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Effect of Methimazole, with or without L-Thyroxine, on Remission Rates in Graves’ Disease¹

Division of Endocrinology and Metabolism, Department of Medicine, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada B3H 2Y9

Address all correspondence and requests for reprints to: Roger S. Rittmaster, M.D., Room 2035D, Victoria Building, QEII Health Sciences Centre, 1278 Tower Road, Halifax, Nova Scotia, Canada B³H 2Y9.

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 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.

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