Reevaluation Of The Effects Of Methimazole And Propylthiouracil In Patients With Graves' Hyperthyrodism

Objective: The present study is intended to assess the efficacy of different doses of methimazole (MMI) and propylthiouracil (PTU) in the treatment of Graves'hyperthyroidism.Background: Antithyroid drugs, MMI and PTU, are widely used in the treatment of hyperthyroidism. The plasma half-life of PTU is only 1-2h and its antithyroid function maintains less than 24h. So it has to be dosed three times a day. The plasma half-life of MMI is 4-6h. In order to maintain the therapeutical plasma concentration, it was thought that it should be dosed three times a day. However, the plasma concentration and half-life of MMI don't represent the intrathyroid concentration and half-life of MMI. Studies indicate that the intrathyroid half-life of MMI is longer than that in plasma and it lasts at least 20-24h, while the antithyroid efficacy arises from intrathyroid concentration of MMI【10】. The research by Huang and his colleagues【21】indicates that the thyroid gland regulates the intake of MMI and it can reach saturation. A single daily dose of 15mg MMI is the dosage where the thyroid concentration of MMI reaches saturation. Previous studies【20】【11】【31】demonstrate that a single daily dose of 15mg MMI has the efficacy of blocking thyroid iodide organification of 76.5% for up to 24h and reducing the TPO activity to 8.42±4.34GU/g tissue. It has superior results in turning positive TRAb into negative to mulitple doses of MMI and PTU. It has been reported that【17】a single daily dose of 15mg MMI is much more effective in lowering thyroid hormone and TRAb levels than a single daily doses of 150mg PTU. However, there has not been any prospectively randomized study to evaluate the effects of 15mg MMI once a day or 50mg PTU three times a day in lowering the thyroid hormone and TRAb level of Graves'hyperthyroidism. The focus of the present study is to investigate the above-mentioned issues. Though some research shows that the traditional dosage of MMI treatment is superior to PTU treatment in lowering the thyroid hormone level, it doesn't evaluate the effects on immunology. This is included in the present study.Methods: Our patients were randomly recruited from outpatient clinics at First Hospital of Shanxi Medical University. Totally 60 patients with newly diagnosed mild and moderate Graves'hyperthyroidism were recruited. The 60 patients were randomly divided into four groups with 15 cases in each group. Two groups were dosed with small doses of ATD where one group randomly took MMI 15mg once a day and the other group took PTU 50mg three times a day for 12 weeks. The other two groups were dosed with traditional doses of ATD where one group randomly took MMI 10mg three times a day and the other group randomly took PTU 100mg three times a day for 12 weeks. The therapeutic efficacy was determined biochemically by thyroid function tests (FT3, FT4 and sTSH) and TRAb activity before and at the end of 4, 8 and...