By: W. Jean Dodds, D.V.M.
Although thyroid dysfunction is the most frequently recognized endocrine disorder of the dog, a definitive diagnosis may be difficult to establish. Clinical signs of thyroid dysfunction mimic symptoms resulting from other causes and interpretation of results of thyroid function tests can be problematical. Most canine thyroid disease is the result of autoimmune thyroiditis, which is a familial disorder of inherited predisposition similar to human Hashimoto’s disease. Therefore, the most complete approach to thyroid testing should include assays for thyroid autoantibodies.
1. Baseline Thyroid Profiles
Because of the difficulties inherent to diagnosing thyroid disease, a complete baseline thyroid panel is advisable and should include measurements of total T4, total T3, free T4, free T3, and circulating T4 and T3 autoantibodies. This type of profile can be applied not only to clinical patients suspected of having thyroid disease, but also can be used for genetic screening of apparently healthy relatives to evaluate their fitness for breeding. A bitch with circulating antithyroid antibodies can pass these along to the puppies transplacentally as well as via the colostrum. Furthermore, dogs with circulating antithyroid autoantibodies may eventually develop clinical symptoms of thyroid disease and/or be susceptible to other autoimmune diseases. Thyroid prescreening is thus very important for selecting potential breeding stock.
2. Genetic Screening for Thyroid Disease
Thyroid testing for genetic screening purposes is less likely to be meaningful before puberty. Screening is initiated, therefore, once healthy dogs and bitches have reached sexual maturity (between 10 to 14 months in males and during the first anestrous period for females following their maiden heat). As the female sexual cycle is quiescent during anestrus, any influence of sex hormones on baseline thyroid function will be avoided.
This period generally begins 12 weeks from the onset of the previous heat and lasts one month or longer. The interpretation of results from baseline thyroid profiles in intact females will be more reliable when they are tested in anestrus. Once the initial thyroid profile is obtained, dogs and bitches should be rechecked on an annual basis to assess their thyroid function and overall health. This allows for early treatment, where indicated, to avoid the appearance or advancement of clinical signs associated with hypothyroidism.
For optimal health, young dogs under 15 to 18 months of age should have thyroid baseline levels in the middle to upper half of adult normal ranges. This is because puppies and adolescent dogs are still growing and maturing. Similarly, in older animals above 8 or 9 years of age, body functions slow down so that baseline thyroid levels may be in the lower third of the range in euthyroid individuals. For healthy young adults used for performance or breeding, optimum thyroid function should be at least at the mid-point of the laboratory normal ranges. Lower levels may be indicative of the early stages of thyroiditis among relatives of dog families previously documented to have thyroid disease.
3. Diagnosing Difficult or Equivocal Cases
Some dogs with typical clinical signs of hypothyroidism have circulating levels of thyroid hormones within the normal range. Most of these patients will improve clinically when given thyroid medication, because blood levels of thyroid hormones may not reflect cellular and tissue thyroid levels. A 6 to 8 week clinical trial of thyroid supplementation given twice daily is safe and appropriate for such patients, and is followed by rechecking the complete thyroid profile 4 to 6 hours after the morning pill. Response to thyroid therapy is considered an appropriate justification for continuing to prescribe thyroid hormone. The usual therapeutic dosage is 0.1 mg (100 ug) per 4.5 Kg (10 lbs.) BID.
Once the appropriate dose of thyroid supplement is established, annual retesting is recommended unless the dog exhibits any sign of illness in the intervening period.
If an animal is receiving thyroid supplementation and the original diagnosis is questioned, the clinician may wish to reevaluate the patient. Whenever thyroid therapy is discontinued, retesting is performed after 4 or preferably 6 weeks, because it takes at least a month for the animal’s own pituitary-thyroid axis to be restored to full capacity.
4. Therapeutic Approaches for Refractory Cases or Those with Circulating Thyroid Autoantibodies
a. Use of T3 Supplement
When clinical signs of thyroid disease are only partially or poorly ameliorated by supplementation with L-thyroxine at standard dosages [0.1 mg per 4.5 Kg BID], combination therapy is often successful. In such cases, the T4 supplement may be poorly converted to T3 by the liver and other tissues, so that addition of a T3 supplement or a source of natural thyroid containing both T3 and T4 is indicated. The typical treatment regimen includes the full dosage of T4 supplement given twice daily plus 1 ug per 0.5 Kg (1 lb.) of T3 supplement given two or three times daily. This combination has been particularly benificial for patients with concomitant liver disease or dysfunction, because the liver is the primary site of conversion of T4 to T3. The approach also applies to patients on anticonvulsant therapy for seizure disorder. Providing this low dosage of T3 supplement enhances levels of T3 in the central nervous system to assist in raising the seizure threshold. The dosage of anticonvulsant required for seizure control may be able to bel lowered or even discontinued. It may also offset any adverse effects of anticonvulsants on liver metabolism which could impair hepatocellular conversion of T4 to T3.
b. Reversal of Thyroid Autoantibodies
For patients with circulating T4 and/or T3 autoantibodies, even in the absence of typical clinical signs of thyroid disease, thyroidsupplementation is used to interrupt the progression of thyroiditis and reverse the stimulus for production of thyroid autoantibodies. Experience with over 70 cases followed periodically up to 4 years indicates that it usually takes between 5 to 7 months of thyroid replacement for circulating thyroid autoantibodies to wane progressively and disappear. The breeds most commonly exhibiting this pattern of autoimmune thyroiditis are Golden Retrievers, Shetland Sheepdogs, Old English Sheepdogs, and Doberman Pinschers, although many other breeds are also affected. The most prevalent circulating thyroid autoantibody is against T3, followed by a combination of T3 and T4 autoantibodies. In a few instances, the patients demonstrate only T4 autoantibodies. As would be expected, these patients also have elevated levels of antithyroglobulin antibodies.
Supplementation with L-thyroxine is believed to reverse the production of circulating thyroid autoantibodies by either inducing immune tolerance and/or by negative feedback inhibition of thyroid stimulating hormone and its effects on the thyroid stimulating hormone receptor. In a typical case, the standard therapeutic dose of L-thyroxine is given for 8 to 12 weeks and then the complete baseline thyroid profile is performed to determine whether levels of circulating thyroid autoantibodies are waning. Retesting prior to this time is unnecessary because the presence of circulating autoantibodies interferes with accurate measurement of T3 and/or T4. For cases in which clinical signs of pruritic skin disease are present along with high levels of circulating thyroid autoantibodies, addition of corticosteroids for 4 to 6 weeks may be helpful. Steroid dosages begin at 1 mg per Kg divided BID for the first week and are tapered gradually to conclude with low dose every other day therapy. Thyroid therapy is usually required for life with annual rechecks.
5. Other Factors Influencing Thyroid Metabolism
Because animals with autoimmune thyroid disease have generalized metabolic imbalance and may have associated immunological dysfunction, it is advisable to minimize their exposures to unnecessary drugs, chemicals and toxins, and to optimize their nutritional status with healthy balanced diets. Recent studies have implicated selenium deficiency and potentiated sulfonamides as contributors to thyroid dysfunction or imbalance. Challenging the immune system of these animals with multivalent modified-live vaccines also has been associated with adverse effects. General recommendations are to use killed vaccine products, when these are available; space vaccines at least 10 days to 2 weeks apart to avoid excessive antigenic challenge; and perform serum antibody titration as an alternative to booster vaccination of adults in order to assess the adequacy of existing protection.