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Aims: Thyroid dysfunction is considered the most frequent complication to amiodarone treatment, but data on its occurrence outside clinical trials are sparse. The present study aimed to examine the incidence of thyroid dysfunction following initiation of amiodarone treatment in a nationwide cohort of patients with and without heart failure (HF)., Methods and Results: In Danish registries, we identified all patients with first-time amiodarone treatment during the period 2000-18, without prior thyroid disease or medication. The primary outcome was a composite of thyroid diagnoses and initiation of thyroid drugs. Outcomes were assessed at 1-year follow-up, and for patients free of events in the first year, in a landmark analysis for the subsequent 5 years. We included 43 724 patients with first-time amiodarone treatment, of whom 16 939 (38%) had HF. At 1-year follow-up, the cumulative incidence and adjusted hazard ratio (HR) of the primary outcome were 5.3% and 1.37 (95% confidence interval 1.25-1.50) in patients with a history of HF and 4.2% in those without HF (reference). In the 1-year landmark analysis, the subsequent 5-year cumulative incidences and adjusted HRs of the primary outcome were 5.3% (reference) in patients with 1-year accumulated dose <27.38 g [corresponding to average daily dose (ADD <75 mg)], 14.0% and HR 2.74 (2.46-3.05) for 27.38-45.63 g (ADD 75-125 mg), 20.0% and HR 4.16 (3.77-4.59) for 45.64-63.88 g (ADD 126-175 mg), and 24.5% and HR 5.30 (4.82-5.90) for >63.88 g (ADD >175 mg)., Conclusion: Among patients who initiated amiodarone treatment, around 5% had thyroid dysfunction at 1-year follow-up, with a slightly higher incidence in those with HF. A dose-response relationship was observed between the 1-year accumulated amiodarone dose and the subsequent 5-year cumulative incidence of thyroid dysfunction., Competing Interests: Conflict of interest: J.H.B. received advisory board honoraria from Bayer, unrelated to the submitted work. E.F. received an independent research grant from Novo Nordisk Foundation, unrelated to the submitted work. L.K. received speaker’s honoraria from Novo, Novartis, AstraZeneca, and Boehringer, unrelated to the submitted work. S.L.K. received a speaker’s honoraria from Astra Zeneca outside of the submitted work. All remaining authors have declared no conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Amiodarone is a class III antiarrhythmic drug containing 37% iodine by weight, with a structure similar to that of thyroid hormones. Deiodination of amiodarone releases large amounts of iodine that can impair thyroid function, causing either hypothyroidism or thyrotoxicosis in susceptible individuals reflecting ~20% of patients administered the drug. Not only the excess iodine, but also the amiodarone (or its metabolite, desethylamiodarone) itself may cause thyroid dysfunction by direct cytotoxicity on thyroid cells. We present an overview of the epidemiology and pathophysiology of amiodarone-induced thyroid disorders, with a focus on the various forms of clinical presentation and recommendations for personalized management of each form., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose of Review: Amiodarone-induced thyroid dysfunction is well established and commonly encountered but is associated with several diagnostic and management challenges. The present review discusses recent evidence published related to the effects of amiodarone on the thyroid gland and thyroid function., Recent Findings: Retrospective studies to evaluate amiodarone-induced thyroid dysfunction in children show the occurrence of potential clinically significant changes within 2 weeks of amiodarone initiation that may not be detected if standard adult guidelines for thyroid hormone monitoring are followed. A small study evaluating beta-glucuronidase activity in amiodarone-induced thyrotoxicosis (AIT) demonstrated higher levels in patients with AIT type 2 compared to type 1. New data have suggested the incidence of agranulocytosis may be higher in patients on thionamides with AIT compared to hyperthyroidism because of other causes. In a small study, investigators demonstrated the use of a combination of intravenous and oral steroids to treat refractory AIT which needs to be evaluated in further controlled trials. Finally, recent data demonstrated a possible mortality benefit of surgery over medical therapy for AIT in patients with moderate to severe reduction in left ventricular ejection fraction., Summary: Recent research regarding the prevalence, diagnosis, and management of amiodarone-induced thyroid dysfunction were reviewed.

