Burch and colleagues have provided data on individual patients showing that changes in thyroid function after discontinuation of antithyroid drug therapy are unrelated to the thyroid hormone levels present when therapy was discontinued (which the authors previously had ambiguously termed "basal levels"). The data support my contention that patients who are rendered euthyroid by antithyroid agents are unlikely to develop significant hyperthyroidism when the drugs are withdrawn. Only 1 of 17 patients had a dramatic increase in free thyroxine levels, and most patients had less than a twofold increase. It was also reassuring to note that in the authors' original report [1], a negative correlation was observed between patient age and the change in triiodothyronine values, suggesting that the elderly are less likely to have dramatic increases in triiodothyronine levels after antithyroid drug therapy is discontinued.

I stand by my original statement about the controls. The four patients who did not receive antithyroid drug pretreatment were directly compared with the patients treated with antithyroid drugs regarding changes in hormone levels after administration of Iodine-131, that is, they were used as a comparison group. The authors also noted "rapid decreases" in thyroid hormone levels after Iodine-131 administration in this untreated group. This finding might lead some to conclude erroneously that this phenomenon, observed in only four patients, was representative of a larger cohort of patients not pretreated with antithyroid agents.

My "alternative to conventional approaches" was not based on the data of Burch and colleagues as they suggest but rather on knowledge of antithyroid drug pharmacology. Whereas older data suggested that the duration of action of methimazole might be as long as 60 hours, more recent studies have indicated that the action duration of methimazole is no more than 1 or 2 days [2]. Even Burch and associates would admit that the action duration of propylthiouracil is no longer than 1 day. Therefore, I maintain that antithyroid drugs do not need to be stopped for more than 2 or 3 days before Iodine-131 therapy. I believe that the concern about reduced therapeutic benefit from Iodine-131 is not legitimate, given that an increase in the Iodine-131 dose should compensate for any loss of therapeutic efficacy.

Does pretreatment with antithyroid drugs do any harm? I am the first to admit that antithyroid agents are potentially harmful. I have heard reports of several young, otherwise healthy patients who developed agranulocytosis when routinely pretreated with antithyroid drugs before Iodine-131 administration. Thus, I do not concur with those who recommend antithyroid drug pretreatment for all patients. On the other hand, the reports of thyrotoxicosis exacerbations after Iodine-131 administration (with and without antithyroid drug pretreatment) are too numerous to mention. I challenge Burch and colleagues to find a single case in which an exacerbation of thyrotoxicosis or thyroid storm followed Iodine-131 when the patient had documented normalization of thyroid function before Iodine-131 administration.

I concur with Burch and associates that this question deserves further study. I believe that the risk–benefit ratio favors antithyroid drug pretreatment in the elderly, especially in those older patients with toxic multinodular goiter; in patients with severe longstanding hyperthyroidism; and in patients with coronary artery disease, congestive heart failure, or atrial fibrillation.