Predictors of outcome and comparison of different drug regimens for the prevention of relapse in patients with Graves' disease

Division of Endocrinology, Department of Internal Medicine, University of Bergen, Bergen, Norway. bjorn.nedrebo@ikb.uib.no

OBJECTIVE: To investigate the effect of different antithyroid drug (ATD) regimens on relapse rates of Graves' disease, and to look for predictors of relapse. DESIGN AND METHODS: In a prospective two-way factorial randomized clinical trial, 218 patients with Graves' disease were assigned to ATD combined with l-thyroxine (l-T(4)) or ATD alone for 12 Months. After discontinuation of antithyroid therapy, each group was stratified to either 12 Months further treatment with l-T(4) or no treatment. Clinical and biochemical assessments were carried out before treatment, after 3 and 6 weeks, and every third Month for 12 Months. If the patients lacked symptoms of relapse, laboratory tests were performed every third Month for the second Year, and thereafter annually. RESULTS: The proportion of all patients with relapse was 47.7% 2 Years after withdrawal of ATD. There was no difference in relapse rates between the treatment groups (P=0.217, log--rank test). Smokers had a higher relapse rate than non-smokers (58.4% vs 38.8%, P=0.009). Patients who were thyrotropin-receptor antibody (TRAb) positive after 12 Months of antithyroid therapy had a higher relapse rate than those who were negative (72.5% vs 36.8%, P<0.0001). Similarly, relapse was more frequent (55.5%) in patients having large goiter compared with subjects with small goiter (36.3%, P=0.0007). CONCLUSIONS: Relapse rates of Graves' disease were independent of ATD regimen whether followed by l-T(4) therapy or not. Smoking, large goiter and presence of TRAb at the end of ATD therapy were strong predictors of relapse.

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