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.

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.