Hypothyroidism - Dogs & Cats Flashcards
Ettinger Ch 285, 286
______ is a large glycoprotein containing iodotyrosines, precursors of thyroid hormones.
Thyroglobulin (stored in colloid)
What hormone(s) does the thyroid gland synthesize and secrete?
thyroxine = T4
triodothyronine = T3
T/F: Thyroid hormones are bound to albumin and not globulin.
F - 60% of T4 & T3 are bound to thyroxine binding globulin, 17% to transthyretin, 12% to albumin and 11% to various lipoproteins
In health, when thyroid levels are low the hypothalamus secretes _____ to promote the anterior pituitary to release _________.
thyrotropin releasing hormone (TRH)
thyrotropin stimulating hormone (TSH)
What are the functions of thyroid hormones? (7)
metabolic rate
growth
nervous system development
tissue turnover
cardiac - inotropic, chronotropic
lipid synthesis & metabolism
erythropoiesis
What is the functional unit of the thyroid gland? Describe what is contained intra- and extra-cellularly.
thyroid follicle
intra = colloid, which stores thyroglobulin
extra = thyroid hormone (T3, T4)
What is the role of thyroid peroxidase (TPO) in thyroid hormone synthesis?
oxidation of iodide to iodine
facilitates iodine organification = iodination of tyrosyl residues on thyroglobulin
What are the 3 categories of hypothyroidism?
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)
Congenital hypothyroidism is rare. What breed of dogs has central hypothyroidism been reported in?
Schnauzers, giant/mini
Congenital hypothyroidism is rare. which breed(s) of dog(s) have dyshormonogenesis and thyroperodisase deficiency been reported in?
frenchies
spanish water dogs
teterfields
toy fox
rat terriers
Congenital hypothyroidism is rare. Which breed(s) of dog(s) has congenital hypothyroidism been reported in due to sodium-iodide symporter (NIS) deficiency?
Papillons
Shih Tzus
Central hypothyroidism is rare. What is the most common cause of central hypothyroidism?
Pituitary neoplasia
Surgical hypophysectomy
What are the most common causes of hypothyroidism in the dog?
lympochytic thyroiditis
idiopathic thyroid atrophy
What drugs have been implicated in causing hypothyroidism?
potentiated sulphonamides
toceranib (Palladia)
pred
phenobarbital
clompiramine
carprofen
What are the benefits in running a thyroglobulin autoantibody (TgAA) test?
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
Hypothyroidism - Signalment
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)
Hypothyroidism - Clinical Signs
> 80% = lethargy, weight gain, exercise intolerance, mental dullness, cold intolerance, generalized weakness, shivering
40-50% = overweight, obese
80% = endocrine alopecia
Describe endocrine alopecia
non-pruritic
bilaterally symmetric
tendency to spare the head and extremities
T/F: Pyoderma is a common sequelae of hypothyroidism.
F - <10% of dogs with recurrent pyoderma are diagnosed with hypothyroidism
T/F: Hypothyroidism is associated with the development of adult-onset demodicosis.
True
artherosclerosis
condition that occurs due to a build up in cholesterol, calcium, other substances
**few reports of aortic thromboembolism and severe atherosclerosis associated with hypothyroidism
Proposed mechanisms of hypothyroidism and gallbladder mucoceles.
dyslipidemia
gallbladder dysmotility
altered bile acid composition
decreased bile flow
biliary stasis
Clinical features of congenital hypothyroidism.
disproportionally wide skulls
macroglossia (large tongue)
delayed dental eruption
square trunk
short limbs
+/- constipation
mental impairment
+/- goiter
CBC findings - Hypothyroidism
Mild NNN anemia (“physiologic anemia”- 50%
Leukocytosis is unusual
Why can hypothyroidism cause a, “physiologic anemia”?
- decreased EPO production
- Lack of direct stimulatory effect of T3/T4 on bone marrow
Serum biochemistry findings - Hypothyroidism
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%
Why does hypothyroidism result in hypercholesterolemia and hypertriglyceridemia?
T3/T4 stimulates all aspects of lipid metabolism (synthesis, mobilization, degradation)
**degradation is severely affected, resulting in lipid accumulation
How can sample timing (circadian rhythm), age and sex impact thyroid hormone secretion?
+/- 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)
Which breed of dogs are known to have low circulating TT4?
Sight hounds:
Greyhounds - 90%
Basenjis - 75%
Sloughis - 65%
Whippets - 35%
Scottish Deerhounds - 5%
Which breed of dogs can have low TT3 levels?
Salukies
Irish Wolfounds
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.
