The ideal treatment of hyperthyroidism due to Graves disease (GD), an autoimmune disorder ultimately caused by TSH-receptor antibody, would consist of the elimination of disease triggers. Because this is not feasible, current management relies on either thyroid ablation (thyroidectomy and/or radioiodine) inevitably bound to subsequent hypothyroidism, or a conservative approach using antithyroid drug (ATD) treatment. The latter is associated with a high rate (about 4050%) of relapse of hyperthyroidism. Commonly used ATDs (thionamides) mostly act by inhibiting thyroid hormone synthesis, although (direct or indirect) immunosuppressive actions are also postulated. Two different ATD regimens are in common use for GD: i) Titration method; ii) Block-and-replace method. In the titration method, the usual starting dose is 1530 mg/day methimazole (or equivalent doses of other thionamides); further to periodic thyroid status assessment, daily dose is tapered down to the lowest effective dose (avoiding both hyper- and hypothyroidism). Thyroid function tests are checked every 46 weeks for the first 46 months, then every 34 months until treatment is stopped after 1824 months. The block-and-replace method uses persistently high ATD doses in association with L-thyroxine replacement to avoid hypothyroidism; treatment lasts 6 months. This method has advantages and disadvantages over the titration method. Higher doses of ATDs may have a greater immunosuppressive action useful for a permanent remission of hyperthyroidism, but this putative effect remains to be demonstrated. Avoidance of hypothyroidism or escape of hyperthyroidism seems easier than with the titration method; treatment is shorter, and the number of visits lower. On the other hand, the much higher number of tablets taken every day may create problems of poor compliance. The block-and-replace method should not be used during pregnancy. A recent systematic review (Abraham et al., Eur J Endocrinol 2005 153 489498) showed that the block-and-replace method has no advantages in terms of permanent remission of hyperthyroidism, while the prolonged use of high ATD doses may bear a higher risk of side effects. The latter conclusion has recently been questioned (Razvi et al., Eur J Endocrinol 2006 154 783786), but in the absence of powered controlled trials comparing the two regimens, this author feels that the titration method is preferable.
03 - 07 May 2008
European Society of Endocrinology