Flashcards in SA Endocrine Deck (151)
Briefy describe the hypothalamus-pituitary-thyroid axis
Hypothalamus releases TRH (thyroid releasing hormone)
-> Pituitary gland releases TSH (thyroid stimulating hormone)
-> Thyroid gland releases T4 and T3
-> These have a negative feedback effect on the pituitary gland and hypothalamus
Of T3 and T4, which is more numerous in peripheral tissues?
Which is more potent, T3 or T4?
How are thyroid hormones bound in the blood?
To plasma proteins
Only unbound thyroid hormones are active
What are the functions of the thyroid hormones?
-Increase metabolic rate and 02 consumption of most tissues
-Positive inotropic and chronotropic effects on heart (increase HR and contractility)
-Cause hypertension (increase number and affinity of beta-adrenergic receptors)
-Metabolic effects of muscle and adipose tissue (weight loss)
-Stimulate erythropoiesis and regulate cholesterol synthesis and degradation
Which kinds of dogs are affected by hypothyroidism?
Middle aged to older
What are the 2 main forms of hypothyroidism in dogs?
Congenital and acquired (may be primary or secondary)
How may canine hypothyroidism occur?
-Result of thyroid hypoplasia/aplasia/dyshormonogenesis (thyroid anatomically normal but can't synthesise normal thyroid hormones)
-Autosomal recessive in Fox and Rat terriers
-Panhypopituitarism in GSD (deficiency in all pituitary hormones)
Give some primary causes of acquired hypothyroidism in dogs
-Lymphocytic thyroiditis and/or idiopathic atrophy
-Aggressive thyroid neoplasia and treatment with potentiated sulphonamides
Give some clinical signs of canine hypothyroidism
-Obesity with a normal appetite
-Cold intolerance (always looking for warmth)
-Hair thinning/alopecia (oily trunk and tail)
What would you see on a haematology of a dog with hypothyroidism?
Mild normocytic, normochromic, non-regenerative anaemia (32-44% of cases)
What would you see on a biochemistry of a dog with hypothyroidism?
-Mild elevations in creatinine kinase, ALP and ALT
-Elevation of circulating fructosamine
How can you measure thyroid hormones?
-Total T4 (tT4)
-Free T4 (fT4)
-Total T3 (tT3)
Why may you get false positive results when doing a total T4 test to diagnose canine hypothyroidism?
Total T4 can be reduced by non-thyroid illness and drug therapy (eg sulphonamides)
Which dog breeds have lower-than-normal values for total T4?
Greyhounds and other sighthounds and sled dogs
What is the best way to diagnose canine hypothryoidism?
TSH combined with tT4
(Will have low tT4 and high TSH due to lack of negative feedback)
How do you treat canine hypothyroidism?
-Start at 0.01-.02mg/kg q 12hrs (lower dose for cardiac patients)
-Metabolic signs should resolve in a few weeks, but dermatological changes may take months to resolve
What are the only 3 instances that a dog may develop hyperthyroidism?
-Over-supplementation in hypothyroid dogs
-Neoplasia affecting thyroid gland
-Raw food diet containing neck meat and thyroid tissue (not in UK)
Which cat breed is predisposed to diabetes?
Which kinds of cats are more affected by hyperthyroidism?
-Older cats 13-14 years old
-(Himalayan and Siamese are less at risk)
How does feline hyperthyroidism typically occur?
-Nodular adenomatous hyperplasia of thyroid gland (usually both lobes)
-Occasionally due to functional malignant tumours (1-3% of cases)
Give the clincial signs of feline hyperthyroidism
-Weight loss with increased appetite
-Hyperactivity/behaviour change eg nervous/aggressive
-GI signs (vomiting/diarrhoea)
-Tachycardia, heart murmur, cardiac failure
-Skin and hair coat changes
What is a 'thyroid storm'?
-Stress eg vets -> increased hypertension -> tachycardia (due to excess T4) -> could have sudden death
What may you see on a haematology and biochemistry of a cat with hyperthyroidism?