Context: Amiodarone is used in patients with arrhythmias, but thyroid dysfunction [amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH)] is a common adverse effect. As the onset of AIT and AIH has not been studied in children, the timing of dysfunction and long-term monitoring are not known in this population., Objective: To describe the incidence and timing of amiodarone-induced thyroid dysfunction in children and adolescents, with a secondary aim to identify risk factors for amiodarone-induced thyroid dysfunction, and to identify variance in thyroid hormone surveillance and treatment., Design: Retrospective review of thyroid dysfunction in children and young adults treated with amiodarone between 2007 and 2018., Setting: Children's Hospital of Philadelphia., Patients: Children and young adults treated with amiodarone., Main Outcome Measures: Prevalence of amiodarone-induced thyroid dysfunction., Results: Of 484 patients, 190 had thyroid-function testing; 17.3% were found to have subclinical hypothyroidism, and 13.7% testing developed hypothyroidism. Hyperthyroidism occurred in 2.1%. In patients with subclinical hypothyroidism, 63% returned to normal thyroid function without thyroid hormone replacement. Only 26% of patients with hypothyroidism had spontaneous normalization of thyroid function. Twenty-five percent of AIT patients had spontaneous normalization of thyroid function., Conclusions: This study looks at a pediatric and young-adult population in an effort to describe the natural history of amiodarone-induced thyroid dysfunction. Based on our data, we recommend that a complete thyroid-function panel be obtained within the first week and then at weekly intervals for the first 5 weeks after initiation. The majority of thyroid dysfunction was noted within the first 35 days of treatment., (Copyright © 2019 Endocrine Society.)

Although amiodarone is considered the most effective antiarrhythmic agent, its use is limited by a wide variety of potential toxicities. The purpose of this review is to provide a comprehensive "bench to bedside" overview of the ways amiodarone influences thyroid function. We performed a systematic search of MEDLINE to identify peer-reviewed clinical trials, randomized controlled trials, meta-analyses, and other clinically relevant studies. The search was limited to English-language reports published between 1950 and 2017. Amiodarone was searched using the terms adverse effects, hypothyroidism, myxedema, hyperthyroidism, thyroid storm, atrial fibrillation, ventricular arrhythmia, and electrical storm. Google and Google scholar as well as bibliographies of identified articles were reviewed for additional references. We included 163 germane references in this review. Because amiodarone is one of the most frequently prescribed antiarrhythmic drugs in the United States, the mechanistic, diagnostic and therapeutic information provided is relevant for practicing clinicians in a wide range of medical specialties., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Amiodarone is one of the most commonly prescribed antiarrhythmic agents in clinical practice owing to its efficacy, even with high toxicity profile. The high iodine content and the prolonged biological half-life of the drug can result in thyroid dysfunction in a high proportion of patients treated with amiodarone even after cessation of amiodarone. Both hypothyroidism and hyperthyroidism are common side effects that mandate regular monitoring of patients with thyroid function tests. Amiodarone-induced hypothyroidism (AIH) is diagnosed and managed in the same way as a usual case of hypothyroidism. However, differential diagnosis and clinical management of amiodarone-induced thyrotoxicosis (AIT) subtypes can be challenging. With the aid of a case snippet, we update the current evidence for the diagnostic work up and management of patients with amiodarone-induced thyroid dysfunction in this article., Competing Interests: There is no competing interests to declare among authors of this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Amiodarone is associated with significant long-lasting adverse drug reactions (ADRs). Guidelines recommend laboratory monitoring during long-term use. However, data of compliance with laboratory monitoring are lacking., Aims: The aim of this study was to assess laboratory monitoring of liver and thyroid function during amiodarone prescribing from 1989 to 2011 in the Tayside, UK, population (approximately 400 000) in relation to National Guidelines recommending laboratory monitoring every 6 months. We also report the population-level incidence of abnormal liver and thyroid function in relation to total exposure of amiodarone., Methods: Utilizing well-established record-linkage database, a longitudinal retrospective analysis of 1413 patients on long-term amiodarone was carried out, analyzing prescribing, biochemical, and clinical data., Results: Forty-six percent (46%), 28%, and 21% of patients underwent liver, thyroid, and combined testing, respectively, in accordance with guideline recommendations. Thirteen percent and 17% of patients did not have any ALT or TSH testing, respectively. During follow-up, 117 (9.5%) patients had an ALT 3×ULN and 16% patients had an abnormal TSH, (n=125, <0.4 mU/L and n=28, >10 mU/L). One hundred and forty patients (10%) required thyroxine replacement therapy, and 40 (3%) required on hyperthyroid medication. Total amiodarone exposure increased the likelihood of abnormal biochemical testing 2.5-fold after 4 years therapy for liver and thyroid function (P<.0005)., Conclusion: In this population-based study, adherence to laboratory monitoring guidelines was suboptimal. There was a positive correlation with total amiodarone exposure and biochemical abnormalities and development of thyroid disease compared to the general population, highlighting the need for improvement and continued amiodarone monitoring., (© 2017 John Wiley & Sons Ltd.)

