Exam 8: L4: Hypothyroidism

Question 1

Note

Answer 1

Hypothyroidism is the most commonly described endocrine disorder of the dog!
-However this may reflect over diagnosis

Question 2

Regulation of thyroid hormone

Answer 2

TSH = major modulator of thyroid activity

-from anterior pituitary

Question 3

Thyroid hormone biology

Answer 3

1) plasma hormones are largely bound to proteins
- protein bound hormone serves as a large reservoir
2) <1% of T3 and T4 circulate free/unbound*
3) FREE hormone enter cells, produces its biologic effects, then is metabolized
4) **ONLY FREE hormone regulates the feedback mechanism
5) T4 (thyroxine) is the main secretory product of the thyroid gland!
6) most T3 is derived from T4 in peripheral tissues
- T3 IS ACTIVE HORMONE
- <20% of T3 is produced in the thyroid gland

Question 4

T3 diagnosis for hypothyroidism?

Answer 4

No, we usually do not look at T3 for diagnosis of hypothyroidism

Question 5

Canine hypothyroidism: classification

Answer 5

1) based on the location of the problem within the gland complex
- primary = thyroid problem (most common in the dog ~95%)
- secondary = impaired secretion of TSH by the anterior pituitary
- tertiary = deficient TRH secretion by hypothalamus

Question 6

Primary hypothyroidism

Answer 6

1) Irreversible destruction of the thyroid gland
2) histologically, there are 2 main categories (1:1 ratio):
- lymphocytic thyroiditis (a.k.a. autoimmune thyroiditis)
- idiopathic thyroid degeneration (a.k.a. follicular atrophy; loss of thyroid parenchyma and replacement by adipose and fibrous tissue)

Question 7

Clinical signs

Answer 7

1) variable, but:
- mental dullness
- lethargy
- exercise intolerance
- weight gain (without increase in food intake)
- heatseeking
- skin/hair coat changes
2) onset is gradual and subtle!!
3) due to decreased cellular metabolism**
4) neuromuscular signs due to segmental demyelination and axonopathy

Question 8

Hypothyroidism clinical signs: skin/haircoat

Answer 8

1) alterations in skin and hair coat are the most commonly observed signs in dogs with hypothyroidism
2) skin changes can be quite varied
3) bilaterally symmetric, nonpruritic truncal alopecia
4) failure to regrow hair after clipping
5) classic “rat tail”
6) sebaceous gland atrophy, hyperkeratosis, scales, dry and lusterless hair coat, hyperpigmentation

Question 9

Clinicopathologic abnormalities of hypothyroidism

Answer 9

1) biochemistry profile
- fasting hypercholesterolemia (>75% of dogs)
- fasting hypertriglyceridemia
- mechanism: degradation of lipids is suppressed*
- **presence of hypercholesterolemia with appropriate clinical signs is strongly supportive
2) urinalysis
- usually normal
- dogs with lymphoplasmacytic thyroiditis may have proteinuria (secondary to immune complex glomerulonephritis)

Question 10

Total T4 by radioimmunoassay

Answer 10

1) screening test!
2) only diagnostic when the value is normal or elevated**
3) you can essentially RULE OUT hypothyroidism with a normal value
- approximately 10% of hypothyroid dogs are missed if you rely solely on TT4 screening (due to the presence of anti-T4 antibodies = = >T4 antibodies may cause a falsely increased T4 value)
4) a value below normal does NOT equate to hypothyroidism
- *non-thyroidal illness and drugs can also lower TT4

Question 11

Effect of non-thyroidal illness on TT4

Answer 11

1) many other illnesses and drugs can lower baseline serum TT4 or TT3
2) *many times serum fT4 by dialysis is not affected, but sometimes it is
3) reductions in thyroid hormone concentrations with NTI serve to protect against the catabolism of illness
4) it is inappropriate to correct states of low thyroid concentration, due to NTI, with thyroid hormone

Question 12

Free thyroxine (fT4) concentrations

Answer 12

1) direct dialysis or equilibrium dialysis (DD or ED)
- “gold standard” for the measurement of fT4
- only the dialysis method provides the additional information needed to distinguish animals with low TT4 due to NTI, from those with actual hypothyroidism

Question 13

Serum thyrotropin (TSH) concentrations

Answer 13

1) a dog with primary hypothyroidism would be expected to have an elevated TSH
- up to 25% of dogs may have normal TSH values
- elevated TSH is highly specific for primary hypothyroidism
2) TSH should not be used alone as a screening test!
3) it does add specificity to an observation of a low TT4/fT4

Question 14

Complicating factors

Answer 14

1) NTI results in depression of TT4 and TT3, with a reduction in fT4ED only in the most severe illnesses
2) distinguishing NTI from hypothyroidism: CLINICAL ASSESSMENT OF THE ANIMAL

3) it is inappropriate to start thyroid supplementation based on the sole observation of a low TT4 without clinical signs consistent with hypothyroidism!

Question 15

Effect of drugs

Answer 15

The following may decrease TT4, fT4, and/or TSH:

1) glucocorticoids
2) phenobarbital
3) sulfonamides
4) carpofren

Question 16

Summary for optimal testing sequence

Answer 16

1) normal fT4ED and TSH values almost always identify an euthyroid animal
2) low TT4 or fT4ED, together with high TSH, confirms hypothyroidism in most cases

Question 17

Monitoring response to treatment

Answer 17

1) critically evaluate treatment after 6-8 weeks of supplementation
2) with appropriate treatment, all clinical signs of hypothyroidism are reversible
3) measure T4 and TSH 4-6 hours after administration of supplementation
- post-dose T4 should be in the upper half or above the reference range = = >this is the peak
- TSH should be in the reference range

Question 18

Remember

Answer 18

TT4 is a SCREENING TEST = a normal value essentially rules out hypothyroidism, a low value means additional testing is needed