Amiodarone-induced thyrotoxicosis: something new to refine the initial diagnosis?

Abstract

Amiodarone-induced thyrotoxicosis (AIT) is a clinical condition fraught with difficulties and uncertainties both from the diagnostic and therapeutic standpoints (1). Diagnosis and treatment are closely linked, because the diagnostic problems may affect the therapeutic approach and lead to suboptimal treatment and delayed resolution of dysfunction. This, in turn, is risky for the AIT patient, who generally has underlying heart abnormalities (arrhythmias, heart failure) for which prompt restoration and stable maintenance of euthyroidism represent fundamental actions (1). Indeed, AIT is associated with increased mortality, particularly in elderly patients with markedly impaired left ventricular function (2). Thus, at variance with amiodarone-induced hypothyroidism (3), AIT poses relevant and urgent therapeutic problems. What is difficult in AIT is not to diagnose the thyrotoxic state, but the pathophysiologic mechanism(s) underpinning it. Traditionally, although schematically, two main forms of AIT are distinguished (4). Type 1 AIT is a classical form of iodine-induced thyrotoxicosis associated with true hyperthyroidism; thyroid hyperfunction is triggered by the iodine load, and the thyroid gland generally is intrinsically abnormal owing to latent autonomy due to thyroid nodular or autoimmune disease. Type 2 AIT is a form of destructive thyroiditis caused by iodine or, more likely, amiodarone or its metabolite, desethylamiodarone; most cases develop in normal thyroid glands, although a small, diffuse or nodular goiter may sometimes be present. AIT may occur at any time during amiodarone therapy and even long after amiodarone withdrawal (1). Clinical presentation of the two forms does not differ (1). A relevant proportion (about 20%) of patients with type 2 AIT develop hypothyroidism in the long run (5). Type 1 AIT is treated with thionamides with or without potassium perchlorate, but it often is resistant to therapy because of the large intrathyroidal iodine stores (1); on the contrary, type 2 AIT is managed with oral glucocorticoids (6), but the time required to normalize thyroid status may vary depending mainly on thyroid volume and severity of baseline thyrotoxicosis (7).