SHORT-TERM TREATMENT OF GRAVES-DISEASE WITH METHIMAZOLE IN HIGH VERSUS LOW-DOSES

Objectives. To compare the relapse rates in Graves' disease the first 2 years after methimazole 60 mg day(-1) combined with thyroxine versus a titration regimen with methimazole alone, and to look for possible prognostic factors. Design. A randomized, open, prospective study. Methimazole was given for 6 months in both groups, and thyroid status evaluated every 3rd month during the first year, and every 6th month during the second year. Setting. The study was performed at our outpatient clinic with patients referred from primary care. Subjects. Fifty-six patients were included. One became pregnant and one dropped out during the treatment period. Furthermore, nine patients in the high-dose and four in the low-dose group stopped the treatment because of side-effects. Thus, 19 patients in the high- and 22 in the low-dose group completed 6 months with methimazole. Results. In those tolerating the treatment, the relapse rates in the high- and low-dose groups were 26.3 vs. 59.1% (P < 0.05), 42.1 vs. 77.3% (P < 0.02); and 57.9 vs. 77.3% (NS) after 3, 12 and 24 months, respectively. The corresponding relapse rates calculated on an 'intention to treat' basis were: 51.7 vs. 66.7%; 62.1 vs. 81.5%; 72.4 vs. 81.5% (NS). The thyroid volume was significantly (P < 0.05) larger in those that relapsed (17.8 +/- 2.9 vs. 11.6 +/- 1.2 mL; mean +/- SEM). Conclusions. In those tolerating the treatment, methimazole significantly reduced the relapse rate the Ist year when given in a high dose. However, the relapse rates in both groups, and the number of side-effects in the high-dose group, were unacceptably high.