Prevalence of Amiodarone-Induced Thyrotoxicosis and Associated Risk Factors in Japanese Patients

Abstract

Amiodarone is a widely used agent for life-threatening arrhythmias. Although amiodarone-induced thyrotoxicosis (AIT) is a major adverse effect that can cause recurrence of arrhythmias and exacerbation of heart failure, risk factors for AIT among amiodarone-treated Japanese patients have not been elucidated. Here, we investigated the prevalence and predictive factors for AIT. The study subjects were 225 patients treated with amiodarone between 2008 and 2012, who were euthyroid before amiodarone therapy. All patients with AIT were diagnosed by measurement of thyroid hormones and ultrasonography. Among the 225 subjects, 13 patients (5.8%) developed AIT and all the patients were classified as Type 2 AIT. Baseline features of patients with AIT were not different from those who did not develop AIT, except for age (AIT, 55.1 ± 13.8, non-AIT, 68.1 ± 12.0 years, P < 0.001). Multivariate analyses using the Cox proportional hazard model identified age as the sole determinant of AIT (hazard ratio: 0.927, 95% confidence interval: 0.891–0.964). Receiver operating characteristic curve analysis identified age of 63.5 years as the cutoff value for AIT with sensitivity of 70.3% and specificity of 69.2%. In summary, this study showed that the prevalence of AIT is 5.8% in Japanese patients treated with amiodarone and that young age is a risk factor for AIT.

Risk factors for amiodarone‐induced thyroid dysfunction in Japan

“…Consequently, a younger age at the initiation of amiodarone, DCM, and cardiac sarcoidosis were identified as independent risk factors for the development of amiodarone‐induced hyperthyroidism. Previous studies suggested that young age is a risk factor for amiodarone‐induced hyperthyroidism [12,13,19,35], and our results are consistent with these studies. Although, we cannot conclude that age at the initiation of amiodarone therapy was a clinically significant risk factor for amiodarone‐induced hyperthyroidism in the present study, given both the low sample size and the small effect size of the odds ratio.…”

“…The prevalence of amiodarone‐induced hyperthyroidism was higher in our study than in previous studies conducted in Asian countries [13,19,35] that included only patients with euthyroidism. The prevalence of amiodarone‐induced hyperthyroidism was previously reported to be 4.0% in Taiwan [19] and 6% in the Chinese population living in Hong Kong [13].…”

“…The prevalence of amiodarone‐induced hyperthyroidism was previously reported to be 4.0% in Taiwan [19] and 6% in the Chinese population living in Hong Kong [13]. Additionally, a recent study found that the prevalence of amiodarone‐induced hyperthyroidism was 5.8% in Japan [35]. In our study, patients with subclinical hyperthyroidism and hypothyroidism were included in the analysis in order to determine the predictors of amiodarone‐induced hypothyroidism and amiodarone‐induced hyperthyroidism in clinical practice.…”

“…Meanwhile, subclinical thyroid dysfunction, defined as altered TSH and normal thyroxine (T4) levels, has been reported in more than 10% of patients with heart failure or dilated cardiomyopathy (DCM) [32–34]. This suggests that subclinical thyroid dysfunction is not so rare in patients with cardiovascular diseases treated with amiodarone, whereas previous reports regarding the prevalence of risk factors for amiodarone‐induced thyroid dysfunction have focused only on patients with euthyroidism before amiodarone therapy [11,35]. Consequently, the impact of subclinical thyroid dysfunction on the development of amiodarone‐induced hyperthyroidism and amiodarone‐induced hypothyroidism is unclear.…”

Mixed Amiodarone-Induced Thyrotoxicosis Refractory to Medical Therapy and Plasmapheresis

“…Amiodarone-induced thyrotoxicosis (AIT) has been associated with increased mortality in older individuals with impaired ventricular function [1], underlying the importance of rapid restoration and maintenance of euthyroidism in this condition. Amiodarone has been reported to cause thyroid dysfunction in 15-20% of cases [1][2][3], with the incidence of thyrotoxicosis being approximately 5% [3,4]. Plasmapheresis as a treatment option for thyrotoxicosis refractory to medical therapy has shown mixed results.…”