + ACTHREL and you see: Small to no response in ACTH levels (from the pituitary) and small to no change in cortisol levels Most likely Dx is

Answer 157

Ectopic ACTH syndrome *ACTH coming from outside source (tumor secreting ACTH)

Question 158

Pharm: CRH Stimulation test may be used with the Dexamethasone Suppression test (DST). Give 100ug of CRH 2 hours following the last Dex dose in 2 day regiment. If elevated it is _________

Answer 158

Cushing's *if given overnight (2 hours after last dose) and there is a > 50% inc. ACTH and > 80% dec. cortisol = pituitary origin

Question 159

Pharm: There are two different Dexamethasone suppression tests (DST's), the overnight screening test and the standard two day, 2mg test. The overnight screening test is administer as 1mg dexamethasone at 11pm and midnight. Cortisol and ACTH levels are measured in the morning (8am). What is the problem with this test?

Answer 159

High false positive rate * can be followed by 2 day test * *easier to just use the 2 day test

Question 160

Pharm: There are two different Dexamethasone suppression tests (DST's), the overnight screening test and the standard two day, 2mg test. The two day test requires blood to be drawn 2-6 hours after last dose for cortisol measurement. Suppression is expected to appear as: 1. Urine cortisol > 10ug on 2nd day of DEX 2. Serum cortisol < 5ug 3. Plasma ACTH < 5 pg 4. Serum DEX = 2.0-6.5 ng/mL True/False - has greater specificity and higher sensitivity, but requires more patient effort (multiple doses needed) to achieve good Dx results.

Answer 160

True * *should see significant reduction in cortisol and ACTH -- based on response (or lack of) we'll know where problem is * criteria for suppression is lower when measuring serum cortisol

Question 161

Pharm: Administration of metyrapone is expected to cause a decrease in cortisol (<220nm) and an increase in 11-deoxycortisol. What is the expected outcome if the HPA axis is normal?

Answer 161

--inc. CRH and ACTH (compensate for low cortisol levels) **must monitor 11-deoxycortisol = if remain < 7ug/dl then impaired HPA axis

Question 162

Pharm: True/False - Metyrapone testing can aid in verifying the cause of Cushing's. Patients with pituitary dysfunction and or pituitary microadenoma will have inc. ACTH secretion in response to metyrapone. However, patients with ectopic ACTH producing tumors will not. Furthermore, pituitary macroadenomas do not always respond to metyrapone

Answer 162

True

Question 163

Pharm: The cosyntropin stimulation test analyses for ______ adrenal insufficiency (AI). Cosyntropin (ACTH) is administered as an injection. It should trigger the adrenal glands to produce cortisol. It is normal if the plasma cortisol is > 18ug/dL at 30 minutes.

Answer 163

primary adrenal insufficiency (addison's disease) *not to be confused w/ ACTH test which measures ACTH levels in blood NOTE: lack of response will be blunted in cases of recent (2-3 weeks) pituitary surgery

Question 164

Pharm: Growth Hormone Drugs Include: 1. Sermorelin (GHRH) 2. Somatropin (recombinant human GH) 3. Somtrem (recombinant human GH + methionine) 4. Ocreotide (somatostatin analog) 5. Bromocriptine (dopamine agonist) 6. Cabergoline (dopamine agonist) _______ is given IV and is used to stimulate GH release. It has a pulsatile release, and bind specific GHRH cell surface receptors (GPCRs) on somatotrophs.

Answer 164

Sermorelin * expensive * short half life (63 minutes) -- enzymatically degraded in plasma Adverse: --facial flushing, N/V

Question 165

Pharm: Growth Hormone Drugs Include: 1. Sermorelin (GHRH) 2. Somatropin (recombinant human GH) 3. Somtrem (recombinant human GH + methionine) 4. Ocreotide (somatostatin analog) 5. Bromocriptine (dopamine agonist) 6. Cabergoline (dopamine agonist) GH analogs include natural peptide human growth hormone (somatotropin) and synthetic analogs. MOA is via pulsatile release and binding to specific GH cell surface receptors in multiple tissues. What are the direct effects of these drugs? What are the indirect effects?

Answer 165

Direct: stimulates IGF Indirect: anabolic and growth promoting effects (by IGFs)

Question 166

Pharm: GH analogs are administered parentrally (IM or SC). They have a short (20-30 minute) half life w/ IGF peaking at 20 hours. True/False - The effects last longer than the 1/2 life due to slow induction and clearance of IGF's (even though GH clears rapidly, IGF continues to function long after its clearance).

Answer 166

True *metabolized liver/kidney

Question 167

Pharm: Tests for GH deficiency include low baseline IGF-1, IGF-2, and IGF binding protein The insulin tolerance test (ITT) can me used to measure insulin-induced hypoglycemia. Glucose is first reduced to <2.2 mmol/L and then it is measured along with cortisol and GH. What are the expected results when insulin is administered?

Answer 167

Increase in GH 2 hours after insulin administration | > 20mU or 7ug

Question 168

Pharm: Tests for Hypersecretion of GH include: 1. Measurement of IGF-1 or GH 2. Oral glucose tolerance test (OGTT) Measurement of IGF-1 is very accurate for hypersecretion. What is the function of the OGTT?

Answer 168

Also indicative of hypersecretion if = failure to suppress GH levels (to < 4ng) within 2 hours *see table slide 11

Question 169

Pharm: Growth hormone and synthetic analogs may be used as replacement therapy in GH deficiency, Turner Syndrome in girls, and/or AIDS wasting or cachexia. It may also aid in providing GH deficiency diagnosis. When is use of GH/synthetic analogs contraindicated?

Answer 169

Once epiphyses close

Question 170

Pharm: A patient is administered a drug used to treat her hormone deficiency. Following administration, she suffers from the following adverse effects: 1. HA 2. Intracranial hypertension 3. Muscle pain 4. Mild hyperglycemia 5. Antibody production to GH These adverse effects are most likely due to what drug?

Answer 170

GH and analogs *leukemia

Question 171

Pharm: Growth Hormone can have many drug interactions including: 1. Agents that affect its secretion 2. Agents that Inc. GH levels 3. Agents that decreased the response of GH to GHRH Agents that affect its secretion include

Answer 171

1. Insulin - -inc. GH 2. Glucocorticoids - -biphasic -- initial inc. due to inc. GHRH, then GH inhibition (elevated glucose) 3. NSAIDS - -all inhibit

Question 172

Pharm: Growth Hormone can have many drug interactions including: 1. Agents that affect its secretion 2. Agents that Inc. GH levels 3. Agents that decreased the response of GH to GHRH Agents that increase GH levels include _____ and _______. Agents that decrease the response to GHRH include __________.

Answer 172

1. Increase GH - -CLonidine - -Levodopa (inc. GHRH release) 2. Decrease response to GHRH - -Anti-muscarinic drugs

Question 173

Pharm: ________ is a GH antagonist that is used for the treatment of acromegaly (especially if not controlled by surgery and is resistant to somatostatin analogs). It is a pegylated (e.g. polyethylene glycol) analog of GH that blocks GH on target tissue (dec. IGF).

Answer 173

Pegvisomant

Question 174

Pharm: Pegvisomant is a pegylated analog of GH that blocks GH on target tissues (and dec. IGF). What are adverse reactions of pegvisomant? a. rxns at injection site b. swelling of limbs c. chest pain d. hypoglycemia

Answer 174

all of the above * nausea * hepatitis * dec. feedback control by GH regulation -- doubles GH levels

Question 175

Pharm: _______ is a somatostatin analog that inhibits secretion of pituitary and GI hormones including: 1. GH 2. TSH 3. PRL 4. Glucagon/Insulin 5. VIP 6. Gastrin, secretin, motilin, and pancreatic polypeptide This drug may be administered by IV, SC or IM and is more selective for inhibiting GH.

Answer 175

Ocreotide native SRIF: - -1-3 min half life (short) - -not absorbed orally SRIF analog (ocreotide) - -longer half life (80-90 minutes) - -32% excreted unchanged in urine

Question 176

Pharm: Ocreotide may be used to treat which of the following? a. acromegaly b. GH-secreting and Carcinoid syndrome c. VIP secreting tumors d. Insulinoma

Answer 176

all of the above * hyper-functioning endocrine tumors: GH, Carcinoid, VIP * non-FDA approved: Insulinoma, Orthostatic hypotension

Question 177

Pharm: Adverse effects of Ocreotide include a. Insulin suppression b. Gallstone formation c. GI effects (abdominal pain, diarrhea, N/V) d. Hepatotoxicity What are drug interactions?

Answer 177

A-C Interactions: 1. Cyclosporine (dec. bioavailability) 2. B-blockers and Ca2+ blockers (additive)

Question 178

Pharm: PRL is a 198 aa peptide that is well conserved across species with normal levels approximately 5-20ng/mL. There are two major causes of hyperprolactinemia: 1. Tumors 2. Secondary to other organ diseases (other hormones - TRH, VIP, EGF) What are drugs used to treat hyperprolactinemia?

Answer 178

Dopamine (D2) agonists

Question 179

Pharm: Which of the following is a contraindication for the use of D2 agonists? a. Severe ischemic disease b. HTN c. Toxemia pre-eclampsia (abrupt HTN and seizures) d. Pregnancy

Answer 179

A-C

Question 180

True/False - Growth Hormone induces glycolysis (breakdown of glycogen) to increase plasma glucose. It is stimulated by dec. glucose, dec. fatty acids, sleep and exercise

Answer 180

True

Question 181

Pharm: Drugs that increase PRL (and cause drug interactions w/ D2 agonists) include: 1. Phenothiazine (chlropromazine) 2. Butyrophenones (halperidol) 3. MOA inhibitors 4. Antipsychotic drugs and D2 antagonists Anti-hypertensive agents can also interact with D2 agonists causing additive hypotensive effects via _______ receptor blockade.

Answer 181

alpha-1 adrenergic receptor blockade *same as orthostatic hypotension

Question 182

Pharm: Pharmacologic intervention regimen for hyperprolactinemia involves therapy for 12-24 months with periodic prolactin level monitoring. The MC drugs used are: 1. ______ is the primary drug (according to Wallace) 2. ______ was discontinued due to heart valve issues 3. ______ more effective w/ fewer side effects, but MORE expensive

Answer 182

1. Bromocriptine 2. Pergolide 2. Cabergoline *Quinagolide - not in U.S.

Question 183

Pharm: True/False - Drugs used for the treatment of hyperpRL may be tapered when levels are "normal," however, they must NEVER be abruptly discontinued due to increased potential for rebound effects.

Answer 183

True *high recurrence after discontinuation of drug (60% cabergoline; higher with bromocriptine)

Question 184

Pharm: True/False - Recurrence rate of hyperPRL may be related to tumor size when medication is discontinue. For example, bromocriptine tumor shrinkage is a good indicator for surgery. If there is no shrinkage after 1-3 months, surgery may be required

Answer 184

True

Question 185

Thyroid: The steps in thyroid synthesis are as follows: 1. ____ binds leading to transport of inorganic iodide into the follicular cell by the Na-I symporter 2. Iodide is converted to _______ via thyroid peroxidase 3. The _______ residues of the thyroglobulins are iodinated (1 iodine = MIT, 2 iodines = DIT) 4. Coupling of tyrosine residues occurs via ________ 5. Stored in ______ (bound to TG) for up to 3 months 6. TSH release inititates ______ leading to the movement of stored TG into follicular cells 7. Lysozomal enzymes break down TG, freeing T3 and T4 (which diffuse across the membrane into the blood) 8. Majority of T3 and T4 are bound in the blood to _____

Answer 185

1. Thyroglobulin in colloid; Iodide uptake into follicular cells via Na/I 2. Iodide converted to Iodine (thyroid peroxidase) 3. The tyrosine residues of the thyroglobulin are iodinated (1 iodine = MIT; 2 iodines = DIT) 4. Coupling of tyrosine residues (via thyroid perox.) MIT + DIT = T3 DIT + DIT = T4 5. Stored in colloid (bound to TG) for up to 3 months 6. TSH release initates cAMP...movement of stored TG into follicular cells 7. Lysozomal enzymes break down TG, freeing T3 and T4 (diffuse across membrane into blood) 8. Bound in blood to thryoxine-binding globulin (TBG)

Question 186

Thyroid: True/False - There is more T4 product (100%) from thyroid than there is T3 (20%), however, T3 binds the nuclear receptor with greater affinity than T4.