-Mild to moderate erythrocytosis and macrocytosis
-Increased Heinz bodies
-Increased mean platelet size
-Increased ALP, ALT, AST, LDH
What may you see on a urinalysis of a cat with hyperthyroidism?
May see low SG due to polyuria (+/- renal failure)
How do you usually diagnose feline hyperthyroidism?
Clincial signs and tT4
How else could you diagnose feline hyperthyroidism?
-T3 suppression tests (for borderline/early cases)
-Radionucleotide uptake and imaging (scintigraphy; differentiates between bilateral and unilateral disease)
-Both rarely used
What are the main treatment options for feline hyperthyroidism?
How can you medically manage hyperthyroidism in cats?
-Thiamazole (previously called methimazole; Felimazole): 2.5mg/cat q 12 hrs initially, or available in cream form- ear pinnae
-Carimazole (Vidalta; metabolised to thiamazole): 15mg once daily (as less bioavailable)
How often should you measure tT4 after starting medical tx for feline hyperthyroidism?
After 2 weeks then, once stable, every 3 months
Why may you give beta blockers to a cat with hyperthyroidism?
-Used to stabilise cats prior to surgery
-Decrease the neuromuscular and cardiovascular effects of hyperthyroidism (eg hyperexcitablity, hypertension, cardiac hypertrophy)
-Don't use in cats with congestive heart failure or asthma
Why may you give potassium iodate to a cat with hyperthyroidism?
-Used to stabilise cats prior to surgery
-Source of stable iodine, which may temporarily decrease the rate of thyroid hormone systhesis
Give some pros and cons of surgical removal of the thyroid gland to tx feline hyperthyroidism
-Greater anaesthetic risks due to CV, hepatic and GI dysfunction
-Possible complications eg larygneal paralysis, Horners, hypocalcaemia, recurrence of hyperthyroidism
Give some pros of radioactive iodine treatment to treat feline hyperthyroidism
-Only targets affected thyroid tissue
-Treats any hyperfunctioning ectopic tissue
Give some cons of radioactive iodine treatment to treat feline hyperthyroidism
-Cat must be isolated for up to 3 weeks as will be radioactive (as are faeces-need proper disposal)
Give some side effects of medical treatment of feline hyperthyroidism
-Anorexia, vomiting, lethargy
-Bleeding diatheses (epistaxis and oral bleeding)
-Hepatopathy, may have icterus
-Eosinophilia, lymphocytosis, leukopenia
Why may azotaemia become evident after medical management of feline hyperthyroidism has begun?
-Hyperthryoidism increases GFR, so may have been masking underlying renal failure
What are the 4 surgical techniques for thyroid removal?
Describe an extracapsular thyroidectomy
-Ligate cranial and caudal thyroid arteries
-Intact thyroid is removed with its capsule with no attempt to preserve the external parathyroid gland
-High rate of post-op hypocalcaemia
Describe an intracapsular thyroidectomy
-Incise thyroid capsule
-Bluntly dissect thyroid gland from capsule
-Capsule left in situ to preserve the cranial parathyroid gland
Describe a modified extracapsular thyroidectomy
-Incise the thyroid capsule around the cranial parathyroid gland and separate it from the thyroid gland
-The parathyroid branch of the cranial thyroid artery is preserved
-Remove remaining thyroid gland with capsule, leaving an intact cranial parathyroid gland
Describe a modified intracapsular thyroidectomy
-Incise the ventral capsule of thyroid gland
-Bluntly dissect away the thyroid parenchyma from the capsule
-Cranial PT gland and blood vessels are preserved
-Most of the capsule is removed apart from a small cuff surrounding the parathyroid gland
Which technique is recommended for surgical thyroidectomy?
Either modified intracapsular or modified extracapsular
What should you do if you accidentally damage the blood supply to the parathyroid gland when removing the thyroid gland?
Transplantation of parathyroid gland:
-Cut into 1mm cubes
-Insert into sternohyoideus/thyroideus
-Should be functional within 1-3 weeks
Why may hypocalcaemia occur after thyroid gland removal?
-Damage to parathyroid blood supply, or inadvertent parathyroidectomy
What is secreted by functional adrenal adenomas and carcinomas?
