Hypothyroidism - Dogs & Cats

Question 1

______ is a large glycoprotein containing iodotyrosines, precursors of thyroid hormones.

Answer 1

Thyroglobulin (stored in colloid)

Question 2

What hormone(s) does the thyroid gland synthesize and secrete?

Answer 2

thyroxine = T4
triodothyronine = T3

Question 3

T/F: Thyroid hormones are bound to albumin and not globulin.

Answer 3

F - 60% of T4 & T3 are bound to thyroxine binding globulin, 17% to transthyretin, 12% to albumin and 11% to various lipoproteins

Question 4

In health, when thyroid levels are low the hypothalamus secretes _____ to promote the anterior pituitary to release _________.

Answer 4

thyrotropin releasing hormone (TRH)

thyrotropin stimulating hormone (TSH)

Question 5

What are the functions of thyroid hormones? (7)

Answer 5

metabolic rate
growth
nervous system development
tissue turnover
cardiac - inotropic, chronotropic
lipid synthesis & metabolism
erythropoiesis

Question 6

What is the functional unit of the thyroid gland? Describe what is contained intra- and extra-cellularly.

Answer 6

thyroid follicle
intra = colloid, which stores thyroglobulin
extra = thyroid hormone (T3, T4)

Question 7

What is the role of thyroid peroxidase (TPO) in thyroid hormone synthesis?

Answer 7

oxidation of iodide to iodine
facilitates iodine organification = iodination of tyrosyl residues on thyroglobulin

Question 8

What are the 3 categories of hypothyroidism?

Answer 8

primary = thyroid gland
secondary = pituitary gland
tertiary = hypothalamus

**central hypothyroidism may be used to describe secondary or tertiary (distinguishing between the 2 is not always possible)

Question 9

Congenital hypothyroidism is rare. What breed of dogs has central hypothyroidism been reported in?

Answer 9

Schnauzers, giant/mini

Question 10

Congenital hypothyroidism is rare. which breed(s) of dog(s) have dyshormonogenesis and thyroperodisase deficiency been reported in?

Answer 10

frenchies
spanish water dogs
teterfields
toy fox
rat terriers

Question 11

Congenital hypothyroidism is rare. Which breed(s) of dog(s) has congenital hypothyroidism been reported in due to sodium-iodide symporter (NIS) deficiency?

Answer 11

Papillons
Shih Tzus

Question 12

Central hypothyroidism is rare. What is the most common cause of central hypothyroidism?

Answer 12

Pituitary neoplasia
Surgical hypophysectomy

Question 13

What are the most common causes of hypothyroidism in the dog?

Answer 13

lympochytic thyroiditis
idiopathic thyroid atrophy

Question 14

What drugs have been implicated in causing hypothyroidism?

Answer 14

potentiated sulphonamides
toceranib (Palladia)
pred
phenobarbital
clompiramine
carprofen

Question 15

What are the benefits in running a thyroglobulin autoantibody (TgAA) test?

Answer 15

Clinical suspicion of hypothyroidism is HIGH and your T4 is normal/high with high TSH – TgAA can falsely elevate T4 levels on the assay (-J Herm)

TgAA positivity may allow you to screen for breeds that are increased risk for developing hypothyroidism

Question 16

Hypothyroidism - Signalment

Answer 16

Middle to older (mean of 7, range of 0.5-15)
Purebred dogs
Neutered (F>M)

(English setter, gordon setter, golden retrievers, doberman pinschers, old english sheepdogs, rhodesian ridgebacks, cocker spaniels, boxers, giant schnauzers, dobermans, borzoi, beagles, great danes)

Question 17

Hypothyroidism - Clinical Signs

Answer 17

> 80% = lethargy, weight gain, exercise intolerance, mental dullness, cold intolerance, generalized weakness, shivering

40-50% = overweight, obese

80% = endocrine alopecia

Question 18

Describe endocrine alopecia

Answer 18

non-pruritic
bilaterally symmetric
tendency to spare the head and extremities

Question 19

T/F: Pyoderma is a common sequelae of hypothyroidism.

Answer 19

F - <10% of dogs with recurrent pyoderma are diagnosed with hypothyroidism

Question 20

T/F: Hypothyroidism is associated with the development of adult-onset demodicosis.

Answer 20

True

Question 21

artherosclerosis

Answer 21

condition that occurs due to a build up in cholesterol, calcium, other substances

**few reports of aortic thromboembolism and severe atherosclerosis associated with hypothyroidism

Question 22

Proposed mechanisms of hypothyroidism and gallbladder mucoceles.

Answer 22

dyslipidemia
gallbladder dysmotility
altered bile acid composition
decreased bile flow
biliary stasis

Question 23

Clinical features of congenital hypothyroidism.

