Richard W. Nelson, DVM, DACVIM
Recommendations regarding the approach to the diagnosis of hypothyroidism are given in Table 1. The presence of appropriate clinical signs is imperative, especially when relying on baseline thyroid hormone concentrations for a diagnosis. Identification of a mild nonregenerative anemia on the CBC and especially an increased serum cholesterol concentration on a serum biochemistry panel adds further evidence for hypothyroidism. Baseline serum total thyroxine (T4) concentration is often used as the initial screening test for thyroid gland function, in part, because it is widely available at low cost and can be measured in-house. It is important to remember that serum T4 concentrations can be suppressed by a variety of factors, most notably the euthyroid sick syndrome. As such, measurement of the serum T4 concentration should be used to confirm a euthyroid state. A normal serum T4 concentration establishes euthyroidism in the vast majority of dogs. The exception is a very small number of hypothyroid dogs with lymphocytic thyroiditis that have serum T4 autoantibodies that interfere with the RIA used to measure T4. A low serum T4concentration (i.e., < 7 nmol/l) in conjunction with hypercholesterolemia and clinical signs strongly suggestive of the disease supports the diagnosis of hypothyroidism, especially if systemic illness is not present. The definitive diagnosis must then rely on response to trial therapy with levothyroxine sodium. Additional diagnostic tests (i.e., free thyroxine (fT4) and thyrotropin (TSH)) are warranted if the serum T4 concentration is less than 13 nmol/l but clinical signs and physical examination findings are not strongly supportive of the disease and hypercholesterolemia is not present, if severe systemic illness is present and the potential for the euthyroid sick syndrome is high, or if drugs known to decrease serum T4 concentration are being administered.
Although measurement of serum T4 concentration can be used as an initial screening test, measuring a combination of thyroid gland tests provides a more informative analysis of the pituitary-thyroid gland axis and thyroid gland function and is preferred. Many diagnostic laboratories offer a variety of options in thyroid panels that incorporate two or more of the following: serum T4, fT4 determined by radioimmunoassay or modified equilibrium dialysis (MED), total and free triiodothyronine (T3 ), reverse T3 , TSH, and antibody tests for lymphocytic thyroiditis. The thyroid panel at our hospital includes serum T4, fT4 by MED, TSH, and the thyroglobulin (Tg) autoantibody test. A normal serum T4 , fT4 , and TSH concentration rules out hypothyroidism. Low serum T4 and fT4 and increased serum TSH concentrations in a dog with appropriate clinical signs and clinicopathologic abnormalities strongly supports the diagnosis of hypothyroidism, especially if systemic illness or drugs known to affect thyroid test results are not present. Concurrent presence of Tg autoantibodies suggests lymphocytic thyroiditis as the underlying etiology.
Unfortunately, discordant test results are common when multiple tests are evaluated and this can create confusion. When this occurs, reliance on appropriateness of clinical signs, clinicopathologic abnormalities, and clinician index of suspicion become the most important parameters when deciding whether to treat the dog with levothyroxine sodium. Serum fT4 concentration measured by MED is the single most accurate test of thyroid gland function and carries the highest priority when assessing thyroid gland function, followed by serum T4 concentration. Results of TSH concentration increases the likelihood of euthyroidism or hypothyroidism when results are consistent with results of serum fT4, but TSH test results should not be used as the sole indicator of hypothyroidism. Low serum fT4 and normal TSH test results occur in approximately 20% of dogs with hypothyroidism and high TSH test results occur in euthyroid dogs with the euthyroid sick syndrome. Normal serum fT4 and high TSH may suggest early compensated hypothyroidism but one has to wonder why clinical signs would develop if serum fT4 is normal. A positive Tg autoantibody test merely suggests the possibility of lymphocytic thyroiditis; Tg autoantibody is not a thyroid function test. Positive results increase the suspicion for hypothyroidism if serum T4 or fT4 concentrations are low but have no bearing on generation of clinical signs if serum T4 and fT4 concentrations are normal. Positive serum T4 and T3autoantibody test results are interpreted in a similar manner. When faced with discordant test results, the decision becomes one of initiating trial therapy with levothyroxine sodium or repeating the tests sometime in the future; a decision which we ultimately make based on the appropriateness of clinical signs and results of the serum fT4 concentration measured by MED.