Answer 186

True **T4 can be converted to T3 in target tissue by type I deiodinase (monodeiodination)

Question 187

Thyroid: What is the major source of Iodine?

Answer 187

Diet

Question 188

Thyroid: Embryologically, the thyroid begins in the region of the foramen cecum at the base of the tongue. It descends to the midline location in the anterior neck. Failure to migrate normally can lead to ectopic thyroid (base of tongue MC) or remnants that persist along the migration tract (cysts). It is also possible for the wall of the cyst to contain remnants of thyroid tissue. What are common complications of ectopic thyroid and thyroglossal duct cysts?

Answer 188

1. Infection 2. develop sinus tract to overlying skin 3. develop malignancy within residual thyroid tissue Treatment: cyst excision NOTE: lingual thyroid = MC site of ectopic thyroid tissue (nodular mass that MC appears along midline of the base of the tongue/hyperdense)

Question 189

Thyroid: In the periphery, the unbound, "free" form of hormone is the active form. Thyroid hormones effect the function of essentially every organ system. T3 acts by modifying gene transcription to alter protein synthesis rates and substrate turnover. What are common effects of thyroid hormone?

Answer 189

1. control basal metabolic rate 2. growth/maturation of tissues 3. turnover of hormones and vitamins 4. cell regeneration 5. synthesis of LDL-R's 6. Synthesis of B-adrenergic R's NOTE: Conversion of T4 (via deiodination) to T3 allows for tight control and protein binding.

Question 190

Thyroid: Hyposecretion of thyroid hormone may be due to a. agenesis b. atrophy c. destruction d. tumors

Answer 190

A-C *tumors and hyperplasia = hyperfunctioning

Question 191

Thyroid: There are different lab tests that may be used to analyze thyroid function, TSH being the most important analyte to measure. With thyroid testing, Total T4 measures both bound (T4-TBG) and free T4. Normally, only 1/3 of TBG sites are occupied by hormone. However, increased TBG protein is expected to lead to compensatory inc. in Free T4 by the thyroid to maintain normal levels. What are causes of increased TBG? Decreased TBG?

Answer 191

1. Increased TBG - -Estrogen 2. Dec. TBG - -androgens - -nephrotic syndrome NOTE: Inc. TBG = more hormone bound = dec. free hormone. Thus, compensatory Inc. T4 to normal level (NET = Inc. Total T4 (inc. bound); but free T4 is normal - normal TSH) *similar to transcortin (cortisol binding protein) and cortisol

Question 192

Thyroid: _______ is the single most important test for thyroid hormone. It is increased in the presence of primary hypOthyroidism (MC), and decreased in secondary and tertiary hypOthyroidism and hypErthyroidism.

Answer 192

Plasma TSH * Plasma T3/T4 (free/total) - -inc. - hypEr (more hormone produced) - -dec. hypO (less hormone produced)

Question 193

Thyroid: _______ uses Iodine 131 or Technetium 99 to measures synthetic activity of the thyroid (i.e. thyroid function). It also assesses the thyroid anatomically. Uptake of Iodine indicates increased T4 synthesis (i.e. Graves disease), while decreased uptake indicates the thyroid gland is inactive.

Answer 193

Radioactive Iodine uptake (RAIU) - inc. uptake = inc. T4 - dec. uptake = inactive - impaired uptake = thyroiditis - excess exogenous hormone = supressed TSH/atrophy

Question 194

Thyroid: Thyroid scans (Scintography) assess the anatomic picture of the thyroid gland. Report of the presence of a cold nodule indicates ______, while a hot nodule indicates ______

Answer 194

cold nodule -- dec. or no uptake or labeled radioisotope (cyst, adenoma, cancer) hot nodule - inc. uptake (toxic nodular goiter)

Question 195

Thyroid: _______ describes a condition caused by a structural or functional derangement that interferes with the production of thyroid hormone. It is MC in women than in men, with increased prevalence with increasing age. It can result from a defect anywhere in the HPA-thyroid axis.

Answer 195

Hypothyroidism * MC cause = autoimmunity * Other: post-surgical or post-ablative state (2nd MC) * Iodine deficiency = MC in developing world * Drugs = Lithium, Iodides, p-aminosalicylic acid

Question 196

Thyroid: A 45 year old female presents with painless enlargement of the thyroid. She develops increasing lethargy and weakness over the last 3 years. She admits to progressive weight gain and complains of consistent cold, even in hot weather. She exhibits alopecia, along with coarse, dry skin. Her skin has a yellow tint and her face (periorbital), hands and feet are puffy with dough like skin. Labs reveal: 1. anti-thyroglobulin and anti-thyroid peroxidase antibodies. 2. Increased TSH, decreased T4 Histology reveals chronic inflammation of the thyroid with germinal centers. Presence of Hurthle cells (pink, oncocytic cells,) and fibrosis. You suspect

Answer 196

Chronic autoimmune thyroiditis (Hashimoto) * MC middle age females * gradual signs hypOthyroidism Symptoms: - weight gain, carpal tunnel syndrome (median), mental slowness, yellowish skin, periorbital puffiness, constipation, depression, diastolic HTN - dec. metabolic rate, SNS (dec. B-adrenergic tone)

Question 197

Thyroid: True/False - Patients with Hashimoto thyroiditis, hypothyroidism may be preceded by transient, initial stage of hyperthyroidism (thyrotoxicosis; Hashitoxicosis) due to release of thyroid hormones (T3/T4) from damaged thyroid cells.

Answer 197

True *inc. risk other autoimmune diseases and lymphoma

Question 198

Thyroid: What is the mechanism associated with Hashimoto thyroiditis?

Answer 198

*due to autoimmune destruction of thyroid cells by cytotoxic T cells (breakdown in self tolerance to thyroid autoantigens)

Question 199

Thyroid: Patients with Hashimoto thyroiditis tend to have what co-morbidities?

Answer 199

1. dilated cardiomyopathy 2. bradycardia (dec. B-receptor synthesis) 3. Hypercholesterolemia (dec. LDL receptor synthesis) 4. Periorbital myxedema 5. Yellow discoloration - -dec. conversion of B-carotenes into retinoic acid

Question 200

Thyroid: Hashimoto thyroiditis (chronic lymphocytic thyroiditis) occurs as a result of CD 8+ cytotoxic cell destruction of thyroid follicular cells, as well as cytokine-mediated cell death via CD4 signalling. CD 4 T-cells produce inflammatory cytokines such as _______ in the thyroid gland, followed by subsequent activation and recruitment of macrophages. This leads to damage to follicles and shrinking of the thyroid gland (resembles lymph node in surgery).

Answer 200

IFN-Y * key antibodies: anti-thyroglobulin, anti-thyroid peroxidase (TPO; microsomal) * associated with HLA-DR5 * may have blocking antibodies: against TSH

Question 201

Thyroid: How is Hashimoto treated?

Answer 201

Thyroid hormone replacement

Question 202

Thyroid: A 47 year old female presents with fever and complaints of thyroid pain/tenderness. She states she began to have jaw pain following an upper respiratory infection. Labs reveal: 1. Increased ESR or CRP 2. Inc. T3/T4 3. Dec. TSH 4. Dec. or hazy on radiologic scan Histology reveals: 1. Multi-nucleated macrophages and lymphocytes getting together (granuloma) You suspect

Answer 202

Granulomatous thyroiditis (DeQuervain/subacute thyroiditis) * self-limited *(1-2mos) * hyperthyroid euthyroid hypothyroid recovery (euthyroid) NUTSHELL: follows viral (URI) and presents with initial hyperthyroidism followed by hypothyroidism

Question 203

Thyroid: A 27 year old female with Lupus presents to the clinic for follow up after delivering her 2nd child. She presents with transient hypo or hyperthyroiditic symptoms, but denies any pain. What do you suspect? How do you treat?

Answer 203

Postpartum thyroiditis * self limiting * painless "autoimmune" * resemble lymphocytic thyroiditis histologically * post-partum women * MC women w/ other autoimmune disorders

Question 204

Thyroid: A patient presents to the clinic with complaints of difficulty swallowing (dysphagia). She admits to dyspnea. You note hoarseness and abnormal, high pitched musical breath sounds during inhalation (stridor). Physical examination reveals extensive, (painless) fibrosis of the thyroid gland and surrounding tissue. The thyroid tissue is rock hard on palpation, and clinically resembles anaplastic thyroid carcinoma. You suspect a. Riedel thyroiditis b. Toxic nodular thyroid c. Squamous cell adenocardinoma

Answer 204

Riedel thyroidtitis * chronic inflammatory infiltrate * morbidity - compressive symptoms (dysphagia, dyspnea) * may be associated with hypothyroidism * manifestation of IgG 4- related systemic disease

Question 205

Thyroid: An infant presents with his mother for well check. Physical exam reveals dysmorphic facial features with protruding tongue and a puffy face. The infant has shortened extremities, and short stature. Umbilical hernia is present along with pot-belly appearance. Severe intellectual disability is present. You suspect _______

Answer 205

Congenital hypothyroidism (cretinism) *rare due to - Dietary Iodine supplementation

Question 206

Thyroid: ______ implies excessive thyroid hormone release directly from the thyroid gland. This leads to clinical symptoms.

Answer 206

Hyperthyroidism

Question 207

Thyroid: _____ is the clinical manifestation of excess thyroid hormone at the tissue level due to inappropriately high circulating thyroid hormone concentrations

Answer 207

Thyrotoxicosis *hyperthyroidism: Subset of thyrotoxicosis (excess thyroid hormone synthesis by the thyroid gland)

Question 208

Thyroid: What are the MC causes of Hyperthyroidism? a. diffuse hyperplasia of thyroid b. hyperfunctional multinodal goiter c. hyperfunctional thyroid adenoma d. hyperfunctional prolactinoma

Answer 208

A - C --diffuse hyperplasia: Graves disease (MC)

Question 209

Thyroid: A patient presents with complaints of weight loss and heat intolerance. She admits to difficulty sleeping (insomnia), anxiety and restlessness. She states her husband complains she is irritable and gets frustrated because she tends to lost her ability to concentrate. She admits to increased stooling (hyperdefecation). Past medical history reveals: 1. HTN 2. Tachycardia and atrial fibrillation (inc. B-receptors) 3. Hyperglycemia and Hypercalcemia 4. Inc. LDL and B receptor synthesis Physical Exam Reveals brisk, deep tendon reflexes.

Answer 209

Hyperthyroidism * *inc. basal metabolic rate * *SNS effects

Question 210

Thyroid: ______ is an autoimmune disorder characterized by the production of auto-antibodies against multiple thyroid proteins. It is MC in women. It is associated with TSI (thyroid stimulating immunoglobulins; IgGs) antibodies against the TSH receptor. These antibodies bind to and stimulate TSH causing type II hypersensitivity reaction.

