How to Test, Interpret Thyroid Function
Posted: April 12, 2 p.m., EDT
By W. Jean Dodds, DVM
For Veterinary Practice News
Hypothyroidism is the most common endocrine disorder of dogs. More than 80 percent of cases result from autoimmune thyroiditis, the heritable autoimmune disease that progressively destroys the thyroid gland.
Classical clinical signs of hypothyroidism only appear once more than 70 percent of the gland is destroyed. Accurate diagnosis may be difficult because thyroid dysfunction produces a wide range of clinical signs, many of which are subtle and mimic those of other causes.
Hyperthyroidism is a common endocrine disorder of older cats. Diagnosis can be confounded by concurrent kidney, gastrointestinal and liver disease, as total T4 concentration can be suppressed into the normal reference range.
To facilitate diagnosis of thyroid disorders, veterinarians need to routinely employ more complete thyroid profiles, and there is a need to balance affordability with accuracy.
Total T4: Measures bound
(> 99 percent) and unbound
(< 1 percent) circulating T4.
While T4 is the most widely used initial screening test for thyroid disorders, relying on this test alone is a primary reason for the misdiagnosis of canine and feline thyroid disorders. T4 concentration is affected by non-thyroidal illness (NTI) and certain medications (e.g. phenobarbital, corticosteroids and sulfonamides), and it fails to detect autoimmune thyroiditis.
FreeT4: Serum freeT4 represents the tiny unbound fraction (< 0.1 percent) of biologically active thyroxine. It is much less likely to be influenced by NTI or drugs, and so is a more accurate test of thyroid activity. While some prefer the equilibrium dialysis (ED) RIA method for measuring freeT4, newer technologies (improved analog RIAs and non-RIA methods) offer alternative, accurate methodology. These new assays are faster and less costly.
Total T3: Represents both the bound and unbound forms of circulating T3. Measuring serum T3 alone is not accurate for diagnosing thyroid disorders, as it is influenced by NTI. But it is still useful as part of a thyroid panel. If total T3 levels are very high (or very low, if measured at MSU) in a dog not taking thyroxine, the patient most likely has a circulating T3 autoantibody, spuriously affecting the results.
FreeT3: Measures the tiny biologically active fraction of T3. Levels may be elevated slightly in euthyroid dogs or cats with increased tissue metabolic demands, and are typically spuriously high in dogs with T3 autoantibodies. Both total T3 and freeT3 should be normal in hypothyroidism, unless the dog has concurrent NTI.
Canine thyroglobulin autoantibodies (TgAA): Elevated thyroglobulin autoantibodies are usually present in the serum of dogs with autoimmune thyroiditis, the heritable form of hypothyroidism. TgAA is important in screening breeding stock, as dogs testing positive for TgAA should not be bred.
The commercial TgAA test can give false negative results if the dog has received thyroid supplement within the previous 90 days, thereby allowing unscrupulous people to test dogs while on treatment to assert their normalcy, or to obtain certification with health registries such as the OFA Thyroid Registry.
False negative TgAA results can also occur in ~8 percent of dogs verified to have high T3 and/or T4 autoantibodies. Furthermore, false positive TgAA results may be obtained if the dog has been vaccinated within the previous 30 to 45 days for rabies, or occasionally in cases of NTI.
T3 Autoantibody (T3AA)/ T4 Autoantibody (T4AA):
These autoantibodies affect the accurate measurement of T4 and T3. Results may be spuriously high (or low, if measured at MSU) for T3 and freeT3 or T4 and freeT4. However, if the freeT4 is measured by the ED technique, the T4AA will be removed by the dialysis step and not be detected. Fortunately, most circulating antibodies are against T3 (~70 percent), some affect both T3 and T4 (~25 percent), and only a few affect T4 alone (~5 percent).
Endogenous Canine TSH (Thyroid Stimulating Hormone)
In primary hypothyroidism, as freeT4 levels fall, pituitary output of TSH rises. About 95 percent of thyroid hormone regulation in humans is controlled by TSH, so it offers accurate screening for hypothyroidism. In dogs, only ~70 percent of thyroid hormone regulation is controlled by TSH, so this test has relatively poor predictability of primary hypothyroidism.
The remaining 30 percent of canine thyroid regulation is controlled by growth hormone. So, although elevated cTSH usually indicates primary thyroid disease, ~30 percent discordance is observed between expected and actual results in normal dogs, hypothyroid dogs and those with NTI or pituitary-dependent hypothyroidism.
In geriatric cats, cTSH concentrations are typically very low and can be predictive of incipient hyperthyroidism.
More Thyroid Diagnostics
Basal thyroid levels are not the same for dogs over the age and breed spectrum.
• Puppies have higher basal thyroid levels than adults.
• Geriatrics have lower basal thyroid levels than adults.
• Large/giant breeds have lower basal thyroid levels.
• Sighthounds as a group have much lower basal thyroid levels.
• Situations That Affect Basal Thyroid Activity
• Basal levels affected by certain drugs.
• Basal levels lowered by estrogen; raised by progesterone. Test during anestrus.
• Thyroid levels are suppressed up to 25 percent by corticosteroids, sulfonamides, overdosing iodine (kelp) and phenobarbital.
• Rabies vaccination within previous 45 days can elevate TgAA by ~25 percent.
A minimum of six weeks without thyroxine is needed before an accurate assessment of basal thyroid capacity can be made.
Screening for Canine Autoimmune Thyroiditis
Dogs taking thyroxine must be off this drug for at least 90 days to get accurate TgAA results. Testing requires:
• Complete thyroid antibody profile.
• Test intact females during anestrus.
• Need TgAA, +/- T3AA & T4AA; not just freeT4, cTSH, TgAA.
• OFA Thyroid Registry is only a limited panel.
• About 8 percent of TgAA negative cases are T3AA and/or T4AA positive.
Testing Older Cats
• Testing older cats is similar to older dogs.
• Basal thyroid levels in older cats should be lower than adults.
• Other illnesses often lower T4, masking hyperthyroidism.
• Minimum testing needed is T4 and freeT4.
• FT4 by ED method can be high in cases of GI, renal, and liver disease.
Dr. Dodds is founder of Hemopet, a full-service laboratory and non-profit veterinary blood bank in Garden Grove, Calif. Hemopet conducts advanced canine diagnostic thyroid testing for clients around the world. Dr. Dodds is a 1964 graduate of Ontario Veterinary College.