Effect of methimazole, with or without L-thyroxine, on remission rates in Graves' disease

Medical treatment of Graves' disease involves antithyroid drugs with or without the addition of exogenous T4. There have been conflicting reports as to whether the addition of T4 improves remission rates or delays relapse. To evaluate this issue in a North American population, 199 patients were treated with methimazole until they were euthyroid. They were then randomized to either methimazole alone in a dose sufficient to normalize TSH (group 1), or to 30 mg methimazole daily plus sufficient T4 to maintain TSH in the upper normal range (group 2), or to 30 mg methimazole daily plus sufficient T4 to suppress TSH below 0.6 mIU/L (group 3). After 18 months, methimazole was stopped, and T4 was continued in groups 2 and 3. Because not all patients in groups 2 and 3 achieved their target TSH concentration, they were reassigned to group A (TSH > or = 1.0) or group B (TSH < 1.0), based on the mean TSH achieved during methimazole treatment. One hundred forty-nine patients have been followed for at least 6 months after stopping methimazole (mean 27 months). Fifty-eight percent of patients have relapsed. There were no significant differences in relapse rates after stopping methimazole. Among those patients who did relapse, however, there was a significant difference in the months to relapse after stopping methimazole between groups B and 1 (group 1: 3.3 +/- 0.7, group A: 5.6 +/- 0.8, group B: 7.4 +/- 1.7; P = 0.01 for the comparison between groups B and 1). We conclude that the addition of T4 to methimazole does not improve long-term remission rates in Graves' disease.