Context: Although methimazole (MMI) and propylthiouracil (PTU) have long been used to treat hyperthyroidism caused by Graves' disease, there is still no clear conclusion about the choice of drug or appropriate initial doses.

Objective: To compare the MMI 30mg/day-treatment with the PTU 300mg/day- and MMI 15mg/day-treatment in terms of efficacy and adverse reactions.

Design, Setting and Participants: Patients newly diagnosed with Graves' disease were randomly assigned to one of the three treatment regimes in a prospective study at four Japanese hospitals.

Main outcome measurements: Percentages of patients with normal serum free T4 (FT4) or free T3 (FT3) and frequency of adverse effects were measured at 4, 8 and 12 weeks.

Results: MMI 30mg/day normalized FT4 in more patients than PTU 300mg/day and MMI 15mg/day for the whole group (240 patients) at 12 weeks (96.5% vs. 78.3%, P=0.001, and 86.2%, P=0.023, respectively). When patients were divided into two groups by initial FT4, in the group of the patients with severe hyperthyroidism (FT4: 7ng/dl or more, 64 patients) MMI 30mg/day normalized FT4 more effectively than PTU 300mg/day at 8 and 12 weeks and MMI 15mg/day at 8 week, respectively (P<0.05). No remarkable difference between the treatments was observed in patients with initial FT4 less than 7ng/dl. Adverse effects, especially mild hepatotoxicity, were higher with PTU and significantly lower with MMI 15mg/day compared with MMI 30mg/day.

Conclusion: MMI 15mg/day is suitable for mild and moderate Graves' disease, while MMI 30mg/day is advisable for severe cases. PTU is not recommended for initial use.