Answer 210

Graves disease *associated w/ HLA-DR3 and B8

Question 211

Thyroid: A patient presents with complaints of weight loss and heat intolerance. She admits to difficulty sleeping (insomnia) and states that her husband has complained about her recent irritability and anxiety. On PE you note a staring gaze, lid lag, and expthalmos. On her neck is symmetrical, non-tender thyromegaly (diffuse hyperplasia of the thyroid gland). Pretibial myxedema is present (later finding). You suspect the most likely cause is

Answer 211

autoantibodies against TSH (TSI immunoglobulins) * *This is Graves disease * *inc. B-adrenergic tone; inc. SNS and hypermetabolism

Question 212

Thyroid: True/False - Patients with Graves disease often have co-morbidities including HTN, tachycardia and atrial fibrillation. They tend to also present with hyperglycemia.

Answer 212

True

Question 213

Thyroid: The classical triad of Graves disease is 1. Goiter 2. Opthalmalopathy 3. Pretibial myxedema (later finding) True/False - The eyes are the most striking feature of Graves disease, presenting with wide, staring gaze and lid lag. Ocular muscles tend to have atrophy with fatty infiltration and focal interstitial lymphocytic infiltrates. Furthermore, the eyes show accumulation of loose CT behind the orbit.

Answer 213

True 1. wide, staring gaze, lid lag/stare - -SNS overstimulation (superior tarsal) - -functions w/ levator palpebrae superioris muscle to raise upper eyelid 2. Ocular atrophy 3. Loose CT behind orbit - -true thyroid opthalmopathy w/ proptosis only in graves disease 4. Retraction of upper eyelids

Question 214

Thyroid: The classical triad of Graves disease is 1. Goiter 2. Opthalmalopathy (exopthalmos) 3. Pretibial myxedema (later finding) ____ is uncommon. It is related to increased mucin in the dermis, and presents as stringy, hyaluronic acid (myxedema fluid). The pathogenesis is unknown. This, in combination with exophtalmos is unique to Graves disease.

Answer 214

Pre-tibial myxedema * Inc. hyaluronic acid deposition in the dermis and deeper tissues * non-pitting edema

Question 215

Thyroid: True/False - Other noticeable dermal effects in patients with Graves disease include soft, warm, flushed skin which serves to increase heat loss, and increased sweating (leading to inc. calorigenesis). Patients may also present with acropachy or clubbing of the fingers. This is thought to be due to osteoclast stimulation by ______

Answer 215

Thyroxine * acropachy: soft tissue swelling of the hands and clubbing of the fingers * MC metacarpal bones

Question 216

Thyroid: True/False - Both opthalmalopathy and pretibial myxedema may persist after treatment.

Answer 216

True

Question 217

Thyroid: True/False - Pre-tibial myxedema and exopthalmos are unique to Graves disease. These clinical presentations are due to the presence of T cell lymphocytic infiltrate and depositions of GAGs (by fibroblasts). This leads to edema in the tissue.

Answer 217

True * *fibroblast proliferation, inflammation and accumulation of GAGs (especially hyaluronic acid) * *T cell -- cytokines -- fibroblasts (TNF-a; IFN gamma)

Question 218

Thyroid: Patients with Graves disease may present with heart defects including: a. elevated cardiac contractility and output b. tachycardia, palpitations and cardiomegaly c. arrhythmias d. heart failure

Answer 218

all of the above * *inc. CO (hypermetabolic state) * *arrhythmias (a-fib in older px) * *heart failure (if pre-existing cardiac disease)

Question 219

Thyroid: True/False - Myocardial changes may occur in patients with Graves. This is due to lymphocytic and eosinophilic infiltrates, mild fibrosis, myofibril fatty change and increased size and number of mitochondria.

Answer 219

True

Question 220

Thyroid: Thyroid: A patient presents with complaints of weight loss and heat intolerance. She admits to difficulty sleeping (insomnia) and states that her husband has complained about her recent irritability and anxiety. On PE you note a staring gaze, lid lag, and expthalmos. On her neck is symmetrical, non-tender thyromegaly (diffuse hyperplasia of the thyroid gland). Pretibial myxedema is present (later finding). You suspect Graves. How is this Dx?

Answer 220

* Lab and Ancillary 1. Inc. T4, dec. TSH 2. Radioactive Iodine uptake - -diffuse inc. in gland = Graves - -inc. uptake in soltary nodule = toxic adenoma Histology: --scalloping (enlarged follicles)

Question 221

Thyroid: Toxic multinodular goiter induced hyperthyroidism is hyperthyroidism induced by a _________ mutation. It is characterized by the presence of focal patches of hyperfunctioning follicular cells, independent of TSH. Radiology/Nuclear medicine (RAIU) may be used to distinguish this disorder from Graves disease

Answer 221

TSH receptor mutation * "hot" nodules on radionucleotide scan * "plummer syndrome" = hyperthyroid develps late in course

Question 222

Thyroid: _____ MC presents in patients with either: 1. abnormal thyroid functioning (e.g. Graves or autonomously functioning nodule) 2. abnormal iodine metabolism/stores It is MC reported in patients with endemic goiters who move from an area with Iodine deficiency, to areas with iodine abundance.

Answer 222

Iodine induced hyperthyroidism * Jod-Basedow phenomenon * Inc. dietary iodine does not cause clinical effects in normal, healthy patients * Seen in Graves, Toxic multinodular, and w/ amiodarone

Question 223

Thyroid: ______ occurs with excessive iodine intake that leads to temporary inhibition of thyroid peroxidase. This results in decreased organification (dec. T3/T4). It may occur in both normal and in patients with thyroid disease. It differs from Jod Basedow in that it can be seen in normal patients, and usually requires large quantities of excess iodine to be consumed (whereas JB requires small).

Answer 223

Wolff-Chaikoff effect

Question 224

Thyroid: A 24 year old female with a past medical history of Graves, currently being treated presents with intractable N/V and diarrhea. She also complains of dysuria. She exhibits fever (hyperpyrexia), tachycardia, HTN and neurologic and GI abnormalities. Tachycardia is out of proportion to the fever. Labs: *Excessive TH release You suspect thyroid storm based on your patient's history of improperly treated hyperthyroidism/thyrotoxicosis. Her Thyroid is bilaterally enlarged with a bruit. What is the prognosis?

Answer 224

*Acute, life threatening hypermetabolic state that is Fatal if untreated * Rapid Dx and aggressive Tx critical * Death from dysrhythmias * high output heart failure Tx: --corticosteroids, thryoid suppressive therapy, SNS blockade

Question 225

Thyroid: The following are signs and symptoms of _______: 1. weight gain 2. dry skin 3. constipation 4. cold intolerance 5. puffy skin 6. hair loss 7. fatigue 8. Menstrual irregularity

Answer 225

Hypothyroidism

Question 226

Thyroid: The following are signs/symptoms of ____: 1. Tachycardia 2. Anxiety, irritability 3. Inc. sweating 4. Difficulty sleeping/insomnia 5. Tremors in the hands 6. Weakness 7. Diarrhea 8. bulging eyes, puffiness, dryness 9. Pre-tibial myxedema

Answer 226

HypErthyroidism

Question 227

Thyroid: TSH along when combined with clinical presentation can help distinguish between hyperthyroid and hypothyroid. What would you expect in terms of Serum T4 levels, Free T4 (FT4), Serum TSH, and I uptake in the following: 1. Graves 2. Excess hormone/initital thyroiditis 3. Primary hypothyroidism 4. Secondary hypothyroidism 5. Inc. TBG 6. Dec. TBG

Answer 227

1. Graves - -Inc. T4, FT4, dec. TSH, inc. uptake 2. Excess hormone - -Inc. T4, FT4, dec. TSH, dec. uptake 3. Primary hypothyroidism - -dec. T4, FT4, Inc. TSH, no change uptake 4. Secondary hypothyroidism - -dec. T4, FT4, TSH, no change 5. Inc. TBG - -inc. ST4, N, N, N 6. Dec. TBG - -dec. ST4

Question 228

Thyroid: The MC cause of goiter in developing countries is _____. Development occurs as a result of a repeating cycle of hyperplasia/hypertrophy and involution. Initially there is absolute/relative hormone deficiency. This deficiency leads to hyperplasia/hypertrophy of the gland (inc. production to compensate for lack). Ultimately, involution occurs due to failure of the gland to inc. hormone synthesis.

Answer 228

Iodine deficiency *initially diffuse enlargement -- multi-nodilar enlargement

Question 229

Thyroid: Goiter is a clinical and anatomic term. It does not ID hyper or hypofunctioning of the thyroid gland. True/False - Potential complications of a goiter include toxic nodular goiter (1 or more nodules become autonomous - "hot"), hoarseness, dyspnea and/or hemorrhage into cysts.

Answer 229

True NOTE: either TSH, free T3 and T4 OR clinical effects are required for detection and classification of disease

Question 230

Thyroid: Discovery of a goiter (via PE or ultrasound) with multiple nodules may be associated with either multinodular goiter or Hashimoto. What testing should be performed? How does this compare with solitary nodule?

Answer 230

1. Multiple nodules: - -Thyroid lab testing 2. Solitary (cyst/neoplasm): - -thyroid lab excludes clinical thyroid disease - -consider fine needle biopsy * most benign; "cold" - non-functioning

Question 231

Thyroid: ______ is a benign, solitary, "cold" nodule often surrounded by a complete capsule. It is the most common thyroid neoplasm.

Answer 231

Follicular adenoma

Question 232

Thyroid: Risk factors Thyroid Cancer include: 1. Ionizing radiation (e.g. papillary carcinoma; lymphoma) 2. Hashimoto (chronic lymphocytic thyroiditis (inc. risk non-Hodgkin B cell lymphoma) What are risk factors for malignancy within a thyroid nodule? a. history of head/neck irradiation b. family history of thyroid cancer c. age (<20; >70) d. firm or hard consistency

Answer 232

all of the above * papillary - any age * lymphadenopathy * non-mobile (fixed) * male * growing nodule * sonography - vascular flow, calcifications, heterogeneity

Question 233

Thyroid: _______ is the MC thyroid cancer. It is associated with ionizing radiation and is MC in females. It is known to spread through the lymph to the cervical lymph nodes. Features include: 1. Psamoma bodies (dystrophically calcified tumor cells) 2. Orphan Annie nuclei (overlapping nuclei with grooves). 3. RET and BRAF mutations

Answer 233

Papillary thyroid carcinoma Tx: -thyroidectomy and radioiodine ablation Prognosis: -very good even with metastasis Features: --RET and BRAF mutations

Question 234

Thyroid: A 17 year old female presents to the clinic for labs. Her labs reveal: 1. psammoma bodies 2. nuclear clearing, crowding and grooves Imaging reveals: 1. metastasis to the neck lymph nodes You suspect

Answer 234

papillary thyroid carcinoma * any age (>15 MC) * psammoma - not specific to PTC *amenable to ultrasound w/ fine needle aspiration for Dx (different echogenicity pattern; cytologic features with good specificity)

Question 235

Thyroid: There are 4 histologic types of thyroid carcinoma: 1. Papillary carcinoma (MC) 2. Follicular carcinoma 3. Medullar carcinoma 4. Anaplastic carcinoma ___ is the 2nd most common thyroid cancer occurring more often in females than males. It spreads hematogenously to the lung and bone. Nodal metastasis is less common. It is associated with RAS and PAX8-ppar Y mutations.

Answer 235

Follicular carcinoma Tx: --total thyroidectoma + radioactive iodine Prognosis: --PTC > follicular > anaplastic

Question 236

Thyroid: There are 4 histologic types of thyroid carcinoma: 1. Papillary carcinoma (MC) 2. Follicular carcinoma 3. Medullary carcinoma 4. Anaplastic carcinoma ____ is uncommon, and occurs most often in elderly. It is a highly malignant, rapidly growing tumor that is fatal within months. Its rapid growth can lead to emergent airway obstruction, causing dyspnea and dysphagia.

