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.