Laboratory Evaluation of Canine Hypothyroidism

Robert Lobingier, DVM, DAVCP Clinical Pathologist IVS Portland, OR
January 2000

Canine Hypothyroidism is the most common endocrinopathy in canine medicine. Hypothyroidism is also considered the most commonly over-diagnosed endocrine disorder. It is a disease that can be difficult to confirm, but relatively easy to treat.

As with most endocrinopathies, a convincing pattern of disease with both strong clinical signs and consistent laboratory findings is essential in the diagnosis of Canine Hypothyroidism. The understanding, selection, and interpretation of laboratory tests can be essential to both assess thyroid function and confirm the diagnosis of hypothyroidism.

General Laboratory Tests

General laboratory findings are an important part of the initial workup for the suspected hypothyroid patient. A Complete Blood Count and Serum Biochemical Profile will not only aid in ruling out possible underlying nonthyroidal disease, but should increase the probability of hypothyroidism. Approximately 75% of hypothyroid dogs will have serum cholesterol levels in excess of 400 mg/d and 30% will exhibit mild to moderate nonregenerative anemia.

Total Serum T4

Basal thyroid screening most often involves an initial Total serum T4 (TT4) measurement. It is an excellent screening test because it is a sensitive, relatively inexpensive, and readily available. The TT4 primarily measures the protein bound fraction of thyroid prohormone that is not directly available for cellular metabolism. The T4 measurement routinely done in laboratories measures only the potential reservoir of hormone. The free fraction of T4 (FT4) makes up less than 1% of the T4 in circulation but it is the biological available fraction able to enter cells. Relatively large fluctuations of the Total T4 reservoir can occur with little impact on the free fraction and cellular metabolism.

The TT4 is broadly influenced by the presence of nonthyroidal disease and certain drugs which will cause a decrease in serum levels of TT4. Approximately 75% of dogs ill with nonthyroid related disease will have TT4 at the low end of or below normal range. A similar result can be found in dogs with spontaneous Cushing's disease. Drugs that can induce suppression of serum thyroid hormone levels include glucocorticoids, anticonvulsants, and nonsteroidal anti-inflammatory drugs. In light of the above information, TT4 measurement is much more reliable in reassuring a euthyroid state (with values >1.5 - 2.0 g/ dl).

Conclusion: TT4 is an excellent screening test that is very good at reassuring euthyroidism but often not reliable in confirming hypothyroidism.

Total Serum T3

Total serum T3 (TT3) measurement has been used in conjunction with TT4 in an attempt to improve the reliability of thyroid evaluation. TT3 is the major active hormone at the cellular level formed by deiodinization of T4; however, TT3 is a minor product of the thyroid gland there is a broad overlap in serum levels when populations of euthyroid, hypothyroid, and sick euthyroid dogs. TT3 is considered both relatively insensitive and often nonspecific in assessment of hypothyroidism.

Conclusion: TT3 is one of the least reliable indicators of thyroid function and is of minimal value in assessment of thyroid function in the dog.

Confirmatory Tests

Confirmatory testing for hypothyroidism can involve two relatively new tests that improve the accuracy of laboratory diagnosis. The measurement of the free fraction of T4 by the equilibrium dialysis method (FT4 ED) has been shown to be a very sensitive and specific measure of thyroid function. The FT4 ED analysis is much less influenced by nonthyroidal factors with sensitivity and specificity greater than 90% over a broad range of patients.

The canine endogenous TSH assay (cTSH) is a test intended to increase the accuracy in diagnosis of primary hypothyroidism. With a decline in thyroid function (and negative feedback to the pituitary gland), cTSH levels should consistently increase; however, current diagnostic performance of cTSH has been somewhat disappointing with sensitivity and specificity much less than FT4ED and TT4. The cTSH can be useful when used in combination with the FT4ED. The combined specificity can exceed 95% making this combination very useful in confirming hypothyroidism in difficult or unclear cases.

Conclusion: FT4ED is a very accurate test for evaluating basal thyroid function and is an important test in confirming hypothyroidism. When a below normal FT4ED level is combined with an elevated cTSH in a patient, canine hypothyroidism is extremely likely.

Other laboratory tests for hypothyroidism include: antiT4 and antiT3 antibody, and antithyroglobulin antibody (ATA or TgAA). These tests propose to evaluate patients for immune mediated thyroid disease and positive results do have an increased statistical correlation with lymphocytic thyroiditis (particularly ATA). These tests do not relate directly to thyroid function and the overall diagnostic accuracy and utility of immune thyroid testing has yet to be shown. Positive results occur in many patients with no evidence of thyroid related disease. Interpretation of these tests must be done with some caution. The overall predictive value and utility of these tests in any broad screening program for potential thyroid related disease will require further investigation.

Conclusion: Measuring antibodies against thyroid hormones or thyroglobulin does not test thyroid function but does show correlation with the presence of lymphocytic thyroiditis. Overall clinical significance of these tests in the general canine population will require further study.

Confirming the Diagnosis

The final, and most important, step in the confirmation of hypothyroidism is in response to supplementation.

Treatment with sodium levothyroxine (L-thyroxine) is usually initiated on a divided daily dosage schedule. Dramatic clinical improvement in related signs should occur within 2-4 weeks of therapy with more chronic skin and coat changes possibly taking several months to resolve. 6-8 weeks of therapy should prove to be an adequate time frame to assess patient response in any therapeutic trial. Therapeutic drug monitoring for TT4 supplementation should be performed 2-4 weeks after initiating therapy with peak levels measured 4-6 hours post pill. Serum TT4 measurement is usually the test of choice to monitor therapy with peak levels near the high end of normal range . It is interesting to note that Thyroid supplementation in euthyroid patients can result in temporary improvement in conditions such as alopecia by stimulating an androgenic response. Therefore, when assessing a therapeutic trial, there should be close and objective monitoring for dramatic and lasting clinical improvement.

Final Thoughts

The definitive diagnosis of canine hypothyroidism requires not only a complete clinical and laboratory assessment, but also a documentation of response to therapy and remission of clinical signs. Careful consideration of clinical signs that may mimic thyroid related disease and confuse the diagnosis should always be part of this diagnostic plan. The TT4 measurement is a good screening test because of its sensitivity to disease but can be a poor confirmatory test due to its lower specificity. More accurate confirmatory tests are now available that should be considered to aid the diagnosis. A final diagnosis of hypothyroidism in a patient means the patient will require lifelong therapy. Inappropriate supplementation in a euthyroid canine will lead to unnecessary expense, a delay in a more appropriate diagnosis, and the potential for inducing secondary hypothyroidism.

References and additional reading:

1. Chastain CB and Panciera DL: Hypothyroid Diseases. In Ettinger (ed): Textbook of Veterinary Internal Medicine. 4th ed. 1995, pp 1487- 1501
2. Scott DW, et. al.: Endocrine and Metabolic Diseases. In Muller and Kirk?s Small Animal Dermatology. 5th ed. 1995. pp 691 - 703
3. Feldman EC and Nelson RW: Hypothyroidism. In Canine and Feline Endocrinology and Reproduction. 2nd ed. 1996  pp 68 - 117
4. Nichols, R: Update: Diagnostic Testing for Canine Hypothyroidism. 15th Annual ACVIM Forum, Lake Buena Vista, FL 1997
5. Melian C. et al.: Evaluation of Free T4 and Endogenous TSH as Diagnostic Tests for Hypothyroidism in Dogs. 15th Annual ACVIM Forum, Lake Buena Vista,FL. 1997