Answer 236

Anaplastic carcinoma *TP53 mutations

Question 237

Thyroid: _____ is a malignancy of C (parafollicular cells). It is most often sporadic, and may be inherited in an autosomal dominant fashion as part of MEN 2A or 2B syndrome. It results in increased calcitonin levels and C-cell hyperplasia.

Answer 237

Medullary carcinoma * inc. calcitonin (leads to dec. Ca2+) * can be converted to amyloid

Question 238

Thyroid: Both MEN2A and MEN 2B are associated with a RET mutation. Distinguish between MEN 2A and MEN 2B with regard to associated diseases

Answer 238

1. Men 2A --primary HPTH, medullar carcinoma, pheochromocytoma (thyroid and parathyroid tumors) 2. MEN 2B - -medullary carcinoma, pheochromocytoma, mucosal neuromas NOTE: pheochromocytoma = MC adrenal medulla tumor in adults. Derived from chromaffin cells (NCCs).

Question 239

Thyroid: A 64 year old female presents with a rapidly growing neck mass. She complains of dysphagia. You note hoarseness when she speaks and are concerned about compression of the trachea. Additional signs/symptoms include diffuse thyroid enlargement, regional lymph node enlargement and hypothyroidism. Flow cytometry reveals monolconal B cells. You suspect

Answer 239

Lymphoma * cold nodule * MC diffuse large B cell lymphoma, marginal zone B cell (MALT) or combo * *co-occurs with Hashimoto

Question 240

Thyroid: _______ may be used to evaluate thyroid nodules as it is relatively inexpensive and sensitive for detection of neoplasms in appropriate context. It is often performed with ultrasound guidance. It has good specificity for papillary thyroid carcinoma, and is excellent for demonstrating cyst contents or colloid (benign Dx).

Answer 240

Fine needle aspiration biopsy

Question 241

Thyroid: True/False - The Bethesda system provides a standardized screening reporting system for thyroid neoplasms. It is analogous to uterine cervix cytology methods. There are also Molecular assays exist to further triage atypical diagnosis

Answer 241

True categories: *benign atypical, suspicious for neoplasm, suspicious for malignancy, malignant

Question 242

Thyroid pharm: ____ is the best choice for long term replacement therapy (management) of hypothyroidism.

Answer 242

Levothyroxine (T4) Adverse: --tachycardia, weight loss, inc. insomnia,

Question 243

Thyroid pharm: _______ (T3) is also used as a form of replacement therapy. It has shorter action, but is more potent than T4, but poses a higher risk of hyperthyroidism symptoms

Answer 243

Liothyronine (T3)

Question 244

Thyroid pharm: Replacement therapy using a mixture of of T4:T3 (4:1) is only used in cases of persistent ______ on T4

Answer 244

hypothyroidism

Question 245

Thyroid: Thyroid replacement therapy improves metabolic processes (protein synthesis, fat catabolism, and use of glucose for energy). It also increases growth, development and nerve excitability. T4 has a slower onset (3-5 days) than T3 (2-4hr) but has a longer duration of action via enterohepatic circulation (liver metabolism). With regard to peripheral metabolism, which is the most active?

Answer 245

T3 is most active T4 converted to T3

Question 246

Thyroid: 1. ______ is a drug that acts to reduce T4/T3 absorption and efficacy. 2. ______ are drugs that increase T4/T3 metabolism and thus, dec. their efficacy. 3. ______ and ______ decrease conversion of T4 to T3

Answer 246

1. Sucralfate 2. Anti-seizures 3. Anti-arrhythmics (amiodarone and glucocorticoids)

Question 247

Thyroid: What are adverse effects of T3/T4? a. Insomnia b. Tachycardia c. Tremors d. Inc. bleeding

Answer 247

A - C

Question 248

Thyroid: Which of the following is a contraindication for the use of T3/T4 replacement therapy? a. acute MI b. COPD c. Adrenal insufficiency d. Pregnancy

Answer 248

A, C, D 1. Acute MI -- worsens symptoms 2. Adrenal: inc. risk acute adrenal crisis (not enough cortisol; life threatening 3. Pregnancy: T3 mainly

Question 249

Thyroid: Anti-thyroid agents include 1. Iodine compounds 2. Radioactive iodide 3. Methimazole and propylthiouracil (long-term effects) _____ are only for short term use (~2 weeks). They are commonly used in preparation for thyroid surgery or for thyroid storm (severe life-threatening hyperthyroidism).

Answer 249

Iodide compounds (short term effects)

Question 250

Thyroid: True/False - Organic agents (Iopanoic acid or ipodate sodium) are used more commonly as anti-thyroid medications than are iodine agents (KI, Lugol's solution)

Answer 250

True

Question 251

Thyroid: Iodides prevent _____ synthesis, hormone release, and conversion of T4 to T3 (most active).

Answer 251

thyroglobulin synthesis

Question 252

Thyroid: Radioactive iodide may be used as long-term therapy. Clinical uses of radioactive 131 Iodide (after single treatment) include: 1. Graves disease 2. Inoperable thyroid cancer 3. Multinodular goiter 4. Recurrent thyrotoxicosis 5. Determine thyroid function What is the mechanism of action of radioactive Iodide?

Answer 252

1. Ingestion -- traps 131 Iodide within the thyroid gland - -destroys follicular cells (strong Beta emission) - -dec. T3/T4 production 2. Shrinks glands after ~3 months

Question 253

Thyroid: Side effects of Radioactive Iodide are radioactive contamination (several weeks) and follicular cell destruction (hypothyroidism - use T4). True/False - Prior to being treated with 131 I, patients must STOP taking T4/T3, methimazole, propylthiouracil or iodide compounds.

Answer 253

True **1-2 weeks prior to 131 I administration Cx: --Pregnancy, Lactation

Question 254

Thyroid: Anti-thyroid agents include 1. Iodine compounds 2. Radioactive iodide 3. Methimazole and propylthiouracil Methimozaole and Propylthiouracil may be used for long term continuous management of Graves disease, nodular goiter, and thyrotoxicosis. It may also be used for short term (surgery). When is propylthiouracil used?

Answer 254

ONLY when methimazole does not work NOTE: these are thioamides

Question 255

Thyroid: True/False - Both Methimazole and Propylthiouracil prevent hormone synthesis via irreversible inhibition of thyroid peroxidase (TPO). However, only propylthiouracil (PTU) blocks conversion of T4 to T3.

Answer 255

True

Question 256

Thyroid: Methimazole is an anti-thyroid med that is more potent, faster acting, and has a longer duration compared to PTU. It also has fewer side effects (e.g. hepatotoxicity) than PTU. Which of the following is a drug interaction? a. anti-coagulants b. B-blockers c. anti-hypertensives d. anti-psychotics

Answer 256

A and B 1. Drug interactions - -Anti-coagulants (warfarin) = inc. risk bleeding - -B-blockers = inc. side effects 2. Contraindications - -Pregnancy: only PTU use in 1st trimester - -Methimazole: only in the 2nd and 3rd trimesters

Question 257

Thyroid: B-blockers may be used to improve the adrenergic symptoms associated with hyperthyroidism. The MC B-blockers used are: 1. Propanolol (**thyrotoxicosis) 2. Metoprolol 3. Atenolol These drugs act by blocking B-adrenoceptors in the CV system reducing tachycardia, HTN and tremors. They also inhibit the conversion of T4 to T3. Describe their pharmacokinetics

Answer 257

1. Duration - -atenolol: long - -propanolol/metoprolol: medium 2. Liver metabolism - -CYP

Question 258

Thyroid: B-blockers may be used to improve the adrenergic symptoms associated with hyperthyroidism. The MC B-blockers used are: 1. Propanolol (**thyrotoxicosis) 2. Metoprolol 3. Atenolol List the side effects associated with these drugs

Answer 258

1. Bronchoconstriction 2. Hypotension 3. Inc. blood glucose

Question 259

Thyroid: B-blockers may be used to improve the adrenergic symptoms associated with hyperthyroidism. The MC B-blockers used are: 1. Propanolol (**thyrotoxicosis) 2. Metoprolol 3. Atenolol B-blockers tend to mask the effect of anti-diabetic medications. They also interact with drugs that modify CYP enzymes. What are contraindications for these drugs?

Answer 259

1. Asthma/COPD 2. Heart dysfunction 3. Diabetes *mask hypoglycemia symptoms (hide tremors, palpitations) making it difficult to ID hypoglycemic episodes

Question 260

Physio: Cold stress is a stimulator of thyroid hormone. It acts by stimulating TRH which ultimately leads to increased T3/T4 and inc. metabolic rate and body temperature. How is overheating prevented?

Answer 260

1. removes and dec. cold stimulus | 2. T3/T4 -- negative feedback to hypothalamus and ant. pituitary

Question 261

Physio: List the functions of thyroid hormone

Answer 261

4 B's Brain/CNS maturation Bone growth/formation B-adrenergic (inc. CO) Inc. Basal metabolism (Na/K ATPase) *TRE = protein synth -- LDL, B-adrenergic receptors, hormones, vitamins (turnover)

Question 262

Physio: What are the inhibitors of Thyroid hormone? Stimulators?

Answer 262

1. Inhibition - -Iodine deficiency - -T3/T4 - -dec. TBG - -Na/I or peroxide antagonists 2. Stimulate - -IgGs - -inc. TBG - -stress

Question 263

Physio: Prolactin functions in milk production and release. It is stimulated by suckling. What are its effects on breast tissue (lactocytes)? How is milk delivered?

Answer 263

1. Lactocytes - -proliferate; inc. milk production - -duct proliferation 2. Milk delivery - -oxytocin = contract myoepithelial cells NOTE: PRL inhibitis GnRH

Question 264

Physio: Thyroglobulin is a protein made in the thyroid gland that serves as the precursor to thyroid hormone. Review the steps in Thyroid hormone formation

Answer 264

1. Thyroglobulin in colloid 2. Iodide uptake into follicular cells via NaI 3. Iodidie converted to Iodine (thyroid perox) 4. Tyrosine residues are iodinated (1 iodine = MIT; 2 = DIT) 5. Coupling of tyrosine residues (MIT + DIT = T3; DIT + DIT = T4) 6. Stored in colloid bound to TG for up to 3 months 7. TSH release --- cAMP -- movement of stored TG into follicular cells 8. Lysosomal enzymes breakdown TG - free T3/T4 9. Diffuse across membrane into blood 10. bound in blood to thyroxine binding globulin

Question 265

Physio: T4 is converted to T3 in target tissue by what enzyme?

Answer 265

type I deiodinase

Question 266

Adrenal Histo: The adrenal (suprarenal) gland is a retroperitoneal structure that is located between the diaphragm and the superomedial kidney. It is surrounded by CT and peripnephric fat. Its shape differs on two sides, the right gland is _____ shaped and more apical, while the left gland is _____ shaped.

Answer 266

1. Right side - --pyramidal 2. Left side - -crescent

Question 267

Adrenal Histo: The _______ is the site of the gland where veins and lymphatic vessels exit. Arteries and nerves enter the glands at multiple sites.

Answer 267

Hilum

Question 268

Adrenal Histol: The adrenal gland has one of the highest arterial flow rates/gram of tissue. Each gland is supplied by 3 arteries: 1. Superior suprarenal artery 2. Middle suprarenal artery 3. Inferior suprarenal artery ________ arises from the inferior phrenic artery and enters the gland as 4-5 small branches. It can occasionally arise from the abdominal aorta.

Answer 268

Superior suprarenal artery

Question 269

Adrenal Histol: The adrenal gland has one of the highest arterial flow rates/gram of tissue. Each gland is supplied by 3 arteries: 1. Superior suprarenal artery 2. Middle suprarenal artery 3. Inferior suprarenal artery The middle suprarenal arises from the abdominal aorta, while the inferior suprarenal artery arises from the ________ or _______.