Answer 23

disproportionally wide skulls
macroglossia (large tongue)
delayed dental eruption
square trunk
short limbs
+/- constipation
mental impairment
+/- goiter

Question 24

CBC findings - Hypothyroidism

Answer 24

Mild NNN anemia (“physiologic anemia”- 50%

Leukocytosis is unusual

Question 25

Why can hypothyroidism cause a, "physiologic anemia"?

Answer 25

1. decreased EPO production 2. Lack of direct stimulatory effect of T3/T4 on bone marrow

Question 26

Serum biochemistry findings - Hypothyroidism

Answer 26

Hypercholesterolemia - 75% (often with hyperTGs) Increased CK - 18-35% Increased fructosamine - 36-82% Mild ALP, GGT elevations - 30% Mildly high creatinine - 30% High SDMA - 50%

Question 27

Why does hypothyroidism result in hypercholesterolemia and hypertriglyceridemia?

Answer 27

T3/T4 stimulates all aspects of lipid metabolism (synthesis, mobilization, degradation) **degradation is severely affected, resulting in lipid accumulation

Question 28

How can sample timing (circadian rhythm), age and sex impact thyroid hormone secretion?

Answer 28

+/- episodic fluctuations TT4, fT4 decline with age cTSH increase with age TT$ can be 2-5x higher in young dogs (<3mo) sex, stage of estrus, season have been variably reported to affect thyroid hormones (clinically insignificant)

Question 29

Which breed of dogs are known to have low circulating TT4?

Answer 29

Sight hounds: Greyhounds - 90% Basenjis - 75% Sloughis - 65% Whippets - 35% Scottish Deerhounds - 5%

Question 30

Which breed of dogs can have low TT3 levels?

Answer 30

Salukies Irish Wolfounds

Question 31

Non-thyroidal illness (NTI) can impact thyroid hormones and thyrotropin (TSH) depending on the severity of illness. Describe what you would expect T3, T4, fT4 and TSH to do with mild illness.

Answer 31

TT3 - mildly decreased TT4 - unchanged fT4 - unchanged TSH - unchanged

Question 32

Non-thyroidal illness (NTI) can impact thyroid hormones and thyrotropin (TSH) depending on the severity of illness. Describe what you would expect T3, T4, fT4 and TSH to do with moderate illness.

Answer 32

TT3 - mod decreased TT4 - mildly decreased fT4 - anything TSH - unchanged/ decreased

Question 33

Non-thyroidal illness (NTI) can impact thyroid hormones and thyrotropin (TSH) depending on the severity of illness. Describe what you would expect T3, T4, fT4 and TSH to do with severe illness.

Answer 33

TT3 - severely decreased TT4 - mod decreased fT4 - unchanged/ decreased TSH - mod decreased

Question 34

Non-thyroidal illness (NTI) can impact thyroid hormones and thyrotropin (TSH) depending on the severity of illness. Describe what you would expect T3, T4, fT4 and TSH to do during the recovery phase.

Answer 34

TT3 - unchanged/decreased TT4 - unchanged/decreased fT4 - unchanged/decreased TSH - unchanged/increased

Question 35

Drug therapy can impact serum concentrations of thyroid hormones and thyrotropin (TSH). Describe what you would expect T3, T4, fT4 and TSH to do with prednisone/prednisolone therapy.

Answer 35

TT4 - unchanged/ decreased fT4 - unchanged/ decreased TSH - unchanged/ decreased

Question 36

Drug therapy can impact serum concentrations of thyroid hormones and thyrotropin (TSH). Describe what you would expect T3, T4, fT4 and TSH to do with phenobarbital therapy.

Answer 36

TT4 - unchanged/ decreased fT4 - unchanged/ decreased TSH - anything* *associated with increased TSH without exceeding upper reference limit

Question 37

Drug therapy can impact serum concentrations of thyroid hormones and thyrotropin (TSH). Describe what you would expect T3, T4, fT4 and TSH to do with sulphonamides therapy.

Answer 37

TT4 - decreased fT4 - decreased TSH - increased

Question 38

Drug therapy can impact serum concentrations of thyroid hormones and thyrotropin (TSH). Describe what you would expect T3, T4, fT4 and TSH to do with toceranib (Palladia) therapy.

Answer 38

TT4 - decreased fT4 - decreased TSH - increased

Question 39

Drug therapy can impact serum concentrations of thyroid hormones and thyrotropin (TSH). Describe what you would expect T3, T4, fT4 and TSH to do with carprofen therapy.

Answer 39

TT4 - unchanged/ decreased fT4 - unchanged/ decreased TSH - unchanged/ decreased

Question 40

Why is TT3 of limited value for diagnosing hypothyroidism?

Answer 40

low diagnostic sensitivity TT3 are WNL or above RIs in 90% of hypothyroid dogs

Question 41

When would you measure TT3 in dogs?

Answer 41

In breeds known to have low TT4, should have normal TT3 = Greyhounds

Question 42

What is the most frequently recommended screening test for hypothyroidism? What can falsely elevate this value?