TT3 - mildly decreased
TT4 - unchanged
fT4 - unchanged
TSH - unchanged
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.
TT3 - mod decreased
TT4 - mildly decreased
fT4 - anything
TSH - unchanged/ decreased
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.
TT3 - severely decreased
TT4 - mod decreased
fT4 - unchanged/ decreased
TSH - mod decreased
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.
TT3 - unchanged/decreased
TT4 - unchanged/decreased
fT4 - unchanged/decreased
TSH - unchanged/increased
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.
TT4 - unchanged/ decreased
fT4 - unchanged/ decreased
TSH - unchanged/ decreased
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.
TT4 - unchanged/ decreased
fT4 - unchanged/ decreased
TSH - anything*
*associated with increased TSH without exceeding upper reference limit
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.
TT4 - decreased
fT4 - decreased
TSH - increased
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.
TT4 - decreased
fT4 - decreased
TSH - increased
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.
TT4 - unchanged/ decreased
fT4 - unchanged/ decreased
TSH - unchanged/ decreased
Why is TT3 of limited value for diagnosing hypothyroidism?
low diagnostic sensitivity
TT3 are WNL or above RIs in 90% of hypothyroid dogs
When would you measure TT3 in dogs?
In breeds known to have low TT4, should have normal TT3 = Greyhounds
What is the most frequently recommended screening test for hypothyroidism? What can falsely elevate this value?
TT4
T4AA’s can falsely increase measured values - 14% of dogs with hypothyroidism
What is the most specific/ accurate test in diagnosing hypothyroidism in dogs?
fT4 - equilibrium dialysis, less affected by extrathyroidal factors (vs TT4)
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?
TT4 <1.7
100% sensitive
>90% specific
Explain why synthetic T3 is not the treatment of choice for canine hypothyroidism?
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
When is the soonest you can measure thyroid levels after starting thyroid supplementation?
2-weeks = steady state
Sequelae of thyroid supplementation - i.e, what should you warn clients about when you start treatment for hypothyroidism?
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
What clincopathology changes do you expect to see when starting treatment for hypothyroidism?
- improvement in cholesterol and triglycride
- increase in RBC during first 3mo
- fructosamine decreases (protein turnover increases)
- improvement in creatinine, SDMA
When monitoring TT4 after starting treatment, what value is usually associated with an inadequate clinical response/ should prompt you to INCREASE the dose?
<2.7 mcg/dL (35 nmol/L)
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?
7-7.8 mcg/dL (90-100nmol/L), or greater
What is the goal TT4 after initiating treatment for hypothyroidism?
high end/ just above reference interval
What is the benefit in measuring cTSH after starting treatment for hypothyroidism?
provides a long-term assessment vs TT4 is a snapshot in time
Clinical signs of thyrotoxicosis
PU/PD/PP
panting
weight loss
hyperactivity
tachycardia
hyperthermia
**this is RARE, up to 10x the standard dose is well tolerated
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”
myxedema coma
Myxedema coma is a life-threatening emergency. How would you go about treating this/ how soon should you expect to see a response?
5 mcg/kg IV q12, not transitioning to orals until condition has stabilized
abnormal mentation, ambulation and systolic hypotension should resolve within 30h
Differentials for feline hypothyroidism
iatrogenic hypothyroidism*
non-thyroidal illness syndrome (NTIS)
naturally occurring (congenital/ adult onset) is rare
T/F: Adult onset hypothyroidism is more common than congenital in cats.
F - congenital hypothyroidism is recognized more frequently
Differentials for feline congenital hypothyroidism
- thyroid dyshormonogenesis (thyroid peroxidase deficiency and iodid transport defects)*
- thyroid hypolasia/aplasia
- Thyrotropin resistance
- Thyroiditis
Sequelae of radioactive iodine treatment in cats - clients love numbers
overt hypothyroidism after 6mo, 1-40%
subclinical hypothyroidism, 13-40%
Sequelae of thyroidectomy treatment in cats - clients love numbers
unilateral - not expected
bilateral - ~50% become hypothyroid
**transient euthyroidism is expected in 2-3 mo
Feline adult-onset hypothyroidism - Clinical signs
lethargy
inappetence
mental dullness
dermatologic abnormalities
obesity
PU/PD
Feline congenital hypothyroidism - Clinical signs
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
What is the sequelae of subclinical hypothyroidism in cats?
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)
Indications for treating iatrogenic hypothyroidism.
Clinical signs
azotemia
hypothyroidism does not resolve within 3-6mo of treatment (thyroidectomy, radioactive iodine tx)