Answer 269

Inferior: abdominal aorta or gonadal artery *supplies most of arterial blood to adrenals

Question 270

Adrenal Histo: The central vein exits the adrenal hilum and forms the suprarenal vein. 1. _______ is short and drains into the IVC 2. ______ is longer, descending medially and draining into the left renal vein (sometimes drains into left phrenic vein)

Answer 270

1. Right suprarenal vein | 2. Left suprarenal vein

Question 271

Adrenal Histo: Lymph exits the adrenal gland via _____ lymphatic vessels that ultimately drain medially to lumbar lymphatic nodes.

Answer 271

subscapular lymph vessels

Question 272

Adrenal Histo: The adrenal gland has large autonomic nerve supply. 1. Sympathetic pre-ganglionic cholinergic (thoracic splanchnic nerves) synapse on _________ 2. Post-ganglionic sympathetic nerves innervate ______ blood vessels and regulate blood flow.

Answer 272

1. medullary (chromaffin) cells | 2. cortical blood vessels

Question 273

Adrenal Histo: 1. The medullary cells of the adrenal gland arise from _______ that migrate from nearby sympathetic ganglia 2. Cortical cells arise from ______, which divide and give rise to fetal cortex cells. These cells surround the developing medulla. 3. Later, a second migration of ______ cells will surround the mass of fetal cortex and medullary cells. This second migration leads to the permanent cortex.

Answer 273

1. NCC's 2. mesodermal mesenchyme 3. mesenchymal cell migration

Question 274

Adrenal Histo: At 7 months, the permanent cortex forms around the fetal cortex. At birth, the fetal cortex undergoes ________ while the permanent cortex continues to develop, ultimately forming the adult cortex.

Answer 274

involution NOTE: fetal adrenal gland has medullary cells, but not definitive medulla

Question 275

Adrenal Histo: The fetal adrenal gland produces _____ steroid hormones/day compared to the adult. It functions with the placenta

Answer 275

2x

Question 276

Adrenal Histo: The adrenal medulla has dual blood supply: 1. Arterial blood from ________ 2. Venous blood from _______, which picks up secretions from each layer.

Answer 276

1. medullary arterioles | 2. cortical sinusoidal capillaries

Question 277

Adrenal Histol: Specific hormones are synthesized in specific zones of the adrenal cortex due to presence/absence of enzymes. However, all zones contain ________ the rate limiting enzyme in each of these pathways (steroid hormones). This enzyme is stimulated by ACTH

Answer 277

Cholesterol desmolase NOTE: aldosterone synthesis from corticosterone requires Ang. II stimulation (aldosterone synthase)

Question 278

Adrenal Histo: Which zone of the adrenal cortex contains aldosterone synthase?

Answer 278

Zona glomerulosa Corticosterone to Aldosterone via aldosterone synthase (Ang. II stimulus)

Question 279

Adrenal Histo: What enzyme is involved in the formation of both cortisol and dehydroepiandrosterone?

Answer 279

17, 20 lyase

Question 280

Adrenal Histo: ______ is the outermost layer of the adrenal cortex beneath the CT capsule. It is characterized by the presence of small columnar ("ball"-like) cells with spherical nuclei arranged in cords and clusters. These cell clusters are surrounded by a network of fenestrated capillaries.

Answer 280

Zona glomerulosa * lots of sER, mitochondria, and triglycerides * Aldosterone (mineralcorticoids)

Question 281

Adrenal Histo: Which of the following is a function of aldosterone? a. Inc. urea recycling b. Inc. Na2+ reabsorption and K+ excretion in CD c. Inc. Na2+ absorption in gastric mucosa d. Inc. Na2+ resorption in salivary and sweat glands

Answer 281

B-D

Question 282

Adrenal Histo: Aldosterone is regulated by the RAAS system. It is secreted in response to dec. b.p. or low blood Na2+ levels. These changes are detected by ______ cells of the kidney, resulting in renin release.

Answer 282

JG cells Antiotensinogen --- Ang I (via renin) Ang I --- Ang II (ACE in lungs) Ang II = aldosterone secretion Inc. b.p., blood volume, Na2+ conc.

Question 283

Adrenal Histo: You receive a tissue sample containing large, vacuolated cells arranged in long, straight cords. These are 1-2 cells thick, with lots of lipid droplet present. What tissue does this describe?

Answer 283

Zona fasciculata * long straight cords 1-2 cells thick * lots of lipid droplets, sER

Question 284

Adrenal Histo: Fasciculata cells release glucocorticoids (cortisol, corticosteroids, gonadocorticoids). True/False - These hormones are NOT stored within the fasciculata cells. Hormonal increase requires new hormone synthesis

Answer 284

True

Question 285

Adrenal Histo: Cortisol is a steroid hormone that is secreted in a pulsatile manner (via pulsatile secretion of ACTH). It peaks just before waking. Which of the following is a function of cortisol? a. Inc. gluconeogenesis (liver) b. Inc. lipolysis (adipose) c. Muscle wasting (aa generation) d. Bone resorption e. Dec. immune and inflammation (dec. wound healing)

Answer 285

all of the above BIG FIB - -inc. blood pressure (CO) - -inc. insulin resistance (inhibits insulin-mediated glucose uptake by muslce/fat) - -inc. gluconeogenesis - -dec. fibroblasts - -dec. inflammation/immunity - -dec. bone formation

Question 286

Adrenal Histo: Cells in this layer of the adrenal gland appear smaller and darker with lipofuscin (and fewer lipid droplets). The change in staining appearance is a distinguishing feature of this layer.

Answer 286

Reticularis * pyknotic nuclei near medulla -- degenerating cells * anastamosing cords

Question 287

Adrenal Histo: The zona reticularis is responsible for the secretion of gonadocorticoids (and small amounts of cortisol). These are weak androgens with negligible effects under normal conditions (<1/5 potency of testicular androgens). What is the major secretion?

Answer 287

**DHEA (dehydroepiandrosterone) | androstendione

Question 288

Adrenal Histo: The adrenal medulla is the central region of the adrenal gland. It is enclosed by cortex. It develops from ectodermal NCC's and is arranged in short, irregular cords surrounded by a capillary network. What is a major feature of the adrenal medulla?

Answer 288

1. Ganglion cells - -axons extend to cortex - -regulate activity of cortical cells and innervate blood vessels - -also extend to splanchnic nerves outside gland

Question 289

Adrenal Histo: The adrenal medulla is composed of ganglion cells and medullary (chromaffin) cells. Chromaffin cells are modified neurons that lack axonal processes. They appear as large, basophilic cells. These cells are responsible for the storage of

Answer 289

catecholamines * modified neurons (post-synaptic sympathetic) * lack axonal processes (due to glucocorticoids from cortex)

Question 290

Adrenal Histo: Medullary cells are modified post-synaptic neurons that lack axonal processes. They contain NE and E. 1. ____ is secreted in response to emotional stimulus 2. _____ is secreted in response to physiologic (pain) stimulus

Answer 290

1. NE - emotional 2. E - pain (fight or flight) *Ach depolarizes membrane - splanchnic nerves

Question 291

Adrenal Histo: Glucocorticoids from the cortex travel to the medulla and inc. expression of enzyme that can catalyze the methylation of NE to Epinephrine (in response to stress). Explain the process

Answer 291

1. Tyrosine - --Tyrosine Hydroxylase 2. DOPA - -dopamine decarboxy 3. Dopamine - -dopamine B-hydroxy 4. NE - -PMNT + Cortisol 5. Epinephrine

Question 292

Adrenal Histo: Epinephrine and NE exert their functions via binding to alpha and beta adrenergic receptors. Effects are sympathomimetic (similar to sympathetic ANS). Which of the following is a function of these hormones? a. Inc. heart rate and b.p. b. dec. blood flow to viscera/skin c. induce conversion of glycogen to glucose d. inc. sweating

Answer 292

all of the above * bronchodilation * inc. respiration * dec. digestion and urine

Question 293

Adrenal path: Adrenal cortical hormones are synthesized from LDL cholesterol. 1. CRH is secreted in response to low plasma cortisol and stress. This induces the release of ACTH (corticotropin) which stimulates ______ enzyme in the adrenal cortex to produce POMC. Cleavage of POMC ultimately leads to MSH, ACTH and B-endorphins.

Answer 293

cholesterol desmolase MSH: melanocyte stim. hormone - -structurally similar to ACTH - -skin and mucous membrane pigmentation ACTH: - -stimulates production of mineralcorticoids (aldosterone precursors) - -glucocorticoids - -androgens (DHEA and testosterone)

Question 294

Adrenal path: True/False - ACTH has NOT efect on the adrenal medulla.

Answer 294

True NOTE: excess ACTH - adrenocortical hyperplasia; deficiency -- adrenal atrophy

Question 295

Adrenal path: ACTH stimulates cholesterol desmolase to convert cholesterol to pregnenolone. From here, pregnenolone can form 1. Corticosterone (aldosterone precursor) 2. Cortisol 3. Dihydrotestosterone (DHT)

Answer 295

FINISH *slide 4

Question 296

Adrenal path: Cushing syndrome is an umbrella term used to describe states of excess cortisol. There are 2 types of Cushing syndrome: 1. ACTH dependent 2. ACTH independent ACTH dependent Cushing syndrome is characterized by the presence of something secreting ACTH (which is inducing high cortisol). What are common ACTH-dependent causes of Cushing?