What is secreted by a phaeochromocytoma?
Catecholamines eg adrenaline
Give some complications of adrenalectomy
-Haemorrhage (very vascular)
-Surges of catecholamine release when handling phaeochromocytomas -> hypertension, vetricular tachycardia, arrhythmias
Cortisol is produced where? Under the control of what?
Adrenal glands (zona fasiculata) under the control of ACTH
Give some functions of cortisol
Homeostasis during stress:
-Delayed wound healing
-Catabolism (fat and protein deradation)
-Inhibition of DNA/protein synthesis
What is the key function of aldosterone?
Retention of sodium and excretion of potassium by the kidney
What kinds of dogs are affected by hyperadrenocortism (cushings)?
Middle aged to older dogs
Give some common clinical signs of hyperadrenoacorticism (Cushings)
-Abdominal distension (pot belly)
-Bruising, coat changes
What haem and biochem results would you see in a dog with hyperadrenocorticism (Cushings)?
-Increased ALKP and ALT
What may you see on a urinalysis in a dog with hyperadrenocorticism (Cushings)?
-Low specific gravity (<1.018-1.020)
What is the difference between pituitary-dependent and adrenal-dependent hyperadrenocorticism?
-Pituitary-dependent: excessive secretion of ACTH by a pituitary tumour -> adrenal hyperplasia -> increased cortisol secretion
-Adrenal-dependent: caused by an adrenal tumour which secretes excessive amounts of cortisol
What is the cause of iatrogenic hyperadrenocorticism?
Excessive glucocorticoid administration
Which dog breeds are predisposed to hyperadrenocorticism (cushings)?
Labradors, poodles, beagles, daschunds, terriers
How do you test for hyperadrenocorticism (cushings)?
-ACTH stimulation test
-Low-dose dexamethasone suppression test
-Urine cortisol creatinine ratio (good for proving animal does not have cushings)
Describe the ACTH stimulation test
-Give 5ug/kg ACTH
-Measure cortisol levels at 0 and 1 hours
-Avoid feeding during test
-A normal healthy animal should have post ACTH concentrations that are 2-3 times higher than the basal values of cortisol
-An affected, hypertrophied gland will produce even more cortisol
Describe the low dose dexamethasone suppression test
-0.01mg/kg dexamethasone iv
-Blood sample at 0, 3 and 8 hours
-Avoid feeding during test
-A healthy animal will suppress cortisol to <50% of the basal level after 3 hours and to <40 nmol/l after 8 hours
-An animal with adrenal dependent HAC will fail to suppress at 3 and 8 hours
-An animal with pituitary dependent HAC will suppress at 3 hours and escape suppression at 8 hours.
How would the adrenals appear on an US if affected by adrenal-dependent and pituitary-dependent hyperadrenocorticism?
Adrenal-dependent: one adrenal bigger than the other
Pituitary-dependent: both glands are stimulated so both are big
What is the most effective test for diagnosing hyperadrenocorticism?
Low dose dexamethasone suppression test
How do you treat hyperadrenocorticism (cushings)?
-Trilostane (inhibits glucocorticoid synthesis)
-Starting dose= 2.5mg/kg sid
Which test allows you to differentiate between adrenal- and pituitary-dependent hyperadrenocorticism?
Low dose dexamethasone suppression test
-A healthy animal will suppress cortisol to <50% of the
basal level after 3 hours and to <40 nmol/l after 8 hours
-An animal with adrenal dependent HAC will fail to
suppress at 3 and 8 hours
-An animal with pituitary dependent HAC will suppress at 3 hours and escape suppression at 8 hours
Can also do ACTH assay: normal= 20-100pg/ml, PDH= >45, ADH= <20
Give some side effects of Trilostane (tx for hyperadrenocorticism)
-Lack of efficacy
-Vomiting and diarrhoea
How should you monitor hyperadrenocorticism (cushings) once medical treatment has started?
Do ACTH stimulation tests every 3 months for the first year then every 6 months
Give a clinical sign of a pituitary macroadenoma
What causes primary hypoadrenocorticism (Addisons)?
