Serum thyrotropin-receptor autoantibodies levels after 131I therapy in Graves' patients:: effect of pretreatment with methimazole evaluated by a prospective, randomized study

Objective: Radioiodine therapy (I-131) in hyperthyroid Graves' disease is generally followed by a transitory increase in levels of thyrotropin receptors antibodies (TRAb). Immunosuppressive effects of antithyroid drugs are still a matter of debate. In this study we evaluated the effect of methimazole pretreatment on the TRAb boost induced by I-131. Design: A randomized, prospective clinical trial. Methods: 61 patients were randomly assigned to receive I-131 alone (32 patients) or I-131 plus pretreatment with methimazole (30 mg/day; 29 patients). Serum TRAb levels were measured on the day of I-131 dosing (DO), and at 1, 3, 6 and 12 months after I-131 administration. Results: The mean serum TRAb levels decreased significantly from baseline to DO in patients treated with methimazole (80.8 vs 48.8 U/I; P < 0.05). After I-131 treatment, TRAb levels increased at 3 months (48.8 to 60U/I; 19%) and they were still elevated at 6 months compared with DO values (99.9 U/I; 105%). Thereafter, TRAb levels decreased to baseline values (47.8 U/I) at 12 months. In hyperthyroid patients, TRAb levels increased significantly from DO to 1. month (45.0 to 78 U/I; 73%) reaching their highest levels at 3 months (225 U/I; 400%). After this, we observed a progressive decrease to the baseline levels at 12 months (40.0 U/I). The course of TRAb levels after I-131 treatment was significantly different between the two groups (P < 0.05). Multiple regression analysis identified serum TRAb levels on DO as independent predictors of TRAb increment after I-131 therapy (r 2 = 0.34; P = 0.001). A higher increment in serum TRAb levels was associated with hypothyroidism after 1 year of follow-up. Conclusion: Methimazole pretreatment attenuates the I-131-induced rise in serum TRAb levels. The effects of methimazole could be attributed to a direct immunomodulatory action or may be due to its effects on the control of hyperthyroidism, which is a known cause of immune dysregulation.