A PROSPECTIVE RANDOMIZED TRIAL OF ANTITHYROID DRUG DOSE IN GRAVES-DISEASE THERAPY

Some studies have suggested that increasing the daily dose of antithyr oid drugs might improve long-term remission rates of Graves' disease. Therefore, this question was addressed in a prospective multicenter tr ial involving 18 thyroid clinics in Europe, mostly in iodine-deficient or moderately iodine-sufficient regions. Five hundred and nine patien ts with Graves' hyperthyroidism were enrolled in a prospective randomi zed trial comparing the remission rates after treatment with methimazo le (MMI) at two fixed dosages (10 vs. 40 mg) with levothyroxine supple mentation. The treatment and follow-up periods lasted 12 months each. Sixty and seven-tenths percent of the recruited patients (total, 309; 153 in the 10 mg, 156 in the 40 mg group) were finally evaluated, and comparison of the two groups showed that they were well matched with r espect to a wide range of variables, including parameters of thyroid f unction. With 10 mg MMI daily, 68.4% of the patients were euthyroid af ter 3 weeks, and 84.9% after 6 weeks, compared to 83.1% and 91.6%, res pectively, with the use of 40 mg MMI daily. TSH receptor antibodies de creased similarly in the two groups, 25% of patients in the 10 mg grou p, and 30% in the 40 mg group still being TSH receptor antibodies posi tive after 12 months. One hundred and ninety six (63.4%) of the 309 pa tients achieved remission of Graves' disease. The two MMI doses were e qually effective; 35.9% compared to 37.2% of patients treated with 10 and 40 mg MMI, respectively, had relapses. There was no difference in the length of the time interval between stopping treatment and recurre nce between the two groups. However, the rate of adverse drug reaction s increased from 39/251 (15.5%) in the 10 mg group to 67/258 (26.0%) i n the 40 mg group (P < 0.01). Under conditions of iodine deficiency or borderline sufficient iodine supply, 40 mg MMI daily will render more patients with Graves' disease euthyroid within the first 6 weeks of t reatment than 10 mg daily, but at the expense of an increased rate of adverse reactions. However, patients treated with 40 mg MMI daily for 1 yr have no higher chance of remission than patients treated with 10 mg. It does not appear justified at present to recommend MMI doses hig her than required for the control of hyperthyroidism (with the goal of immunosuppression).