Hypothyroidism is the most common endocrine disorder in dogs, but it is also the most over diagnosed. 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. Several clinical cases will be presented throughout the presentation and emphasis will be placed on some new developments.

Physiology of the hypothalamic-pituitary-thyroid (HPT) axis

Clinically relevant physiology will be briefly reviewed.

Etiology of canine hypothyroidism

Although dysfunction anywhere in the hypothalamic-pituitary-thyroidal axis may result in thyroid hormone deficiency, more than 95 % of clinical cases of hypothyroidism in dogs result from destruction of the thyroid gland itself (i.e., primary hypothyroidism). The 2 most common causes of adult-onset primary hypothyroidism in dogs are lymphocytic thyroiditis and idiopathic atrophy of the thyroid gland, each accounting for about one-half of the cases of hypothyroidism. Congenital hypothyroidism (most often central) is rare compared to acquired hypothyroidism.

Clinical signs of hypothyroidism in dogs

Thyroid hormones have an effect on all levels of metabolism and their deficiency can lead to dysfunction of several organs. Clinical signs of hypothyroidism are vague and insidious in onset. Furthermore, many diseases, such as canine recurrent flank alopecia (CRFA) or any systemic condition can lead to clinical signs suggestive of hypothyroidism. This disease is most commonly observed in middle sized to large breed dogs and occurs preferably between 3 and 8 years of age. A few breeds, such as the Doberman, Golden Retriever, de Irish Setter, Airedale Terrier, Great Dane, Bobtail and Beagle seem predisposed. Primary acquired hypothyroidism is infrequent under the age of 2 years.

Summary of the most common clinical signs observed in dogs with hypothyroidism

Non-specific laboratory changes observed in canine hypothyroidism

Finding a hypercholesterolemia (75% of the cases) and a nonregenerative anemia (30% of the cases) on a blood analysis can increase the suspicion for hypothyroidism. The packed cell volume typically remains above 25%. Unfortunately, these changes are not specific for hypothyroidism.

The specific thyroid tests used in dogs will be discussed in the next conference. However, during case presentation some data about the use of rhTSH (recombinant human TSH) to perform TSH stimulation tests will be presented.

Influence on thyroid function tests

Numerous diseases and medications can influence thyroid function. Besides this many other physiological factors such as, age, breed and fluctuating serum concentrations, can influence the results.

A. Physiological influences

Thyroid hormone concentrations vary opposite to age. Half of the dogs older then 6 years of age have lower TT4 serum values. Thyrotropin stimulation test results are also less pronounced in older dogs.

Greyhounds have TT4 values that are clearly lower (half) than in other breeds. Thyroid function test results in this breed should therefore be interpreted very cautiously.

Globally, there are no differences in thyroid hormone concentrations between male and female dogs. But, pregnant bitches or bitches in dioestrus (progesterone influence) have TT4 serum concentrations that are higher then a non-selected population.

Daily random fluctuations in thyroid hormone concentrations have been described in euthyroid dogs. Recently we evaluated thyroid function in dogs with obesity and in dogs undergoing a weight loss protocol. TT3 and TT4 were higher in obese dogs as compared to lean dogs. Weight loss resulted in a significant decrease in TT3 and TSH concentrations. However, the observed changes are unlikely to affect interpretation of thyroid function test results in clinics.

B. Effects of drugs on canine thyroid function

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

C. Systemic non-thyroid diseases

The presence of a systemic non-thyroidal disease, such as diabetes mellitus, liver disease, hyperadrenocorticism and renal-or hart failure, is a frequent cause for decreased thyroid hormone concentrations. This phenomenon is referred to as the "euthyroid sick syndrome". These changes probably reflect a physiological adaptation of the organism leading to a decrease in tissue energy requirements. The administration of synthetic thyroid hormones to these patients is not recommended.

Treatment of canine hypothyroidism

Treatment of hypothyroidism consists in life long administration of synthetic levothyroxine (L-T4). Dosages used to treat dogs are higher then in human medicine. Initial treatment dosages varies from 11 to 22 µg/kg q 12 hour according to the author, with a maximum of 0,8 mg of Lthyroxine q 12 hour. The patient is revaluated 1 to 2 months after initiating therapy and dosage is adjusted based on clinical response, and results of the TT4. The pharmacokinetics of levothyroxine after oral administration varies from patient to patient, therefore an individual adjustment of the dosage is needed. After some time, in most dogs, once daily administration will be sufficient. Successful therapy is first of all assessed by a good clinical examination. Lethargy should resolve within 2 weeks of initiating therapy. Hair regrowth will be more progressive, but an improvement should be noticed within 4-6 weeks. Blood abnormalities should be normalised within 4-6 weeks. The nonresolution of the clinical signs within 6-8 weeks can have several origins such as; poor owner's compliance with treatment, the dosage used is not optimal, diagnosis could be wrong or an additional disease could be present. Most commonly treatment is evaluated through measurement of TT4. When interpreting the result of TT4, time of sampling compared to the administration of the medication, should be taken into consideration. When blood sample is taken just before administration of the medication (pre-tablet test), nadir concentrations are measured. Most commonly blood is taken 4 to 6 hours after the last medication is administered (posttablet test) and peak concentrations are measured. In this case, TT4 is expected to be within the reference range (upper half limit), but a TT4 value just above the reference range is accepted. Free T4 can also be used to assess therapy. The recommendations concerning time of sampling and interpretation of results are similar as for TT4.

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.