Normalization of peripheral thyroid hormone metabolism induced by successful chronic amiodarone treatment in patients with ventricular arrhythmias

Abstract

Amiodarone, an antiarrhythmic agent, is also known to have important effects on the peripheral metabolism of thyroid hormones; the relationship between these two effects of the drug, however, is not well established. We tested the hypothesis that the antiarrhythmic effect of amiodarone might be mediated by its effect on the metabolism of thyroid hormones. Peripheral thyroid hormone metabolism was investigated using a double-tracer ([125I]-T4 and [131I]-T3) procedure in 10 normal volunteers and 10 euthyroid patients with complex ventricular arrhythmias before and during 6 months' amiodarone treatment. The underlying cardiac disease was coronary artery disease in four cases, dilated cardiomyopathy in three and idiopathic arrhythmias in three. In all but one patient with complex ventricular arrhythmias amiodarone treatment resulted in a reduction of > or = 80% of premature ventricular contractions and complete suppression of episodes of ventricular pairs or ventricular tachycardia. In all cases successful treatment with amiodarone was accompanied by normalization of all kinetic parameters: T4 to T3 conversion ratio and T3/T4 molar ratio of production decreased to mean values of 24.7 +/- 17.5% and 0.35 +/- 0.22% respectively, whereas T4 production rate increased (mean value 75.9 +/- 30.0 nmol day-1 m-2). Our kinetic data indicate that long-term therapy with amiodarone, when effective in suppressing cardiac arrhythmias, also reduces peripheral T4 to T3 conversion, hence restoring the normal peripheral thyroid hormone metabolic pattern. In conclusion, our study confirms that the antiarrhythmic action of amiodarone may be (at least partially) mediated by its action on thyroid hormone metabolism, and may justify the hypothesis that an altered peripheral metabolism of thyroid hormones may play a role in the pathogenesis of complex ventricular arrhythmias.

Acute effects of intravenous amiodarone on sulphate metabolites of thyroid hormones in arrhythmic patients

“…Serum free T4 showed a tendency to increase (16·0 Ϯ 2·79 vs 14·9 Ϯ 3·62 pmol/l, on average an increase of 6·9%); this increase did not reach a statistical significance (at variance with the results reported in another of our papers, Iervasi et al, 1997) owing to the relatively high error in the free T4 assay (about 13%) (Iervasi et al, 1996). Serum free T4 showed a tendency to increase (16·0 Ϯ 2·79 vs 14·9 Ϯ 3·62 pmol/l, on average an increase of 6·9%); this increase did not reach a statistical significance (at variance with the results reported in another of our papers, Iervasi et al, 1997) owing to the relatively high error in the free T4 assay (about 13%) (Iervasi et al, 1996).…”

“…The sensitivity and between-assay precision of these methods have previously been reported (Iervasi et al, 1996). Serum total T4 and total T3 concentrations were measured by the fully automated immunoenzymometric assay AIA 600 system (TOSOH Corporation, Tokyo, Japan).…”

Low-T3 Syndrome

“…The interassay coefficient for all determinations ranged between 8% for TSH and 9.7% for TT4. 21 On the basis of fT3 values, patients were divided into two subgroups: group I, patients with low T3, ie, with fT3 below the lower limit of the reference interval (fT3 Ͻ3.1 pmol/L), and group II, patients with normal fT3 (Ն3.1 pmol/L).…”

Amiodarone Inhibits the 3,5,3′-Triiodothyronine-Dependent Increase of Sodium/Potassium Adenosine Triphosphatase Activity and Concentration in Human Atrial Myocardial Tissue

“…At the same time, because of its structural similarities to thyroid hormones, the drug is believed to cause in the heart several features that are characteristic of hypothyroidism (7,8). Amiodarone, or its active metabolite desethylamiodarone likely inhibits peripheral conversion of thyroxine (T 4 ) to T 3 and antagonizes the binding of T 3 to its nuclear receptors (9)(10)(11)(12). However, it is unclear whether, at least in part, amiodarone exerts its pharmacological effects by interfering with the action of thyroid hormone; the data regarding this issue are controversial (13,14).…”