Rationale, Aims and Objectives: Baseline thyroid function testing and regular follow-up of thyroid function under amiodarone usage was recommended by guidelines. Little is known about the status of amiodarone monitoring in real-world clinical care in Taiwan. The objective was to determine the rate of thyroid monitoring and to assess the clinical and physicians' characteristics associated with adequate monitoring in a tertiary referral centre for arrhythmia., Methods: We reviewed the medical records of patients receiving amiodarone during the period 2008-2009 at Taipei Veterans General Hospital. The rate of baseline and follow-up thyroid function monitoring during amiodarone therapy were calculated. Factors associated with guideline adherence to monitoring were analysed., Results: Among the 1319 enrolled cases, 36.4% (n = 480) underwent baseline thyroid function testing and 1.1% (n = 15) received measurement of anti-thyroid peroxidase antibody before amiodarone initiation. Regular follow up of thyroid function under amiodarone usage occurred in only 8.6% (n = 114) of cases. Baseline thyroid function was more likely to be present in patients of younger age (P < 0.001), female sex (P = 0.01), and in those who received amiodarone therapy from cardiologists (P < 0.001) or electrophysiologists (P < 0.001) with fewer years of service (P < 0.001). Upon multivariate analysis, only physicians' expertise (cardiologist versus non-cardiologist, OR = 5.67, 95% CI: 2.44-13.16) and years of service (OR = 0.97, 95% CI: 0.95-0.998) were significantly associated with adequate thyroid monitoring., Conclusions: The rate of thyroid monitoring with amiodarone therapy had been suboptimal. Strategies to enhance guideline adherence are needed., (© 2016 John Wiley & Sons, Ltd.)

Background: Amiodarone is known to affect the thyroid, but little is known about thyroid recovery after short-term amiodarone treatment., Objectives: We aimed to evaluate the impact of 8weeks of amiodarone treatment on thyroid function in patients with atrial fibrillation (AF) undergoing catheter ablation in a randomised, double-blind clinical trial., Methods: 212 patients referred for AF ablation at two centres were randomized to 8weeks of oral amiodarone or placebo. Thyroid function tests (TSH, thyroid stimulating hormone; T4, thyroxine; T3, triiodothyronine; fT4, free T4; fT3, free T3) were performed at baseline and 1, 3 and 6months., Results: Study drug was discontinued due to mild thyroid dysfunction in 1 patient in the placebo vs. 3 in the amiodarone group (p=0.6). In linear mixed models there were significant effects of amiodarone on thyroid function tests, modified by follow-up visit (p<10(-9) for both TSH, T4, T3, fT4 and fT3). The amiodarone group had higher TSH, fT4 and T4 after 1 and 3months compared to placebo, whereas T3 and fT3 were lower. In all cases, the amiodarone-induced thyroid dysfunction was largest at 1month, declining at 3months, and with no differences at 6months, compared to baseline., Conclusion: We found amiodarone to have a significant impact on thyroid function after only 1month, but with a fast recovery of thyroid function after amiodarone discontinuation. Our study indicates that short-term amiodarone can be considered safe in patients without prior thyroid dysfunction., (Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Amiodarone is an antiarrhythmic drug frequently used in everyday clinical practice. Its mechanism of action involves the interaction with many receptors, including those in the cardiac conduction system. Amiodarone usefulness is protect in the treatment of a variety of tachyarrhythmias, both benign and life-threatening. In contrast to other antiarrhythmic drugs, amiodarone is characterized by high therapeutic efficacy, both in patients with normal and impaired left ventricular systolic function. A significant limitation of its is associated with side effects including thyroid gland dysfunction. Disturbances of this organ associated with amiodarone are an important diagnostic and therapeutic problem. They may contribute to the occurrence of both Amiodarone- Induced Thyrotoxicosis (AIT) and Amiodarone-Induced Hypothyroidism (AIH). The risk of such complications should be considered for each patient individually, taking into account thyroid function at the beginning of pharmacotherapy. Appropriate procedure, both before and after treatment allows a rapid diagnosis and treatment of thyroid disturbances. It seems that the best parameter used to assess the hormonal imbalance during amiodarone therapy is the concentration of the free triiodothyronine (fT3). The evaluation of thyroid function should be performed before starting pharmacotherapy, and then repeated every six months. In the case of a thyroid dysfunction, assessment must be performed immediately according to standard diagnostic and therapeutic regimens. Despite abnormal thyroid function, high efficiency of amiodarone and relatively small risk of thyroid damage allows continuation therapy. Amiodarone therapy requires a care from both cardiologist and endocrinologist. The aim of this paper is to present the state of art of evaluation of the thyroid function and procedures implemented in care of thyroid dysfunction before and during treatment with amiodarone., (© 2016 MEDPRESS.)