Answer 42

TT4 T4AA's can falsely increase measured values - 14% of dogs with hypothyroidism

Question 43

What is the most specific/ accurate test in diagnosing hypothyroidism in dogs?

Answer 43

fT4 - equilibrium dialysis, less affected by extrathyroidal factors (vs TT4)

Question 44

The TSH stimulation test was once thought of as the "gold standard" for diagnosing hypothyroidism (product no longer available). What level of TT4 is suggestive of hypothyroidism?

Answer 44

TT4 <1.7 100% sensitive >90% specific

Question 45

Explain why synthetic T3 is not the treatment of choice for canine hypothyroidism?

Answer 45

increased risk of thyrotoxicosis d/t its shorter half life requiring multiple daily doses may result in T4 deficiency within the brain and pituitary gland

Question 46

When is the soonest you can measure thyroid levels after starting thyroid supplementation?

Answer 46

2-weeks = steady state

Question 47

Sequelae of thyroid supplementation - i.e, what should you warn clients about when you start treatment for hypothyroidism?

Answer 47

change in mentation hyperactivity weight loss - 10% expected within first few months of therapy *derm changes can take 2-3 mo, neurologic improvement 6 mo

Question 48

What clincopathology changes do you expect to see when starting treatment for hypothyroidism?

Answer 48

1. improvement in cholesterol and triglycride 2. increase in RBC during first 3mo 3. fructosamine decreases (protein turnover increases) 4. improvement in creatinine, SDMA

Question 49

When monitoring TT4 after starting treatment, what value is usually associated with an inadequate clinical response/ should prompt you to INCREASE the dose?

Answer 49

<2.7 mcg/dL (35 nmol/L)

Question 50

When monitoring TT4 after starting treatment, although dogs are usually resistant to clinical thyrotoxicosis, what values are usually should prompt you to LOWER the dose?

Answer 50

7-7.8 mcg/dL (90-100nmol/L), or greater

Question 51

What is the goal TT4 after initiating treatment for hypothyroidism?

Answer 51

high end/ just above reference interval

Question 52

What is the benefit in measuring cTSH after starting treatment for hypothyroidism?

Answer 52

provides a long-term assessment vs TT4 is a snapshot in time

Question 53

Clinical signs of thyrotoxicosis

Answer 53

PU/PD/PP panting weight loss hyperactivity tachycardia hyperthermia **this is RARE, up to 10x the standard dose is well tolerated

Question 54

a rare, life-threatening condition in dogs that occurs when the body's thyroid hormones are severely low. Symptoms include lethargy, confusion, and difficulty breathing; "sad face"

Answer 54

myxedema coma

Question 55

Myxedema coma is a life-threatening emergency. How would you go about treating this/ how soon should you expect to see a response?

Answer 55

5 mcg/kg IV q12, not transitioning to orals until condition has stabilized abnormal mentation, ambulation and systolic hypotension should resolve within 30h

Question 56

Differentials for feline hypothyroidism

Answer 56

iatrogenic hypothyroidism* non-thyroidal illness syndrome (NTIS) naturally occurring (congenital/ adult onset) is rare

Question 57

T/F: Adult onset hypothyroidism is more common than congenital in cats.

Answer 57

F - congenital hypothyroidism is recognized more frequently

Question 58

Differentials for feline congenital hypothyroidism

Answer 58

1. thyroid dyshormonogenesis (thyroid peroxidase deficiency and iodid transport defects)* 2. thyroid hypolasia/aplasia 3. Thyrotropin resistance 4. Thyroiditis

Question 59

Sequelae of radioactive iodine treatment in cats - clients love numbers

Answer 59

overt hypothyroidism after 6mo, 1-40% subclinical hypothyroidism, 13-40%

Question 60

Sequelae of thyroidectomy treatment in cats - clients love numbers

Answer 60

unilateral - not expected bilateral - ~50% become hypothyroid **transient euthyroidism is expected in 2-3 mo

Question 61

Feline adult-onset hypothyroidism - Clinical signs

Answer 61

lethargy inappetence mental dullness dermatologic abnormalities obesity PU/PD

Question 62

Feline congenital hypothyroidism - Clinical signs

Answer 62

Normal at birth, but slow growth becomes evident by 6-8 weeks of age large heads short wide neck short body short thick limbs palpable goiter obesity lethargy mental dullness constipation hypothermia bradycardia retention of teeth/ delayed eruption of teeth coat - mainly undercoat with primary guard hairs scattered thinly

Question 63

What is the sequelae of subclinical hypothyroidism in cats?

Answer 63

increased risk of azotemia (esp given the prevalence of CKD) **MST for azotemic cats with untreated hypothyroidism was 456 vs 905 that of euthyroid azotemic cats (Williams et al 2010)

Question 64

Indications for treating iatrogenic hypothyroidism.

Answer 64

Clinical signs azotemia hypothyroidism does not resolve within 3-6mo of treatment (thyroidectomy, radioactive iodine tx)