Destruction of >90% of adrenal cortex -> reduced glucocorticoid secretion
What causes secondary hypoadrenocorticism (Addisons)?
Deficiency in ACTH secretion by the pituitary gland (eg trauma, tumour) -> atrophy of adrenal cortex-> reduced glucocorticoid secretion`
Which dog breeds are predisposed to hypoadrenocorticism (Addisons)?
Standard Poodle, Beardies, Great Dane, Portugese Water Dog, WHWT, St Bernard, Wheaten Terrier, Rottweiler, Leonberger
Which kinds of dogs are more affected by hypoadrenocorticism (Addisons)?
Middle aged females
Give some clinical signs of hypoadrenocorticism (Addisons)
-Vomiting (+/- blood) and diarrhoea/melaena
What would you find on a physical examination of a dog with hypoadrenocorticism (Addisons)?
-Increased CRT (sign of poor perfusion)
What might you find on a haem and biochem of a dog with hypoadrenocorticism (Addisons)?
-Mild non-regenerative anaemia
-Lymphpcytosis +/- eosinophilia
-Na:K <27:1 (high potassium, low sodium)
-Isosthenuric to hypersthenuric urine
How do you treat acute hypoadrenocorticism (Addisonian crisis)?
-IV fluids (0.9% NaCl) to correct hypovolaemia (3-4x maintenance)
-Glucose can be added to cause insulin release and reduce hyperkalaemia
-ACTH stimulation test
-Dexamethasone sodium phosphate 0.1-0.2mg/kg iv q 24hrs
-Or constant infusion of hydrocortisone at a rate of 0.625mg/kg/h
-Once eating: oral prednisolone (can usually be discontinued once animal is stable) and fludrocortisone q 24hrs. DOCP q 25 days
Give some adverse outcomes of treatment for hypoadrenocorticism (Addisons)
-Acute renal failure
-Myelinosis (depression, weakness, ataxia, tetraparesis)
What is a phaechromocytoma?
Tumour of the adrenal medulla secreting catecholamines (eg adrenaline)
Give some clinical signs of a phaeochromocytoma
Signs usually episodic:
-Hypertension (retinal detachment)
How do you diagnose a phaeochromocytoma?
Radiography or US
How do you treat a phaeochromocytoma?
Radical excision of adrenal gland, antihypertensive medication
What causes hyperaldosteronism?
Adrenal tumour producing aldsterone
Give some clinical signs of hyperaldosteronism
-Neck ventroflexion (hypokalaemia)
-Hypertension (sodium retention -> water retention -> increases BP)
How do you treat hyperaldosteronism?
-Restrict sodium and supplement potassium
-Spironolactone (aldosterone antagonist)
Give the 5 major differential diagnoses for PUPD
-Iatrogenic (eg glucocorticoids)
-Renal medullary washout
-Primary polydipsia (problem of thirst centre in brain)
What tests should you run when investigating PUPD?
-Haem and biochem
-Bile acids (liver disease?)
When should you do a water deprivation test?
What does it allow you to differentiate?
-After all other dynamic testing (eg bloods, bile acids, T4, urinalysis, HAC has been ruled out)
-Allows you to differentiate central diabetes insipidus, primary nephrogenic diabetes insipidus, and primary PD
What is DDAVP?
What is the recommended starting dose for insulin in diabetic dogs?
What about cats?
-Start with an intermediate insulin at a dose of 0.25-0.5 units/kg BID
-1 to 2 units BID for cats
Give some endocrine causes of poor growth
-Pituitary dwarfism (rare)
Pituitary dwarfism affects primarily which breed of dog?
How does pituitary dwarfism occur?
-Rare congenital lesion (developmental defect in pituitary gland)
-Failure of GH secretion
-May be combined with deficiencies in FSH, LS, TSH
Give some features of pituitary dwarfism
-Failure to develop adult coat
-Delayed dental eruption
-Delayed dental eruption
-Delayed growth plate closure
-Thin, fragile, hyperpigmented skin
How can you treat pituitary dwarfism?