Answer 296

``` 1. Pituitary Adenoma (Cushing disease) --MCC endogenous Cushing syndrome --ACTH MC than ACTH independent --Labs: Inc. ACTH, Inc. cortisol ``` 2. Paraneoplastic Cushing - -Ectopic secretion of ACTH - -MC small cell carcinoma - -Labs: Inc. ACTH and cortisol **bilateral adrenal hyperplasia in both

Question 297

Adrenal path: Cushing syndrome is an umbrella term used to describe states of excess cortisol. There are 2 types of Cushing syndrome: 1. ACTH dependent 2. ACTH independent ACTH independent Cushing syndrome is characterized by

Answer 297

1. Exogenous steroids - -MCC of Cushing syndrome - -bilateral adrenal atrophy - -dec. ACTH, Inc. cortisol 2. Adrenal Cushing Syndrome - -adrenal adenoma - -rare - -dec. ACTH, inc. cortisol - -single adrenal gland is enlarged (other unaffected atrophies) **both = adrenal atrophy

Question 298

Adrenal Path: ACTH dependent Cushing syndrome includes: 1. Pituitary adenoma (secreting ACTH) 2. Ectopic ACTH (small cell lung cancer) These disorders would present with diffuse hyperplasia of the adrenal gland, compared to ACTH independent (e.g. exogenous steroids) which would present with

Answer 298

atrophy of the adrenal gland

Question 299

Adrenal Path: An obese female presents with the complaint of muscle weakness (atrophy). General appearance includes buffalo hump, moon facies with inc. facial hair (hirsutism) and thinning of the scalp hair. She has dark purple abdominal stria, and thin wrinkled skin. She has dark purple abdominal stria with thin wrinkled skin. She admits to depressed mood and difficulty sleeping. Medical history is significant for Glaucoma, Exopthalmos (due to retro-orbital fat) and HTN. You suspect

Answer 299

Cushing syndrome - enlarged sella turcica - dec. LH, FSH, GH, TSH - insulin resistance Associated: - inc. CV mortality - risk peptic ulcers

Question 300

Adrenal Path: A 36 year old female presents to the office with complaints of fatigue, weakness and mass on her back. PE reveals truncal obesity with a soft tissue enlargement (buffalo hump) on the posterior neck and shoulders. There are purple striae on the abdomen. Labs reveal: 1. Hyperglycemia (elevated blood glucose) 2. Hypokalemia (inc. mineralcorticoid) 3. Metabolic alkalosis (inc. mineralcorticoid activity) 4. Inc. WBC (demargination) You suspect Cushing syndrome. What is the MCC?

Answer 300

MCC - exogenous oral corticosteroids (prednisone) **high suspicion in px w/ long term steroid use (autoimmune diseases, TTP) NOTE: CV risk due to salt/water retention - inc. mortality; also inc. insulin resistance and diabetogenic effect

Question 301

Adrenal Path: A 36 year old female presents to the office with complaints of fatigue, weakness and mass on her back. PE reveals truncal obesity with a soft tissue enlargement (buffalo hump) on the posterior neck and shoulders. There are purple striae on the abdomen. Labs reveal: 1. Hyperglycemia (elevated blood glucose) 2. Hypokalemia 3. Metabolic alkalosis (inc. mineralcorticoid activity) 4. Inc. WBC (demargination) How do you treat?

Answer 301

Tx: 1. If exogenous cortisol -- TAPER patients off steroids * failure to taper = acute adrenal insufficiency 2. Pituitary tumor - -trans-sphenoidal surgery 3. Adrenal adenoma/carcinoma - -adrenalectomy

Question 302

Adrenal Path: True/False - Once a patient has been diagnosed with Cushing syndrome, then ACTH may be measured to determine if it is ACTH dependent (e.g. pituitary adenoma or ectopic ACTH) or independent (exogenous steroids or adrenal hyperplasia) to determine the specific cause.

Answer 302

True

Question 303

Adrenal Path: A p45 y/o male presents with past surgical history bilateral adrenalectomy for refractory Cushing disease. He complains of dark skin changes (hyperpigmentation), headache and vision changes (bitemporal hemianopsia). You suspect

Answer 303

Nelson syndrome * disorder is 2ndary to Tx of Cushing (adenoma) * due to bilateral adrenalectomy

Question 304

Adrenal Path: Ang II. has the following functions: 1. Constriction of the efferent arteriole (inc. GFR) 2. Stimulates 18-hydroxylase (stimulate aldosterone) 3. Inc. ADH release (thirst center) Other: 4. Potentiates NE release via direct action on post-ganglionic symp. fibers 5. Inc. ACTH release 6. Platelet adhesion and aggregation What is the function of aldosterone?

Answer 304

1. Acts on principal cells (DCT and CD) - -inc. Na and water - -K+ secretion (inc. basolateral Na/K+ pumps) 2. Acts on alpha intercalated cells - -excretion of H+ ions 3. Inc. Na/water reabsorption from gut, saliva and sweat - -dump K+ - -inc. Cl in conjunction w/Na2+ (maintain electrochemical balance) *metabolic alkalosis

Question 305

Adrenal path: A patient presents with complaints of headache. He states he has noticed increased muscle weakness and fatigue. On PE you note facial flushing. Patient admits to constipation. EKG reveals: 1. prominent U wave Labs reveal: 1. Inc. Na2+ (hypernatremia) 2. Dec. K+ (hypokalemia) 3. Metabolic alkalosis 4. Dec. Plasma Renin 5. Inc. aldosterone You suspect

Answer 305

Hyperaldosteronism * may be asymptomatic early on * symptoms usually associated with HTN (severe; Na retention) and hypokalemia Severe: hypertensive encephalopathy (visual impairment, impaired consciousness, seizures)

Question 306

Adrenal path: A patient presents with complaints of headache. He states he has noticed increased muscle weakness and fatigue. On PE you note facial flushing. Patient admits to constipation. EKG reveals: 1. prominent U wave Labs reveal: 1. Inc. Na2+ (hypernatremia) 2. Dec. K+ (hypokalemia) 3. Metabolic alkalosis 4. Dec. Plasma Renin 5. Inc. aldosterone You suspect Hyperaldosteronism. What is the pathogenesis

Answer 306

Excessive secretion of aldosterone * Inc. Na2+ reabsorption * Dec. K+ and H+ ions * Plasma volume expansion = suppressed renin NOTE: renovascular HTN would have Inc. Renin

Question 307

Adrenal path: A patient presents with complaints of headache. He states he has noticed increased muscle weakness and fatigue. On PE you note facial flushing. Patient admits to constipation. EKG reveals: 1. prominent U wave Labs reveal: 1. Inc. Na2+ (hypernatremia) 2. Dec. K+ (hypokalemia) 3. Metabolic alkalosis 4. Dec. Plasma Renin 5. Inc. aldosterone Primary hyperaldosteronism is MC associated with issues with the adrenal gland. Examples of this include: bilateral adrenal hyperplasia (MC) and adrenocortical adenoma (Conn syndrome). Secondary hyperaldosteronism occurs secondary to kidney secreting excess renin. What is a common cause of secondary?

Answer 307

1. Renal artery stenosis | - -dec. renal blood flow (see inc. plasma renin)

Question 308

Adrenal Path: Patients with hypokalemia most often present with what complaints/symptoms?

Answer 308

-muscle weakness and fatigue (changes in K+ membrane potential) --U waves --Constipation

Question 309

Adrenal Path: A patient presents with complaints of muscle weakness. You note depressed/absent deep tendon reflexes. ECG shows peaked T waves Current meds: Lisinopril daily You suspect

Answer 309

Hypoaldosteronism 1. Hyperkalemia - -peaked T waves (inc. repol. of cardiac muscle) - -reflexes (partial depol. of cell membrane; dec. excitation)

Question 310

Adrenal Path: A patient presenting with hypoaldosteronism (both types) has a high risk of cardiac arrest due to

Answer 310

ventricular dysrhythmia (severe hyperkalemia - 7-8mEq/L) *heart stop in diastole

Question 311

Adrenal Path: Hypoaldosteronism can be categorized based on the renin levels: 1. Hyporeninemic hypoaldosteronism 2. Hyperreninemic hypoaldosteronism _____ causes dec. production of aldosterone due to dec. production of renin. Most often due to secondary renal disease (diabetes, interstitial nephritis, nephrotic syndrome)

Answer 311

Hypereninemic hypoaldosteronism

Question 312

Adrenal Path: Hypoaldosteronism can be categorized based on the renin levels: 1. Hyporeninemic hypoaldosteronism 2. Hyperreninemic hypoaldosteronism ____ is dec. production of aldosterone, but renin production remains normal. Causes include medications (ACE inhibitors), lead poisoning, and enzyme deficiency (for aldosterone synthesis)

Answer 312

Hyperreninemic

Question 313

Adrenal path: Adrenocortical insufficiency can be categorized as acute vs. chronic. True/False - Acute may be due to sudden necrosis or hemorrhage (septic shock), abrupt withdrawal of exogenous corticosteroid, and/or blockage of an enzyme involved in production

Answer 313

True 1. Abrupt withdrawal corticosteroid (MCC) - -failure to taper (etomidate - anesthetic; prednisone) 2. Necrosis/hemorrhage 3. Blocked enzyme

Question 314

Adrenal path: Adrenocortical insufficiency can be categorized as acute vs. chronic. What is the MC cause of Chronic insufficiency?

Answer 314

1. Autoimmune destruction (MC in U.S.) - -abs to steroidogenic enzymes (21-hydroxylase MC) - -all 3 zones of adrenal cortex (entire cortex destroyed --- dec. mineralcorts and glucorts) 2. Mycobacterial destruction (developing world) - -disseminated TB or Histoplasmosis 3. Congenital adrenal hyperplasia 4. Metastasis 5. HIV 6. Hemochromatosis

Question 315

Adrenal path: Acute primary adrenal insufficiency due to bilateral adrenal hemorrhage (or infarction). It is caused by septicemia induced by N. meningitidis

Answer 315

Waterhouse-Friderichsen syndrome *sepsis due to bacterial endotoxin

Question 316

Adrenal path: A patient presents with low blood pressure (hypotension), fatigue and weakness (maybe hypoglycemia). Physical exam reveals diffuse hyperpigmentation of skin/skin folds and buccal mucosa. Admits to orthostasis. Labs reveal: 1. Dec. cortisol (dec. total serum cortisol) 2. Inc. ACTH 3. Hypoglycemia (cortisol is gluconeogenic) 4. dec. Na2+ and dec. K+ 5. Metabolic acidosis (H+ retained) You perform an ACTH stimulation test (cosyntropin). There was no inc. in cortisol following administration of cosyntropin. This confirms your suspicion that your patient has ______

Answer 316

Addison disease (CHRONIC adrenocortical insufficiency) * primary adrenal insufficiency (at adrenal gland) * Na2+ loss NOTE: Be sure to address other possible dysfunctions along HPA axis (TB, surgery)

Question 317

Adrenal path: True/False - Patients with Adrenocortical insufficiency typically present with hyperpigmentation of the skin and mucous membranes due to inc. ACTH and MSH production. This occurs from lack of negative feedback of cortisol (adrenal gland destroyed).

Answer 317

True

Question 318

Adrenal path: Secondary adrenal insufficiency is a chronic disorder due to failure of the pituitary gland (secondary) to produce ACTH. This leads to dec. cortisol synthesis. Patients may have global pituitary dysfunction (e.g. hypothyroidism and hypogonadism). Although there is a lack of ACTH, what may be spared?

Answer 318

1. Aldosterone - -RAAS intact - -no hyperkalemia in these px 2. Secondary spares the skin/mucosa - -dec. ACTH

Question 319

Adrenal path: What are common etiologies of secondary adrenocortical insufficiency?

Answer 319

1. Pituitary/Hypothalamic tumor 2. Sarcoidosis 3. Hemochromatosis

Question 320

Adrenal path: ____ is a group of autosomal recessive genetic diseases characterized by one or more adrenal cortex enzyme deficiencies involved in the synthesis of cortisol. This results in continuous stimulation of the adrenal cortex by ACTH.

Answer 320

Congenital adrenal hyperplasia * dec. cortisol = no feedback = inc. ACTH * build up of steroid precursors behind the defective step (inc. androgen production -- virilization)

Question 321

Adrenal Path: True/False - *When a newborn (female) presents with ambiguous genitalia, the 1st thing to do is to check the genetic sex of the newborn using a chromosome analysis. Male infants may have enlarged penises, but do not develop ambiguous genitalia.

Answer 321

True

Question 322

