Amiodarone and the Thyroid

Abstract

Amiodarone, an iodinated benzofuran derivative, was introduced in the 1960s as an antianginal agent with coronary vasodilator properties. Later description of its antiaiThythmic activity in animals and reports of its unique electrophysiological effects have led to its widespread application as an anti-arrhythmic agent Singh and Vaughan Williams first described the similarity between the effects of amiodarone and those of thyroidectomy on the duration of the atrial monophasic action potential [1]. A number of other features of the drug's action on the heart resemble those of hypothyroidism, for example development of bradycardia and reduction of myocardial oxygen consumption, changes which are reversed by simultaneous administration of thyroid hormones. There is, in addition, a structural similarity between thyroid hormones and amiodarone, each molecule of the drug containing two atoms of iodine. These properties of amiodarone have prompted examination of the relationship between the effects of the drug and those of thyroid hormones. A number of studies have reported the influence of amiodarone treatment in man on circulating concentrations of thyroid hormones [2,3]. Most studies describe increases in serum thyroxine (T4) and reverse triiodothyTonine (rT3) accompanied by a decrease in serum T3. These changes in thyroid hormone concentrations are evident a week after beginning drug treatment [3]. In our own study of long-term amiodarone treatment (treatment of greater than six months duration) [4] significant increases in serum total T4 and rT3 concentrations were found in patients receiving the drug in accord with previous reports. In parallel with a rise in total T4, an increase in free T4 concentration was evident in the treated group; one-third of subjects had a free T4 concentration above the normal range. Conversely, one-third of treated patients were found to have a serum free T3 concentration below the normal range. The influence of amiodarone treatment on levels of thyroid hormone binding proteins in serum was also studied; no effect of the drug on the major thyroid hormone binding protein, thyroxine binding globulin was found, but serum concentrations of thyroxine binding prealbumin and albumin were both reduced. These changes in both thyroid hormones and binding proteins were not confined to 'sick' patients with arrhythmias related to ischaemic heart disease and left ventricular dysfunction in whom non-specific effects of illness might be expected, but were also evident in 'healthy' subjects with supraventricular tachyarrhythmias secondary to accessory conducting pathways. In addition to the thyroid hormone effects described, we reported a small but significant increase in serum thyrotrophin (TSH) levels in amiodarone-treated patients; all TSH values remained within the normal range. Other groups have reported only a transient effect, serum TSH concentration returning to control levels 12 weeks after beginning treatment [3]. Variable effects of amiodarone on the TSH response to thyrotrophin releasing hormone