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Graves' disease may result eventually in hypothyroidism in approximately 5-20% of patients. In a few such patients hypothyroidism was associated with TSH-blocking antibodies, but whether the frequency of TSH-blocking antibodies in such patients is as high as it is (21%) in patients with primary myxedema is not known. This study was undertaken to determine the presence of various immunoglobulins [TSH binding inhibitor immunoglobulins, thyroid-stimulating antibodies (TSAb), and TSH-blocking antibodies] in 26 patients with Graves' disease who developed hypothyroidism from 0.5-10 yr or more after discontinuation of antithyroid drug therapy. Eight of the 26 patients (31%) had TSH-blocking antibodies, 16 (61%) had TSAb, and 14 (54%) had thyroid hormone binding inhibitor immunoglobulins. Thyroid needle biopsies were performed in 9 patients. Three of 5 patients who had subclinical hypothyroidism had chronic lymphocytic thyroiditis, and all had positive TSAb titers. Three patients had the fibrous variant of chronic lymphocytic thyroiditis; their TSAb values were 902%, 431%, and 1290%. One patient had follicular hyperplasia. We conclude that TSH-blocking antibodies may account for hypothyroidism in approximately one third of patients with Graves' disease who were previously treated with antithyroid drugs, and that autoimmune thyroiditis is comparable for the hypothyroidism in the remaining two thirds of Graves' disease patients.

The presence of serum antithyroglobulin (TGHA) and antithyroidal microsomal (MCHA) antibodies in Graves' disease patients is associated with lymphocytic infiltration of the thyroid. The aim of this study was to determine the clinical significance of TGHA and MCHA during and after treatment of hyperthyroidism due to Graves' disease. One hundred and seventeen such patients were treated for 2 yr with methimazole and then followed for an additional year or more (mean, 30 months). The patients were classified into the following three groups: group I, patients negative for TGHA and MCHA before and during the 2 yr of treatment; group II, patients positive for MCHA but negative for TGHA before and during the 2 yr of treatment; and group III, patients who were positive for both TGHA and MCHA before and during treatment. The relapse rates after discontinuation of treatment in these groups were 39% (13 of 33), 27% (13 of 48), and 11% (4 of 36), respectively; the value in group I was significantly higher than that in group III (P less than 0.01). The results suggest that the presence of TGHA and MCHA may influence the prognosis of Graves' disease in patients treated with methimazole. Those patients who had neither antibody before and during treatment were most likely to have a relapse of hyperthyroidism, and those who had both antibodies were least likely to have a relapse.

We reviewed the records of approximately 7000 Japanese patients whose hyperthyroidism was treated with methimazole (MMI) alone. Four patients (Group I) developed agranulocytosis during a second course of MMI therapy and eight patients (Group II) during an initial course. Six patients (three in each group) received less than 30 mg MMI daily. Agranulocytosis occurred after more than 2 months of therapy (12 weeks-1 year) in five patients. Seven patients were less than 40 years of age. One patient displayed a gradual protracted development of agranulocytosis. These results indicate that agranulocytosis after MMI may occur irrespective of dose, age, duration of treatment, and with a second exposure.