Treatment of amiodarone-induced thyrotoxicosis has been recognized as a disturbing medical problem because the response to conventional medical therapy is frequently disappointing [1]. Nevertheless, it seems that incomplete knowledge of the pathogenesis of amiodarone-induced thyrotoxicosis may have contributed to inadequate treatment schedules and the varied responses reported. Two mechanisms are actually accepted [2, 3].

In type I, exposure of a latent autonomously functioning thyroid to iodide (nodular goiter, Graves disease) results in increased hormone synthesis. Patients present with underlying thyroid abnormalities on physical and echographic examination; diminished, normal, or increased radioactive iodine uptake; and slightly elevated serum interleukin-6 levels. The high iodine content in the thyroid results in a poor response to thionamides, but patients benefit from perchlorate (1 g/d for no more than 40 days because of possible serious dose-dependent side effects). Hyperthyroidism can be exacerbated when perchlorate therapy is discontinued.

In type II, thyrotoxicosis results from presynthesized hormone release caused by amiodarone-induced thyroiditis [4] and therefore has acute onset in the absence of premonitory hormonal changes. Patients with this condition have normal results on thyroid examination, decreased radioactive iodine uptake, and markedly elevated serum interleukin-6 levels. Given the pathogenesis, no benefit from thionamide or perchlorate treatment is seen, but a prompt response to glucocorticoids occurs (prednisone, 40 mg/d or equivalent, slowly tapered over 2 to 3 months), mainly because of the membrane-stabilizing actions of these agents. If thyrotoxicosis is exacerbated during tapering, the glucocorticoid dose should temporarily be increased. Patients may subsequently develop self-limited spontaneous or iodine-induced hypothyroidism, and occasional cases of persistent subclinical hypothyroidism have been described [5].

There are probably mixed forms of amiodarone-induced thyrotoxicosis, both from the beginning and during follow-up. Other pathogenic mechanisms may play a role in certain cases. Recognition of the precise mechanism acting in a given patient will aid in management because thyrotoxicosis due to the type I mechanism will respond to thionamide plus perchlorate treatment and because thyrotoxicosis due to the type II mechanism will respond to glucocorticoids. Mixed forms should be managed with a combination of thionamide, perchlorate, and glucocorticoids. The general practice is to withdraw amiodarone if possible, although worsening of thyrotoxicosis with this practice has been described (probably because of loss of amiodarone antiadrenergic and 5' deiodinase inhibitory actions) and amiodarone-induced thyrotoxicosis has occasionally been controlled with conventional treatment despite amiodarone maintenance.