EVIDENCE FOR CARBIMAZOLE AS AN ANTIOXIDANT

There is evidence in the literature to support the view that antioxida nts are involved in the pathogenesis of Graves disease and that antiox idants may act as free radical scavengers. This study has compared the effects of a 12 month course of conventional Carbimazole therapy on p eripheral blood antioxidant levels with those of a 12 month course of a higher dose treatment regime. Fifty seven patients were enrolled int o the study. Those in Group 1 (n = 23) received a 12 month course of 6 0 mg/day Carbimazole. Those in Group 2 (n = 34) received 45 mg/day for the first month, 30 mg/day for the second and 20 mg/day for the remai ning 10 months of treatment. T3 was added in both groups after 2-4 mon ths to maintain patients euthyroid. Baseline samples were also obtaine d from 30 control subjects. Blood samples were taken for the measureme nt of plasma thiol (PSH), lysate thiol (LSH), superoxide dismutase (SO D) and caeruloplasmin (CP) and for routine thyroid function tests (TT4 , TT3 and TSH). in untreated Graves' patients, serum levels of PSH and SOD were reduced and levels of LSH increased compared to controls. Fo llowing 2 months high dose Carbimazole therapy there was a significant increase in PSH levels and a significant reduction in CP levels compa red to presentation levels. In the more conventional dose Group 2 pati ents PSH levels also rose significantly during the first 2 months of t reatment. Levels for both groups were still significantly lower than t he control group. After 12 months high dose Carbimazole therapy PSH le vels had decreased so that they no longer differed from untreated leve ls. LSH and SOD levels still remained abnormal. CP levels continued to fall. Similar findings were obtained in those patients receiving the more conventional course of treatment. At no point n;as their any sign ificant difference in antioxidant levels between the two treatment gro ups. The abnormal levels of antioxidants in the serum of untreated Gra ves' patients confirm their involvement in the pathogenesis of Graves' disease. Carbimazole therapy appeared to have only short term effects on the peripheral blood levels of the antioxidants measured. Carbimaz ole appeared to act only on the extra cellular markers of antioxidant activity (PSH, CP) although the disease itself had marked intracellula r effects (LSH, SOD). These findings suggest that Carbimazole does not act as a free radical scavenger.