Admittedly, interpretation of serum T4, fT4, and TSH concentrations is not always simple. Because of expense and the frustration of working with tests that can fail to be reliable, many veterinarians and some clients prefer trial therapy as a diagnostic test. Trial therapy should only be done when thyroid hormone supplementation does not pose a risk to the patient. Response to trial therapy with levothyroxine sodium is non-specific. A dog that has a positive response to therapy either had hypothyroidism or had "thyroid-responsive disease". Because of its anabolic nature, thyroid hormone supplementation can create an effect in a dog without thyroid dysfunction. This is perhaps most notable in the quality of the hair coat. Thyroid hormone supplementation stimulates telogen hair follicles into the anagen stage and improves the hair coat, presumably even in euthyroid dogs. Therefore, if a positive response to trial therapy is observed, thyroid supplementation should be gradually discontinued once clinical signs have resolved. If clinical signs recur, hypothyroidism is confirmed and the supplement should be reinitiated. If clinical signs do not recur, a "thyroid-responsive disorder" or a beneficial response to concurrent therapy (e.g., antibiotics, flea control) should be suspected.
Table 1. Diagnostic recommendations for evaluating thyroid gland function in the dog
1. The decision to assess thyroid gland function should be based on the history, physical examination, and results of routine bloodwork (CBC, serum biochemistry panel, urinalysis)
2. Initial single screening tests include baseline serum T4 and baseline serum free T4 measured by equilibrium dialysis (MED).
a. Treatment is indicated if the serum T4 or free T4 concentration is low and the initial evaluation of the dog strongly supports the diagnosis of hypothyroidism.
b. Treatment is not indicated if the serum T4 or free T4 concentration is normal and the initial evaluation of the dog does not strongly support the diagnosis of hypothyroidism.
c. Additional diagnostic tests (i.e., endogenous TSH, thyroglobulin or thyroid hormone autoantibody) are indicated if serum T4 concentration is normal but the initial evaluation of the dog strongly supports the diagnosis of hypothyroidism--or the veterinarian is uncertain if hypothyroidism exists after evaluation of history, physical examination, routine bloodwork, and serum T4 or free T4 concentration.
3. Commonly used screening protocols utilizing two diagnostic tests include baseline serum T4 or baseline serum free T4 measured by MED and serum TSH concentration.
a. Treatment is indicated if the serum T4 or free T4 concentration is low and the initial evaluation of the dog strongly supports the diagnosis of hypothyroidism, regardless of the serum TSH test result.
b. Treatment is not indicated if all of these tests are normal and the initial evaluation of the dog does not strongly support the diagnosis of hypothyroidism.
c. Treatment is not indicated and the tests should be repeated in 8 to 12 weeks if the serum free T4 concentration is normal and the serum TSH concentration is increased.
d. Evaluation of serum thyroglobulin or T4 autoantibody test is indicated if serum T4 concentration is normal, serum TSH concentration is increased, and the initial evaluation of the dog strongly supports the diagnosis of hypothyroidism.
4. Common components of a thyroid panel include serum T4 concentration, serum T4 concentration measured by MED, serum TSH concentration, and an antibody test for lymphocytic thyroiditis.
a. Treatment is indicated if all of the tests for thyroid gland function are abnormal and the initial evaluation of the dog strongly supports the diagnosis of hypothyroidism, regardless of the thyroid hormone antibody test results.
b. Treatment is not indicated if all of the tests for thyroid gland function are normal and the initial evaluation of the dog does not strongly support the diagnosis of hypothyroidism, regardless of the thyroid hormone antibody test results. Positive thyroid hormone antibody test results support the presence of lymphocytic thyroiditis and the need to monitor tests of thyroid gland function every 3 to 6 months.
c. When discordant thyroid gland function test results are obtained, the decision to treat should be based on the initial evaluation of the dog, the clinician's index of suspicion for hypothyroidism, and a critical evaluation of each thyroid gland function test result. Serum free T4 concentration by MED is the most accurate test of thyroid gland function.