Amiodarone is a benzofuran derivative that contains up to 40% of iodine. Amiodarone is used for treatment and prevention of life threatening supraventricular and ventricular tachyarrhythmias. The effects on thyroid gland vary from abnormalities in thyroid function tests to overt amiodarone induced hypothyroidism (AIH) and thyrotoxicosis (AIT). Patients with AIH are treated with L-thyroxine and may continue treatment with amiodarone. Two different forms of AIT have to be distinguished: amiodarone induced hyperthyroidism (AIT I) and thyroiditis (AIT II). AIT I is treated with antithyroid drugs, while total thyroidectomy and iodine-131 are used for definitive treatment. AIT II is treated with glucocorticoids. Patients with AIT have to stop treatment with amiodarone. Dronedarone is a less potent antiarrhythmic agent with structural and pharmacological properties similar to amiodarone. Dronedarone is devoid of iodine with fewer adverse effects and therefore it may be used in high risk patients for development of AIT or AIH.

Aim: the analysis of therapeutic approach in patients with basic heart condition and amiodarone induced thyroid dysfunction--correlations with the evolution and prognosis., Material and Methods: The study included 215 patients, 90 men and 125 women aged between 35 and 87, with different cardiac pathologies hospitalized in the Cardiology Clinic between 2004-2014, who received amiodarone treatment, in most cases for prophylaxis of various arrhythmias, both supraventricular and ventricular. During the evolution, these patients have developed amiodarone-induced thyroid dysfunction (hypo- or hyper function)., Results and Discussion: The evaluation of thyroid function after starting treatment was performed in 187 patients (86.97%). Diagnosis of amiodarone-induced thyroid dysfunction was based on hormonal dosages of TSH, FT4 and FT3, endocrinological examination and thyroid ultrasound. Thyroid dysfunction treatment was initiated, depending on the situation, in all patients during the hospitalization. Treatment included anti thyroid drugs or hormones substitution and in some cases a minimal dose of prednisone., Conclusions: Thyroid dysfunction regardless of the type (with hypo- or hyper function) requires continuous changes of the cardiovascular treatment, and association, where appropriate, with thyroid dysfunction medication. In some cases the latter determines cardiovascular side effects, for instance corticotheraphy may become a factor of imbalance for the hemodynamic status of the patient (by fluid retention, increased blood pressure, hyper glycemia).

Purpose: Determining the nature of the relationship between cumulative duration of exposure to an agent and the hazard of an adverse outcome is an important issue in environmental and occupational epidemiology, public health and clinical medicine. The Cox proportional hazards regression model can incorporate time-dependent covariates. An important class of continuous time-dependent covariates is that denoting cumulative duration of exposure., Methods: We used fractional polynomial methods to describe the association between cumulative duration of exposure and adverse outcomes. We applied these methods in a cohort study to examine the relationship between cumulative duration of use of the antiarrhythmic drug amiodarone and the risk of thyroid dysfunction. We also used these methods with a conditional logistic regression model in a nested case-control study to examine the relationship between cumulative duration of use of bisphosphonate medication and the risk of atypical femur fracture., Results: Using a cohort design and a Cox proportional hazards model, we found a non-linear relationship between cumulative duration of use of the antiarrhythmic drug amiodarone and the risk of thyroid dysfunction. The risk initially increased rapidly with increasing cumulative use. However, as cumulative duration of use increased, the rate of increase in risk attenuated and eventually levelled off. Using a nested case-control design and a conditional logistic regression model, we found evidence of a linear relationship between duration of use of bisphosphonate medication and risk of atypical femur fractures., Conclusions: Fractional polynomials allow one to model the relationship between cumulative duration of medication use and adverse outcomes., (© 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.)

Various drugs may cause thyroid dysfunction. The drugs which may cause thyrotoxicosis include interferon, molecular-targeted agents, amiodarone, thyroid hormone itself and so on. Those which cause hypothyroidism include anti-thyroid drugs, lithium and iodine etc. which inhibit thyroid hormone synthesis and secretion, and dopamine etc. which block TSH secretion. Those drugs which alter the thyroid hormone metabolism or the binding to TBG or those inhibit thyroid hormone absorption may cause hypothyroidism or deteriorate it in patients with hypothyroidism treated with thyroid hormone or those with diminished reserved capacity. When thyroid dysfunction occurred, it is better to discontinue the causative drug, but in many cases, the patients are forced to be treated with the drug being continued.

