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.