Adrenal path: A female presents with ambiguous genitalia. She exhibited rapid growth during childhood, with early fusion of the epiphyses. Additional symptoms include: 1. salt wasting (mineralcorticoid deficiency) 2. hyponatremia 3. hyperkalemia 4. hypotension 5. cardiovascular collapse Labs: 1. dec. cortisol, inc. ACTH You suspect

Answer 322

21 alpha hydroxylase insufficiency --can't convert progesterone to deoxycortisone (loss of mineralcorticoid effects) --also can't convert progesterone into 11-deoxycortisol (loss of cortisol effects) NOTE: precocious puberty in males; ambiguous genitalia females (due to inc. DHT)

Question 323

Adrenal path: A female presents with ambiguous genitalia. She exhibited rapid growth during childhood, with early fusion of the epiphyses. Additional symptoms include: 1. salt wasting (mineralcorticoid deficiency) 2. hyponatremia 3. hyperkalemia 4. hypotension 5. cardiovascular collapse What is a good screening test to perform?

Answer 323

17-hydroxyprogesterone (converts to androgen synthesis) * inc. 17-ketosteroids, testosterone and DHT * everything proximal to block is inc.

Question 324

Adrenal path: A male patient presents with enlarged penis (precocious puberty), early development of pubic hair, increased linear bone growth and accelerated bone age. Labs reveal: 1. Salt retention (HTN) 2. hypokalemia (11-deoxycortisone; low renin) 3. dec. cortisol 4. inc. ACTH

Answer 324

FINISH

Question 325

Adrenal path:

Answer 325

17 hydroxylase FINISH

Question 326

Adrenal path: The adrenal medulla is responsible for the production of catecholamines. The medulla arises from neural crest cells which form pheochromoblasts (chromaffin cells) and neuroblasts (ganglion cells; neurons). Catecholamines are synthesized from a tyrosine precursor and are metabolized either by catechol-O-methyltransferase (COMT) or ____

Answer 326

monoamine oxidase (MAO)

Question 327

Adrenal path: A 3 year old presents with palpable, firm, irregular abdominal mass that can cross the midline. Labs reveal: 1. Inc. urine homovanillic acid (HVA) and VMA (catecholamine metabolites) 2. Homer-Wright rosettes

Answer 327

Neuroblastoma * MC tumor of adrenal medulla in kids < 4 * NCC (neuroblast; pleuripotent) derived * anywhere along sympathetic chain (MC medulla)

Question 328

Adrenal path: A 3 year old presents with palpable, firm, irregular abdominal mass that can cross the midline. Labs reveal: 1. Inc. urine homovanillic acid (HVA) and VMA (catecholamine metabolites) Histology reveals: Homer-Wright rosettes Imaging reveals: Bilateral bone mets and Intravenous pyelogram You suspect Neuroblastoma. This is most associated with the overexpression of ______

Answer 328

Nmyc oncogene * unfavorable prognosis (better if < 1 y/o - less metastasis) * metastasis to skin, bone marrow, liver, bones, brain

Question 329

Adrenal path: A 35 year old female presents with complaints of "spells" of HA, palpitations (tachycardia), and diaphoresis. She suffers from severe HTN. She reports the frequency of the spells varies (monthly to several times daily) lasting seconds to hours. Over time, the spells have occurred more frequently and have become more severe. Labs reveal: 1. increased plasma free metanephrine and normetanephrine OR inc. catecholamines and metanephrines in 24 hr. urine and plasma. 2. Urine VMA (vanillylmandelic acid) 3. Hyperglycemia 4. Neutrophilic leukocytosis (demargination) You suspect

Answer 329

Pheochromocytoma * MC tumor of adrenal medulla in adults * 3rd - 5th decade * MEN 2a, MEN2b * arise from NCC's (chromaffin cells)

Question 330

Adrenal path: Pheochromocytoma follows the rule of 10's. 1. 10% malignant 2. 10% bilateral 3. 10% extra-adrenal (bladder, organ of Zucker) 4. 10% calcify 5. 10% kids These tumors typically secrete ______ which contributes to the episodic HTN and symptoms.

Answer 330

Epinephrine, NE** and Dopamine alpha receptor: --inc. b.p, inc. cardiac contractility, hyperglycemia (glycogenolysis and gluconeo), intestinal relaxation (ileus) B-receptor: inc. HR, inc. contractility

Question 331

Adrenal path: Pheochromocytoma can be exacerbated by drugs including metoclopramide, tricicylics and naloxone. True/False - It is also associated with RET, NF-1, VHL and SDHx mutations.

Answer 331

True

Question 332

Adrenal path: Surgery is definitive treatment for pheochromocytoma, however, the patient must be medically stabilized first. How is this done?

Answer 332

1. 1st --irreversible alpha blockade (phenoxybenzamine) 2. B-blockade *alpha 1st to avoid hypertensive crisis

Question 333

Adrenal path: Multiple endocrine neuroplasia (MEN) comes in different forms. A patient presenting with 1. Parathyroid hyperplasia 3. Pituitary adenoma (prolactinoma or GH/acromegaly) 4. Pancreatic endocrine tumors (aggressive, metastatic) What is the most likely mutation?

Answer 333

MEN 1 tumor suppressor * pancreas, pituitary, parathyroid * hyperparathyroidism (MC manifestation; initial symptom) * hypercalcemia

Question 334

Adrenal Path: A patient presents with a GOF mutation in RET proto-oncogene (germline, missense, or activating). His disorder has the following features: 1. Constitutive Tyrosine Kinase activity 2. Renal Stones 3. Inc. Calcitonin and C-cell hyperplasia He most likely has a mutation in

Answer 334

MEN 2A 1. Parathyroid Hyperplasia (renal stones) 2. Medullary Thyroid Carcinoma (multi-focal w/ C-cell hyperplasia; aggressive) 3. Pheochromocytoma (bilateral; extra-adrenal paragangliomas) NOTE: screen at risk family members

Question 335

Adrenal path: Medullary thyroid carcinoma is a malignancy of C (parafollicular) cells. It is usually sporadic, but may be inherited (AD) as part of MEN 2A or 2B syndrome. It is caused by a mutation in the _______, and results in excessive calcitonin production (tumor marker). It appears as cords and nests on histology.

Answer 335

RET proto-oncogene * inc. calcitonin = dec. calcium (dec. osteoclast) * amyloid * cords and nests on histo MEN2A: primary HPTH, meduallry CA, pheo

Question 336

Adrenal path: ____ is due to a point mutation in RET proto-oncogene. It results in constitutive tyrosine kinase activity and results in: 1. Mucosal neuromas 2. Marfanoid body habitus 3. Medullary thyroid carcinoma 4. Pheochromocytoma 5. Mucosal/GI ganglioneuromas

Answer 336

MEN2B *thyroid carcinoma: More aggressive than MEN2A

Question 337

Adrenal Pharm: Cushing's disease (inc. cortisol) may be treated with: 1. Cortisol synthesis inhibitors (Ketoconazole, Metyrapone, Mitotane) 2. GLucocorticoid receptor antagonists (Mifepristone w/ surgery for type II diabetes) 3. Somatostatin analogs (Pasireotide) Pasireotide is a somatostatin analog that is used as 2nd line treatment when surgery is not an option or fails. Pasireotide acts by activating ______ in the pituitary gland. This leads to dec. ACTH and thus, cortisol.

Answer 337

activates somatostatin receptors (SSTR) *inhibits ACTH and cortisol secretion

Question 338

Adrenal Pharm: Pasireotide is a somatostatin analog used to inhibit ACTH and cortisol secretion. It acts by increasing somatostatin. It is a long acting drug that is excreted by the biliary system. What are its side effects? Contraindications?

Answer 338

1. Side effects - -Hyperglycemia - -CV (bradycardia) 2. Cx - -diabetes - -CV problems

Question 339

Adrenal pharm: Drugs for hyperaldosteronism include: 1. Aldosterone antagonists 2. Triamterene and amiloride Aldosterone antagonists include steroidal K+ sparing diuretics (spironolactone and eplerenone). These drugs block _________ receptors leading to dec. expression of Na2+ channels and dec. Na2+ in the plasma.

Answer 339

block aldosterone receptors

Question 340

Adrenal pharm - Hyperaldosteronism can be treated with alodsterone antagonists: 1. Steroidal K+ sparing diuretics (spironolactone, eplerenone) 2. non-steroidal K+ sparing diuretics (Triamterene and amiloride) Triamterene and amiloride are non-steroidal K+ sparing diuretics that act by blocking ______, leading to decreased Na2+ in the plasma

Answer 340

Block Na2+ channels

Question 341

Adrenal pharm - Hyperaldosteronism: steroidal and non-steroidal K+ sparing diuretics have a short (1 day) duration of action (shorter in triamterene). They undergo extensive liver metabolism (except amiloride). Spironolactone begins as a pro-drug that is converted to its active metabolite _____.

Answer 341

- Canrenone (active) | - Canrenooate (inactive)

Question 342

Adrenal pharm - Hyperaldosteronism: Side effects of steroidal and non-steroidal K+ sparing drugs include: 1. Hyperkalemia 2. Metabolic acidosis 3. Gynecomastia, Impotence, Menstural dysfunction (specifically spironolactone) What are drug interactions and contraindications of these drugs?

Answer 342

1. Drug interactions - --HTN drugs (inc. side effects) 2. Cx - -Hyperkalemia - -Pregnancy (steroidal diuretics)

Question 343

Adrenal pharm - Androgen antagonists: Treatment for Hyperandrogenism is based on gender: 1. Females w/ polycystic ovarian syndrome are treated with _______ which is 1st line treatment. 2. Males with hyperandrogenism are treated with _______

Answer 343

1. Estrogen-progesterone (contraceptive pills) 2. Enzalutamide and apalutamide (Androgen receptor antagonists) MOA: inhibit androgen binding to androgen receptor (inhibit nuclear translocation and DNA binding)

Question 344

Adrenal. pharm - Androgen antagonists: ________ has the longest duration (~8d). These drugs need several weeks to reach a steady state.

Answer 344

Enzalutamide

Question 345

Adrenal. pharm - Androgen antagonists include E2/P, enzalutamide and apalutamide. List the side effects, drug interactions and contraindications of androgen antagonists

Answer 345

1. Side effects - -HTN 2. Drug interactions - -strong CYP inducers 3. Cx - -HTN - -pregnancy

Question 346

Adrenal pharm: Addison's disease presents typically with bronze pigmentation of the skin, hypoglycemia, changes in body hair distribution, postural hypotension, weight loss of weakness. How is it treated?

Answer 346

1. Glucocorticoid replacement - --prednisone - -hydrocortisone - -dexamethasone 2. Mineralcorticoid replacement - -fludrocortisone - -aldosterone (poorly absorbed in GI; not used)

Question 347

Adrenal pharm: Drugs for congenital adrenal hyperplasia include: 1. Glucocorticoid replacement therapy 2. Mineralcorticoid replacement therapy 3. Anti-androgenic drugs ___1___ is a glucocorticoid that can be given to neonates and children. It is useful in preventing cortisol crisis. ___2___ and __2___ can be given to adults.

Answer 347

1. Hydrocortisone 2. Dexamethasone and Prednisone NOTE: 95% of cases due to 21 hydroxylase deficiency

Question 348

Adrenal pharm: Drugs for congenital adrenal hyperplasia include: 1. Glucocorticoid replacement therapy 2. Mineralcorticoid replacement therapy 3. Anti-androgenic drugs ______ may be used for mineralcorticoid replacement if necessary

Answer 348

Fludrocortisone

Question 349

Adrenal pharm: Drugs for congenital adrenal hyperplasia include: 1. Glucocorticoid replacement therapy 2. Mineralcorticoid replacement therapy 3. Anti-androgenic drugs True/False - Anti-androgenic drugs include Finasteride, Spironolactone, and enzalutamide/apalutamide. These decrease virilization in women.

Answer 349

True *finasteride, enzalutamide, spironolactone = anti-androgenics

Question 350

Adrenal Pharm: Treatment for males with hypOgonadism include: 1. Testosterone esters (oral tesosterone undecanoate) 2. Nandrolone True/False - These drugs stimulate puberty and secondary sex characteristics in boys. They help improve libido, muscle tone, and bone density in men.

Answer 350

True * DON'T improve sperm production or fertility * Do not cure congenital conditions

Question 351

Adrenal pharm: Treatment for females with hypOgonadism includes 1. Estrogens 2. Growth Hormone True/False - Estrogens (contraceptives or estradiol) can be used to induce puberty in girls and to maintain sexual functioning in women. Growth hormone is used to inc. height.

