Similar effects of thionamide drugs and perchlorate on thyroid-stimulating immunoglobulins in Graves' disease: evidence against an immunosuppressive action of thionamide drugs

Abstract

Previous studies have shown that serum titers of thyroid-specific antibodies such as thyroid-stimulating immunoglobulins (TSI), TSH-displacing antibodies (TDA), or microsomal antibodies (MAb) decrease in patients with Graves' disease during therapy with thionamide drugs (TD). In keeping with some in vitro results it was postulated that TD have an immunosuppressive action which may be partly responsible for the beneficial effects. To further elucidate this theory, we compared the changes in TSI during treatment with TD such as methimazole (MMI) and propylthiouracil (PTU) as well as with perchlorate (PC), an unrelated compound with a different mode of therapeutic action. Of 69 patients with hyperthyroidism due to Graves' disease, serum from 62 (90%) was positive for TSI, as measured by cAMP accumulation in a thyroid tissue culture assay. Six patients had to be excluded due to noncompliance. Of the remaining 56 patients, those 41 subjects (73%) with good control of the disease were followed up to 24 months during dose-adjusted antithyroid treatment. All patients with an uncomplicated course of treatment had a decline in the initially increased TSI values on either drug regimen. Five of 10 patients receiving PTU and 8 of 13 patients receiving MMI reached normal TSI levels; so did 11 of 18 patients receiving PC. There was no individual correlation between TSI decrease and drug dosages or the serum T4 and T3 levels. In all 3 groups, however, a decrease in mean T4 and T3 levels preceded the fall in TSI. By grouping the patients according to whether they had more than a 20% decrease in the initial TSI values after either 2 months or more than 4 months of treatment, it could be shown that the late responders had significantly higher T4 and T3 levels after 2 months of treatment. The similar patterns of change in TSI during treatment with TD and PC are strong evidence against an immunosuppressive effect of TD. If any direct interference occurs, a toxic effect on intrathyroidal lymphocytes by intrathyroidal drug accumulation could be the cause of the disappearance of TSI with both drug types. On the other hand, the data provide indirect evidence for the theory that the restoration of the euthyroid state is the cause of decreasing TSI levels and normalization of the immune regulation in many patients during treatment with antithyroid drugs.