Clinical Trial of Four Weeks of Combination Therapy with Low-dose Methimazole and a Cholesterol Absorption Inhibitor as the Initial Treatment for Childhood-onset Graves’ Disease

The initial treatment of childhood-onset Graves' disease is based on the result of clinical trials of adult-onset disease. The major adverse events associated with methimazole, the only medication approved for childhood-onset disease in Japan, are considered to depend on the dose, and the risk of adverse events is increased in patients requiring higher doses for initial treatment. The serum levels of thyroid hormones are partially dependent on the enterohepatic circulation, especially under thyrotoxicosis. Cholesterol absorption inhibitors suppressing the enterohepatic circulation have the possibility of controlling thyrotoxicosis. In this clinical trial, 13 patients with childhood-onset Graves' disease (5.5 to 15.3 yr old) were divided into three treatment groups: low-dose (0.25 mg/kg/d) methimazole monotherapy, high-dose (1.0 mg/kg/d) methimazole monotherapy, and combination (low-dose methimazole + a cholesterol absorption inhibitor) therapy. The therapeutic efficacy was determined based on the rates of decrease of thyroid hormones for four weeks. The high-dose methimazole regimen was superior in efficacy to the low-dose methimazole regimen, while the combination therapy demonstrated effects equal to those of the high-dose monotherapy. Therefore, combination therapy with a cholesterol absorption inhibitor can improve thyrotoxicosis, and the dose of methimazole can be reduced in the initial treatment of child-onset Graves' disease.