-Progestagens (induces GH secretion from mammary tissue)
-GH (results usually disappointing)
What is acromegally?
When does acromegally occur in dogs and cats?
-Cats: pituitary tumour in older males (often diabetic)
-Dogs: mammary tissue in response to progestagens/progesterone in intact females (luteal phase) or females receiving progestagens
Describe the pathogenesis of acromegally
Chronic excess GH -> insulin antagonism -> diabetes mellitus
-> also anabolic effects on organs, bone, cartilage
Give some clinical features of acromegally
-Insulin-resistant diabetes mellitus
-Excessive growth of extremities
-Prognathism, wide interdental spaces
-Soft tissue proliferation
How would you diagnose acromegally?
-Clinical signs inc diabetes mellitus
-Increased liver enzymes
How would you treat acromegally?
Bitch: spay/stop progestagens. Bony changes are irreversible
Cat: control diabetes mellitus. Surgery (hypophysectomy-pituitary gland removal). Radiation of pituitary mass
What are the functions of PTH?
-Reabsorption of calcium and phosphate from bone
-Stimulates absorption of calcium and phosphate from gut via synthesis of calcitriol
-Increased urinary excretion of PO4 and retention of Ca2+
-Overall effects= increase blood Ca2+ and decrease blood PO4
What causes primary hyperpararthyroidism?
-Excess of PTH
-Most cases are due to a functional adenoma (rarely carcinoma)
-Results in hypercalcamia
Give some clinical signs of hypercalcaemia
-Muscle weakness, lethargy, anorexia, vomiting, gut stasis
-Calcium oxalate crystals may cause cystitis
-Acute renal failure
How do you treat hyperparathyroidism?
Restore normal calcium level:
-Fluids (0.9% NaCl)
Surgical removal of parathyroid tumour once stabilised
What causes secondary hyperparathyroidism?
-Nutritional secondary hyperpaathyroidism (rare; unbalanced homemade diets)
-Renal secondary hyperpaathyroidism (rubber jaw; secondary to chronic renal failure)
What is pseudo-hyperparathyroidism?
Caused by a PTH-like protein secreted by malignant apocrine tumours eg anal sac tumours, multiple myelomas, lymphomas
What causes hypoparathyroidism?
-Lack of PTH: can be primary or secondary
-Primary: immune-mediated destruction of parathyroid glands
-Secondary: damage to glands by thyroid surgery (cats), local disease etc
-Results in hypocalcaemia and hyperphosphataemia
Give some clinical signs of hypocalcaemia
-Muscle twitching, spasm, tetany
-Tachycardia, weak pulses
How do you treat hypocalcaemia?
-Emergency: iv fluids, iv calcium borogluconate
-Maintenance: oral calcium, oral vitamin D
Give some factors that cause diabetes in dogs
Loss of islets:
-Hormonal/drug antagonism (eg long-term steroids)
Give some factors that cause diabetes in cats
Insulin resistance +/- relative insuin deficiency caused by:
-GH (may also have acromegaly)
Give the functons of insulin
-Stimulates uptake of glucose by muscles and other cells
Give some clinical signs of diabetes mellitus
-White cataract formation in dogs (rare in cats)
How do you diagnose diabetes mellitus?
-History (eg sudden onset PUPD)
-Urinalysis (low SG, glycosuria, ketonuria, active sediment)
-Glycosylated Hb and fructosamine
-Persistent fasting hyperglycemia (fasting blood
glucose greater than 11mmol/l)
How do you treat diabetes mellitus?
-Lifelong in dogs: insulin, diet, routine
-Cats: insulin; may go in and out of remission
What are the 3 types of insulin?
-Short-acting (regular or crystalline; primarily used for ketoacidosis)
-Long-acting (eg Ultralente)
How often should you give insulin to diabetic dogs?
-Twice daily with food
-Starting dose: 0.25-0.5iu/kg
What kind of diet would you recommend to a diabetic dog?
A diet low in fat and high in fibe
How often should you give insulin to diabetic cats?
-Caninulin (intermiediate-acting) or Prozinc (long-acting)
What kind of diet would you recommend to a diabetic cat?