Answer 351

True *don't cure congenital conditions

Question 352

Adrenal pharm: Testosterone undecanoate (TU) is carried by lipoproteins to lymph vessels where it gets absorbed and subsequently converted to testosterone by esterases. Testosterone is converted to active DHT. As far as long term use of these drugs: 1. esters < non-esters 2. nandrolone < testosterone esters What are contraindications for use?

Answer 352

Prostate and Breast Cancer

Question 353

Adrenal pharm: Drugs for Secondary Hypogonadism include: 1. Clomphene citrate 2. Human chorionic gonadotropin (hCG) ______ is approved for women as it improves ovulation. It may be used off label in men (improves testosterone secretion, sperm production and fertility).

Answer 353

Clomiphene citrate *can also be used in primary hypogonadism

Question 354

Adrenal pharm: True/False - Human chorionic gonadotropin can be used in the treatment of secondary hypogonadism (and primary). It improves testosterone secretion, sperm production and fertility in men and increases progesterone secretion and ovulation in women. In boys it promotes testicular descent.

Answer 354

True

Question 355

Adrenal Pharm: 1. Clomiphene is a non-steroidal selective _____ receptor inhibitor 2. hCG is a hormone produced by the placenta that mimics _________

Answer 355

1. estrogen receptor inhibitor | 2. mimics luteinizing hormone (LH)

Question 356

Adrenal pharm: Clomiphene undergoes enterohepatic re-circulation. Onset is normally greater than 5 days. What are side effects? Contraindications?

Answer 356

1. Side effects - -dec. estrogen activity (hot flashes, vaginal dryness) - -inc. androgens (water retention, gynecomastia) 2. Cx - -pregnancy - -abnormal vaginal bleeding - -Hepatic dysfunction

Question 357

Adrenal pharm: hCG undergoes renal metabolism. It can be combined with testosterone esters to help maintain fertility. Adverse effects include gynecomastia and water retention. What are contraindications?

Answer 357

Pregnancy, Prostate cancer, Renal dysfunction

Question 358

Adrenal pharm: Natural glucocorticoids are cortisol and corticosterone. Synthetic glucocorticoids can be divided based on their duration of action: 1. Short acting (8-12 hrs) 2. Intermediate acting (18-36 hours) 3. Long acting (24-72 hours) List the drugs associated with each

Answer 358

1. Short acting (8-12 hrs) - -hydrocortisone (cortisol), cortisone 2. Intermediate acting (18-36 hours) - -prednisone, prednisolone 3. Long acting (24-72 hours) - -betamethasone - -dexamethasone *take med in morning when first wake = mimic cortisol

Question 359

Adrenal pharm: The DNA binding domain of glucocorticoids and mineralcorticoid receptors is 96% similar. Mineralcorticoid target cells contain a unique enzyme _____, which protects mineralcorticoid receptors by rapidly inactivating glucocorticoids that bind.

Answer 359

11-B hydreoxysteroid dehydrogenase *convert cortisol to cortisone

Question 360

Adrenal pharm: 1. _____ is classified as a mineralcorticoid (salt-retaining). The rest of the drugs are glucocorticoids 2. _____ has equivalent actions at both receptors. Given PO. parenteral, topically. 3. _____ is given PO. It is intermediate acting and is mostly glucocorticoid (anti-inflammatory).

Answer 360

1. Fludrocortisone 2. Cortisone 3. Prednisone

Question 361

Adrenal pharm: Pharmacologic actions of glucocorticoids include: 1. Metabolic and Catabolic (protein catabolism -- gluconeogenesis) 2. Anti-inflammatory 3. Immunosuppressive These meds are mainly used for inflammation (e.g. asthma, IBD) and immunosuppression (e.g. RA, organ transplant). What are common EARLY adverse effects?

Answer 361

1. Common - -weight gain (new fat, new sugar for energy) - -altered mood - -hyperglycemia (profound) - -transient adrenal suppression 2. Sporadic - -anaphylaxis - -acute pancreatitis - -peptic ulcers *Remember: Cortisol is a BIG FIB

Question 362

Adrenal pharm: Pharmacologic actions of glucocorticoids include: 1. Metabolic and Catabolic (protein catabolism -- gluconeogenesis) 2. Anti-inflammatory 3. Immunosuppressive These meds are mainly used for inflammation (e.g. asthma, IBD) and immunosuppression (e.g. RA, organ transplant). What are LATE adverse effects?

Answer 362

1. Common - -central obesity - -cutaneous fragility - -myopathy - -osteoporosis - -growth failure - -prolonged adrenal suppression 2. Sporadic - -glaucoma - -cataracts - -HTN - -opportunistic infections

Question 363

Adrenal pharm: Long term therapy with glucocorticoids can lead to complete adrenal gland suppression and atrophy. True/False - It is imperative to taper these drugs and to avoid abrupt discontinuation to enable time for the adrenal gland to gain adequate function.

Answer 363

True

Question 364

Adrenal pharm: 1. Hypophysectomy causes cortical _____ 2. Stress leading to ACTH leads to _____

Answer 364

1. atrophy | 2. hypertrophy

Question 365

Adrenal pharm: What are the advantages for using Alternate-Day Therapy of glucocorticoids? a. anti-inflammatory effects persist long term b. minimizes HPA suppression c. facilitates HPA recovery d. minimal reduction in bone growth

Answer 365

all of the above *minimal risk for hypercortisolism (Cushing)

Question 366

Adrenal pharm: What are the disadvantages for using Alternate-Day Therapy of glucocorticoids?

Answer 366

1. some patients don't respond | 2. abrupt switch from daily -- alternating days = hypercortisolism (tired, N/V, hypotension) on non-dosing days

Question 367

Adrenal Pharm: While treatment of Adrenal Insufficiency (Addison's disease; hypofunctional state) involves exogenous glucocorticoids and mineralcorticoids, treatment of Hyperfunctional states such as Cushing's involves use of: 1. Surgery (1st line) 2. Adrenolytics 3. Glucocorticoid synthesis inhibitors 4. glucocorticoid receptor blockers List examples of each

Answer 367

2. Adrenolytics - -Mitotane 3. Glucocorticoid Synthesis Inhibitors - --Metyrapone - -Ketoconazole 4. Glucocorticod-R blockers - -Mifepristone NOTE: Cushing disease - endogenous; adenoma; Cushing syndrome - most often due to drug

Question 368

Adrenal pharm: True/False -Mitotane is an adrenolytic that acts by inhibiting 11-hydroxylation of 11-desoxycotrisol and 11-desoxycorticosterone within the adrenal cortex. Net result is inhibition of cortisol and corticosterone synthesis

Answer 368

True Adverse: - -CNS disturbance (lethargy, somnolence) - -up to 80% either GI (nausea, diarrhea) or CNS issues **weeks to months to work

Question 369

Adrenal pharm: True/False - Mitotane structurally resembles DDT (cytotoxic) and thus can cause cellular degeneration and cortical atrophy. ZG cells are minimally affected (acutely) but can be damaged during long-term therapy.

Answer 369

True

Question 370

Adrenal pharm: True/False - Ketoconazole and Fluconazole are anti-fungals that act as glucocorticoid synthesis inhibitors. They are able to inhibit steroidogenesis at large doses. Their anti-androgenic activity is due to inhibition of multiple CYP enzymes and 11B and 17a hydroxylase.

Answer 370

True MOAs: 1. P450-17 alpha 2. P450 11B 3. P450-scc (rate limiting step of all steroids)

Question 371

Adrenal Pharm: Ketoconazole and Fluconazole can take weeks to months to exert effects. They can also act as CYP 3A4 inhibitors. What are adverse effects of these drugs?

Answer 371

- dermatologic rxns - inc. hepatic transaminases - hepatotoxicity Cx: hepatic disease *reversible elevation in LFT's

Question 372

Adrenal pharm: ______ is a glucocorticoid synthesis inhibitor that acts by inhibiting 11b-hydroxylase (converts deoxycortisol to cortisol). It also causes compensatory shunting to androgen production.

Answer 372

Metyrapone *blocks aldosterone (accumulation of precursors -- weak mineralcorticoid activity)

Question 373

Adrenal Pharm: Because Metyrapone causes compensatory shunting to androgen production, patients may experience androgenic effects including Hirsutism and Acne. What are other adverse effects? a. inc. blood pressure b. electrolyte abnormalities c. dizziness, vertigo d. allergic rash

Answer 373

all of the above *b.p, electrolytes - mineralcorticoid effects NOTE: CYP3A4 inducer

Question 374

Adrenal pharm: Mifepristone is a progesterone and glucocorticoid-R antagonist (at high doses). It blocks receptors and interferes with regulation of the HPA axis (inc. ACTH and cortisol). When should it be avoided? What are adverse effects?

Answer 374

Mifepristone * AVOID in severe hepatic impairment * hypOkalemia, endometrial hyperplasia, peripheral edema, arthralgia

Question 375

Adrenal pharm: True/False - Mifepristone is an abortifacient (aborts fetuses) and is used in chemical abortions. It is renally and hepatically dosed.

Answer 375

True

Question 376

Adrenal pharm: _____ is a mineralcorticoid drug that mimics aldosterone action (Na and H2O retention; K+ excretion). It is degraded in the liver and secreted as water-soluble conjugate.

Answer 376

Fludrocortisone * injectable, PO, topical * 1/2 life: 20-30 min MOA: mimics aldosterone

Question 377

Adrenal Pharm: Hyperaldosteronism is treated via aldosterone receptor antagonists. These are 1. Spironolactone 2. Eplerenone These are non-selective aldosterone antagonists that compete with aldosterone for binding at the receptor. What are adverse effects of these drugs?

Answer 377

* *gynecomastia (eplerenone < Spiro) - menstrual irregularity - CNS - lethargy, drowsiness - hypotension - hypErkalemia NOTE: Renally dosed NOTE 2: off label for hirsutisim, acne vulgaris, hormone replacement for M to F gender change

Question 378

Adrenal pharm: Pheochromocytoma is a tumor of the chromaffin cells that results in secretion of high levels of catecholamines (mainly NE). This results in activation of a-adrenergic recptors and inc. b.p. Treatment includes: 1. Surgery (primary option) 2. Alpha-adrenergic antagonists 3. B-blockers Alpha adrenergic antagonists are used as pre-treatment pharmacotherapy (usually 10-14 days prior to surgery). They require daily blood pressure monitoring and high Na diet (by 2nd/3rd day). What is the typical agent used?

Answer 378

1. Non-selective = Typical - -Phenoxybenzamine *** 2. Long term blockade with selective agents - -prazosin, terazosin, doxasozine 3. Peri-operative therapy: - -IV phentolamine

Question 379

Adrenal pharm: Pheochromocytoma is a tumor of the chromaffin cells that results in secretion of high levels of catecholamines (mainly NE). This results in activation of a-adrenergic recptors and inc. b.p. Treatment includes: 1. Surgery (primary option) 2. Alpha-adrenergic antagonists 3. B-blockers B-blockers should NEVER be administered until after adequate alpha blockade has been established (2-3 days-ish) because unopposed alpha blockade could lead to HTN crisis. What is the typical agent?

Answer 379

Labetalol (or Carvedilol) * Non-selective, mixed a1/B1/B2 blockade * use if significant tachycardia occurs after adrenergic blockade * NEVER administer until a-blockade established (avoid HTN crisis -- unopposed alpha stimulation)

Question 380

Adrenal pharm: Unopposed alpha stimulation is defined as acute inc. in blood pressure (HTN crisis) or worsening coronary artery vasoconstriction after B-blockade is administered. True/False -A balance between alpha 1 and B2 stimulatin results in regulation of vascular tone. However, if a cardioselective, pure B1/B2 blocker (propanolol) is used, balance is disrupted in favor of alpha 1 and vasoconstriction is favored.

Answer 380

True a1 - vasoconstriction B1 - HR, contractility B2 - SM relaxation *see wrap up slide 58

Question 381

Review Wallace Pharm Packet 1. PRL drugs 2. GH drugs 3. Vasopressin 4. Oxytocin 5. Tests - -TSH, Dexamethasone, Metyrapone, Cosyntropin, glucose tolerance, TRH, Insulin

Answer 381

Review the packet *adverse effects, Cx, Interactions **