People who have Graves' hyperthyroidism have thyroid glands which are releasing too much thyroid hormone. This can cause goitres (swelling in the neck around the thyroid gland), sweating, bowel or menstrual problems, and other, especially eye symptoms (ophthalmopathy). Treatments include anti-thyroid drugs, surgery or radiation to reduce thyroid tissue. There are several choices to be made when considering the drug treatment of Graves' hyperthyroidism including the choice of drug, dose, duration of therapy, addition of thyroid hormone (thyroxine) and when to discontinue therapy. The antithyroid drugs which were used in the included randomised controlled trials (RCTs) comprised carbimazole, propylthiouracil and methimazole.
Twenty-six RCTs involving 3388 participants were identified. The majority of participants in all the studies were female (83% in the studies reporting sex distribution). The mean age was 40 years. The duration of follow up was between two to five years in eleven trials. In high dose ('block-replace') versus low dose ('titration') studies the duration of therapy was six months in two studies, 18 months in four studies and 12 months in the remaining trials.
The main outcome was the relapse rate of hyperthyroidism over one year after completion of drug treatment and this was the primary outcome in all the studies assessed. There were no deaths reported in any of the studies. None of the studies detailed incidence of hypothyroidism, changes in weight during the course of therapy, health-related quality of life, ophthalmopathy progression or economic outcomes. The evidence (based on four studies) suggests that the optimal duration of antithyroid drug therapy for the low dose regimen is 12 to 18 months. The low dose regimen had fewer adverse effects than the high dose regimen and was no less effective in trials (based on 12 trials) of equal duration. Continued thyroxine treatment following initial antithyroid therapy does not appear to provide any benefit in terms of recurrence of hyperthyroidism. Studies using immunosuppressive agents need further validation of safety and efficacy in controlled trials among different populations.
Data regarding side effects and number of participants withdrawn from therapy due to side effects were available in seven studies. The number of participants reporting rashes was significantly higher in the high versus low dose group (10% versus 6%). The number of participants withdrawing due to side effects were also significantly higher in the high versus low dose group (16% versus 9%).