The image we have of canine hypothyroidism has changed during the last decade. We use to consider it as the most common endocrinopathy in dogs. Most endocrinologists will agree that nowadays, other endocrine diseases such as hypercortisolism, are more frequently observed. In the past, many dogs have been erroneously diagnosed with hypothyroidism. Indeed, evaluation of thyroid function in dogs is not always straightforward. The vague and non-specific clinical signs of hypothyroidism and the fact that numerous factors can influence thyroid function test results are major contributors to the difficulty in diagnosing this disease.

Tests Available to Assess the Thyroid Gland in Dogs

Table. Advantages and disadvantages of the most commonly used tests to evaluate thyroid function in dogs.

SNTD: systemic non-thyroid disease

Total Thyroxine (TT4)

It is important to realise the limitations of a TT4 measurement. Indeed, numerous factors such as systemic diseases (euthyroid sick syndrome) or the administration of medications can influence the TT4 serum concentrations. Therefore, when TT4 serum concentration is below the reference range, further testing is indicated.

Endogenous Thyrotropin

With primary hypothyroidism, an increase in TSH serum concentrations would be expected because of the lack of negative feed back mechanism of the thyroid hormones on the pituitary. However, about one fourth of the dogs with hypothyroidism show TSH serum concentrations within the reference range. Because of the weak sensitivity of the TSH measurement for the diagnosis of hypothyroidism, this test cannot be recommended solely. To reliably evaluate canine thyroid function, a T4 measurement (FT4 or TT4) is always combined with a TSH measurement. A serum sample with decreased T4 and increased TSH serum concentrations (>0,6 ng/ml) will confirm with confidence the diagnosis of primary hypothyroidism. When the measurements of T4 and TSH give contradictory results, it is recommended to repeat measurements 4-8 weeks later or to perform further testing (i.e., FT4 measurement, rhTSH stimulation, scintigraphy).

Free Thyroxine (FT4)

In theory, the measurement of FT4 should reflect more precisely thyroid function. The most reliable technique used to measure FT4 involves equilibrium dialysis, only available in some laboratories and more expensive than measurement of a TT4. Free T4 serum concentrations seem less influenced by non-thyroidal illnesses than TT4. Measuring FT4 seems therefore more interesting to evaluate thyroid function, if measurement is performed after equilibrium dialysis.

Thyrotropin Stimulation Test

Canine thyroid stimulation with bovine TSH is less affected by the presence of non-systemic thyroid diseases than is a baseline TT4 measurement. Therefore the bovine TSH stimulation test has long been considered as the gold standard for thyroid evaluation in dogs. Today, the bovine TSH stimulation test is less used for several reasons: expense, 4-6 hour test, bovine TSH is difficult to obtain and FT4 and TSH measurements are available. However, in non-infrequent cases with controversial results, performing a TSH stimulation test would still be very interesting. Sauvé and Paradis showed that recombinant human TSH (rhTSH) will stimulate the thyroid gland of euthyroid beagle dogs. Major limiting factors for the use of rhTSH in dogs resided in the cost of the product and some practical aspects: one vial contains 1.1 mg of lyophilized rhTSH, while the amount needed to perform a TSH stimulation test in dogs varies from 50 to 100 µg. We showed that rhTSH can be stored in aliquots at 4°C for 4 weeks and at-20°C for 8 weeks without loss of biological activity. This allows clinicians to perform more TSH response tests per vial.

A study performed at the University of Montreal (Daminet et al., submitted), showed the ability of the rhTSH stimulation test to differentiate euthyroid dogs, dogs with hypothyroidism and euthyroid dogs with nonthyroidal illnesses.

We have used the rhTSH stimulation test in our clinic almost exclusively in dogs with ambiguous thyroid function test results, especially in dogs suspected of having hypothyroidism with decreased TT4 serum concentrations and TSH levels within the reference range, but also in dogs with TT4 values within the reference range accompanied with an increased TSH concentration.

Antibodies Against Thyroid Hormones

Anti-thyroglobulin antibodies (ATG) are found in only 36 to 60% of hypothyroid dogs. The presence of ATG in euthyroid dogs (false positives) is now only observed in less than 5% of dogs. Epidemiological analysis of the prevalence of ATG has shown considerable breed and age variation. The presence of ATG does not necessarily reflect thyroid ability to synthesise thyroid hormones. The presence of antibodies in combination with normal thyroid hormone values can be an indication that hypothyroidism might develop.

Rarely, anti-T3 and anti-T4 antibodies are observed in hypothyroid dogs. Therefore their clinical use is limited. These antibodies can however interfere with radio immunoassay determination of T3 or T4, and lead to falsely increased values as a consequence.

Medical Imaging

Scintigraphy is a very useful method for evaluation of thyroid function. When available, it can be used to differentiate dogs with the euthyroid sick syndrome from truly hypothyroid dogs.

Ultrasonographic changes observed in hypothyroid dogs were recently described and include a decrease in thyroid volume and a decreased echogenicity compared to normal dogs. Quality of the ultrasonographic equipment and experience of the ultrasonographer may negatively impact accurate measurement of thyroid size and will most likely limit the use of ultrasonography for the diagnosis of hypothyroidism in current veterinary practice.

Influences on Thyroid Function Tests

Numerous diseases and drugs can influence thyroid function. Besides this many other physiological factors such as, age, breed and fluctuating serum concentrations, can influence the results. Some dog breeds clearly have thyroid hormone concentrations lower than values observed in most breeds. For example, Greyhounds have TT4 values that are markedly lower (half) than in other breeds. Recently we investigated thyroid hormone values in Whippet dogs and also demonstrated that caution is also advised in this breed as lower TT4 values were found when compared to control dogs.

Summary of the effects of some drugs on canine thyroid function test results.

Conclusion

Treatment of hypothyroidism is relatively simple, but obtaining a reliable diagnosis can sometimes be more difficult. Numerous factors can influence thyroid homeostasis. Knowledge of these factors can contribute to decreasing the misdiagnosis of hypothyroidism. Non-thyroidal diseases and the administration of medications can lead to decreased thyroid hormone concentrations. As always, laboratory results should be interpreted in light of history and physical examination findings.

References

References are available upon request.