Failure of Thyroxine Therapy for Graves Disease

TO THE EDITOR: More than 4 years ago, Hashizume and colleagues [1] reported a new medical treatment for Graves disease that was associated with an astonishingly low relapse rate. In this study, 60 hyperthyroid patients were rendered euthyroid with methimazole and then treated for 1 year with both methimazole, 10 mg/d, and thyroxine, 100 g/d, followed by thyroxine alone for 3 more years. Only 1 of these 60 patients (1.7%) became hyperthyroid during the 4-year study period, compared with 17 of 49 patients (34.7%) in a control group receiving placebo instead of thyroxine. To explain this dramatic result, the researchers suggested that thyroxine may suppress thyroid autoimmunity by several different mechanisms. Since 1991, we have used Hashizume and colleagues' protocol to treat six patients with Graves disease in the endocrine clinic of a large public hospital. The patients were selected for long-term medical therapy because they had refused radioiodine treatment. Their hyperthyroidism ranged from mild to severe. The characteristics of these patients and the results of treatment are given in Table 1. Although our sample is small, we have had more failures in the treatment of six hyperthyroid patients using thyroxine than Hashizume and coworkers had in more than 100 patients in two separate studies [1, 2]. Two of our patients had relapse while receiving the fixed-dose initial regimen of methimazole and thyroxine, and three patients subsequently had relapse while receiving thyroxine alone. Our poor results probably cannot be explained by noncompliance, given that all patients had become euthyroid while receiving antithyroid drugs before beginning the protocol. Genetic, geographic, or dietary differences may account for the disparate results. Our discouraging observations and those of others [3-5] question the effectiveness of thyroxine for treating Graves disease. Table 1. Characteristics of Six Patients Receiving Methimazole and Thyroxine for the Treatment of Graves Disease