High protein/low carbohydrate diet
What are oral hypoglycaemic agents?
-Alternative to insulin therapy
-Sulfonylureas (cause stimulation of insulin release and increase insulin sensitivity. Require some residual beta cell function so are only suitable in cats, not dogs)
How should you treat a diabetic pet experiencing a hypoglycaemic episode?
-Give a sugary substance under the tongue
-Avoid insulin dose if imminent
What should you do if a diabetic pet is not eating?
Reduce insulin dose by 50% (don't stop insulin as body will generate its own glucose)
How can you monitor a diabetic pet?
Blood glucose curves (sample every 2 hours)
On a blood glucose curve, when will blood glucose be lowest?
What value should it be?
6-8 hours after insulin is given
Should be between 4.5-9mmol/L
How can you distinguish between diabetes mellitus and stress-induced hyperglycemia in cats?
Test fructosamine (diagnoses diabetes)
Give some chronic complications of diabetes mellitus
What would be your thoughts if you were treating a diabetic pet whose blood glucose wasn't decreasing and it was on an insuin dose of >2iu/kg?
Give some causes of ketoacidosis
-Increasing circulating levels of diabetogenic hormones
Give some negative effects that ketoacidosis has on the body
-Spillage of ketones into urine -> osmotic diuresis -> loss of H2O and electrolytes -> reduced perfusion to kidneys ->azotaemia
Give some clinical signs of ketoacidosis
How do you treat ketoacidosis?
-Provide adequate amounts of insulin (intramuscular insulin therapy/constant low-dose infusion)
-Restore water and electrolyte losses (supplement K+, phohsphate, bicarb, give fluids-isotonic crystalloids with K+ in)
-Correct acidosis (usually happens anyway as you correct other things)
-Identify any concurrent illness
-Provide CHO substrate
What is the target range for blood glucose when treating diabetes mellitus?
What is an insulinoma?
-Functional tumour of pancreatic beta cells -> high insulin levels -> hypoglycaemia
Give some clinical signs of an insulinoma
-Weakness, trembling, ataxia, seizures
+/- other neuro signs
-May have weight gain
How do you diagnose an insulinoma?
-Fast until animal becomes hypoglycaemic
-Measure insulin: normal/high -> insulinoma
-May see a small pancreatic mass on US
-Will also have persistent hypoglycaemia
How do you treat an insulinoma?
-IV glucose if needed
-Avoid excess stimulation of insulin: frequent small meals, diet high in complex carbohydrates and protein
What is a gastrinoma?
-Pancreatic gastrin-producing tumour
-Stimulates parietal cells to produce lots of acid, risk of ulceration
Where are the parathyroid glands located?
2 associated with each thyroid gland:
1 cranial and external
1 internal (caudal half of thyroid)
Give some clinical signs of hypocalcaemia post-operatively after thyroidectomy
Facial/generalised muscle twitching
How do you treat acute hypocalcaemia following thyroidectomy?
10% calcium gluconate iv slowly over 10-20 mins
Once stable: CRI of calcium gluconate at 5-15mg/kg/hr iv
Monitor for bradycardia and arrhythmias
Once stable, give oral vit D and calcium
Most parathyroid nodules in dogs are what?
Is pituitary-dependent hyperadrenocorticism more common in small or large breed dogs?
What about adrenal-dependent?
PDH: small breeds
ADH: large breeds
How do you treat hyperkalaemia seen with hypoadrenocorticism (Addisons)?
Dextrose saline and insulin
How do you treat hypoadrenocorticism (Addisons)?
Dexamethasone sodium phosphate (best)
Give a blood glucose range for a stable diabetic dog
5-12mmol/L over 24 hours
How do you diagnose diabetic ketoacidosis?
Diabetes plus ketonuria
What are the 2 main types of diabetes insipidus?
Central (neurogenic): lack of vasopressin -> reduced water retention
Nephrogenic: primary (ADH deficiency) or secondary (eg renal failure, Cushings, Addisons)
Which hormones does the pituitary gland secrete?