A RANDOMIZED TRIAL OF SHORT-TERM TREATMENT OF GRAVES-DISEASE WITH HIGH-DOSE CARBIMAZOLE PLUS THYROXINE VERSUS LOW-DOSE CARBIMAZOLE

OBJECTIVE The optimal treatment regimen with thionamide drugs remains a matter for debate, We have investigated whether high doses of carbim azole, when compared with low doses, reduce relapse rates of Graves' d isease. DESIGN In an open label, randomized, prospective trial of trea tment of Graves' disease we compared high doses of carbimazole (6 mont hs of 100 mg carbimazole per day plus thyroxine) to low-dose carbimazo le treatment (starting at 25 mg and titrating the carbimazole dose wit h the aim to maintain serum thyroid function test results within the n ormal reference range), PATIENTS Thirty-seven patients with a first ep isode of Graves' disease were enrolled. MEASUREMENTS During the 6 mont hs of treatment we evaluated the rate of normalization of serum thyroi d function tests, changes in serum thyroid auto-antibody levels and th e rate of side-effects during treatment, After completion of the 6-mon th treatment course patients were observed for 2 years for evidence of relapse of Graves' disease, RESULTS There were no differences between the two groups either in the rate of normalization of serum thyroid f unction tests or in serum thyroid auto-antibody levels during treatmen t, Of the 17 patients randomized to high-dose treatment seven suffered treatment side-effects, compared to only one of the 20 patients recei ving low-dose treatment (P<0.006). There was no significant difference in 2-year posttreatment remission rates on an intention-to-treat basi s between the two treatment groups (18.7% vs, 5.9%, P= NS). However, f or those patients who completed 6 months of treatment thigh-dose group =9, low-dose group=16), multivariate survival analysis demonstrated a significantly longer median relapse-free interval (P<0.04) in the high -dose group (27 weeks; 25th percentile: 9.6 weeks, 75th percentile: 75 weeks) versus the low-dose group (6 weeks; 25th percentile: 4.8 weeks , 75th percentile: 13.1 weeks). CONCLUSIONS High-dose carbimazole trea tment delays, but does not prevent, relapse from Graves' disease in th ose patients able to tolerate the treatment, However, it leads to more frequent side-effects than conventional dose treatment.