Adverse cardiovascular events in AIT

TOPIC: Amiodarone-induced thyrotoxicosis

Title: Amiodarone-induced thyrotoxicosis is a predictor of adverse cardiovascular outcome .

Authors: Yiu K-H, Jim M-H, Lee C-H, Yuen M, Mok M, Shea Y-F, Fan K, Tse H-F, & Chow W-H.

Reference: Journal of Clinical Endocrinology and Metabolism 94: 109-114, 2009



Whether the risk of long-term major adverse cardiovascular events (MACE) is higher in patients with amiodarone-induced thyrotoxicosis (AIT) than in euthyroid patients under chronic amiodarone treatment (EuAmio) is not clear.


To investigate the rate of MACE in AIT and EuAmio patients.

Patients & Methods

Retrospective study of 354 patients investigated in a tertiary referral center (Hong Kong) under amiodarone treatment for at least 3 months. Definition of MACE included cardiovascular mortality, myocardial infarction, stroke and heart failure, ventricular arrhythmias requiring hospitalization. Mean follow-up was 4 years.


AIT was found in 57 patients (16.1%), euthyroidism in 224 (63.3%), and hypothyroidism in 73 (20.6%). AIT patients had a higher MACE rate than EuAmio patients (31.6% versus 10.7%; P <0.01) mostly due to the higher rate of ventricular arrhythmias (7.0% versus 1.3%; P = 0.03). AIT and a left ventricular ejection fraction below 45% represented independent predictors of MACE.


In patients under chronic amiodarone treatment, the development of AIT is a major risk factor for the subsequent occurrence of MACE.


Amiodarone can cause either thyrotoxicosis or hypothyroidism in about 15-20% of patients treated long-term with this drug. The relative proportion of AIT or amiodarone-induced hypothyroidism is related to iodine intake, because AIT is relatively more frequent in iodine-deficient areas and amiodarone-induced hypothyroidism in iodine-sufficient areas. Because it occurs in patients with underlying cardiac problems, amiodarone-induced thyroid dysfunction, particularly AIT, represents a dangerous clinical condition which may aggravate pre-existing heart diseases and, therefore, warrants prompt correction and restoration of a euthyroid state. Despite these considerations, data on the long-term cardiovascular outcome in AIT patients, and, in particular, on the comparison of outcomes between AIT and EuAmio patients, are limited.

In this retrospective study, Yiu et al . evaluated a large series of amiodarone-treated patients and found an almost equal prevalence of thyrotoxic and hypothyroid patients, accounting for more than one third of the entire cohort of 354 patients. Although AIT and EuAmio groups did not differ at baseline as to clinical characteristics, AIT patients showed a much higher rate of MACE than EuAmio patients during the subsequent long follow-up. This difference was mainly caused by the higher rate of ventricular arrhythmias requiring hospitalization in AIT. Cox-regression multivariate analysis indicated that AIT and a left ventricular ejection fraction less than 45% were independent predictors of MACE.

This study has some limitations inherent to its retrospective design. For example, little information is given on the type of AIT (type 1 versus type 2) and description of the therapeutic strategy for AIT is not clearly indicated. These are important drawbacks, because identification of the type of AIT is crucial for a correct therapeutic approach which can substantially shorten the period of thyrotoxicosis and thereby reduce the risk posed by AIT for the heart. Despite these limitations, the study has the merit to show what all experts in the field had always thought and stated. i.e., that AIT is detrimental to the heart (particularly because the latter is, under most circumstances, sick to start with) and must be promptly and aggressively treated. In the last 20 years or so (in our experience), the proportion of type 1 AIT, developing on an abnormal thyroid gland (nodular goiter, preclinical Graves’ disease) has been steadily decreasing. One possible explanation is that cardiologists nowadays evaluate more carefully the thyroid function of their patients before starting amiodarone treatment (unless this is required in the emergency room), and avoid using the drug when the thyroid shows underlying (mostly undiagnosed) abnormalities. The much more prevalent type 2 AIT, occurring in a normal thyroid gland, is however unpredictable and may occur at any stage of amiodarone treatment, even after its withdrawal. This observation underscores the need for a close interaction between cardiologists and endocrinologists, and for a periodical evaluation of thyroid function in patients receiving amiodarone therapy chronically.

Full paper obtainable at doi: 10.1210/jc.2008-1907

Summary and Commentary prepared by Luigi Bartalena (Related to Chapters 5 and 13 of TDM)

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