Amiodarone is an effective anti-arrhythmic agent for control of various life threatening ventricular tachyarrhythmias but may give Various side effects. Clinically relevant thyroid dysfunction is not uncommon during amiodarone therapy and is caused by iodide excess and inhibition of deiodinase activity. Amiodarone induced thyroid dysfunction varies from asymptomatic variation in thyroid function to clinically overt hypothyroidism and thyrotoxicosis. Prolonged elimination and half life and associated complications warrant for rational prescribing and long term follow up.

Amiodarone treatment is associated with the occurrence of thyroid dysfunction. The aim was to determine the incidence of amiodarone-induced thyroid dysfunctions and the influence of gender, age, treatment duration, goiter, thyroid antibodies, thyroid echogenicity and family history on their appearance. Of 248 consecutive patients, 144 males and 104 females, referred to thyroid status screening, 16% were with clinical dysfunction, 21% with sub-clinical dysfunction and 63% were euthyroid. The presence of goiter and thyroid peroxidase antibodies were the significant individual predictive factors for the occurrence of clinical dysfunction, and in the multivariate regression model, the presence of goiter was a significant predictive factor with the prognostic value of 80%. For sub-clinical dysfunction, the significant individual predictive factors were female gender and the presence of goiter, as well as in the multivariate regression model, with the prognostic value of 74.5% for female gender and 77.5 % for the presence of goiter. It is necessary to check the thyroid status both before and during amiodarone treatment. Administration of other anti-arrhythmic drugs and/or more frequent check-ups of the thyroid status should be taken into consideration in patients at higher risk, i.e. women with positive thyroid peroxidase antibodies and goiter.

Background: Amiodarone is associated with dysfunction of the thyroid. Concerns have arisen regarding the potential for adverse effects with generic formulations of amiodarone. We evaluated and compared the risk of thyroid dysfunction between patients using brand-name versus generic formulations of amiodarone and identified risk factors for thyroid dysfunction., Methods: We conducted a retrospective cohort study of patients with atrial fibrillation aged 66 years and older. We used administrative databases that linked information on demographics and clinical characteristics, claims for prescription drugs and discharges from hospital. We estimated thyroid dysfunction using person-year incidence., Results: Of the 60,220 patients in the cohort, 2804 (4.7%) used the brand-name formulation of amiodarone and 6278 (10.4%) used the generic formulation. Baseline characteristics between these two groups were comparable. The median maintenance dose of amiodarone was 200 mg/d for both groups. The total incidence rate for thyroid dysfunction was 14.1 per 100 person-years for both formulations. The mean time to clinical dysfunction of the thyroid was 4.32 years for the brand-name formulation and 4.09 years for the generic formulation. In a multivariate analysis, there was no significant difference in the incidence rates of thyroid dysfunction between the generic and brand formulations (hazard ratio 0.97, 95% confidence interval 0.87-1.08). Factors associated with an increased risk of thyroid dysfunction were being a woman, increasing age and having chronic obstructive pulmonary disease., Interpretation: In this population-based study, we saw no difference between brand-name and generic formulations of amiodarone in terms of incidence of thyroid dysfunction.

Objective: To determine the frequency, risk factors, clinical features, and management of amiodarone-induced thyroid dysfunctions., Design: Retrospective study., Setting: A regional hospital in Hong Kong., Patients: Patients who had been prescribed amiodarone for at least 6 months from 1 October 2005 to 30 September 2007., Results: A total of 390 patients (mean age, 70 years; standard deviation, 9 years; 54% male) with a median follow-up of 43 (interquartile range, 25-69) months were studied. Hypothyroidism developed in 87 (22%) of the patients (mean age, 72 years; standard deviation, 7 years; 56% male) and thyrotoxicosis in 24 (6%) of the patients (65 years; 11 years; 54% male). Increased baseline thyrotropin (thyroid-stimulating hormone) level appeared to be predictive of amiodarone-induced hypothyroidism, in which a thyroid-stimulating hormone level of 4 mIU/L or above was associated with a 4.7-fold increase in the risk (95% confidence interval, 1.9-11.7; P<0.001). Compared with those who remained euthyroid on amiodarone, thyrotoxicosis developed in younger patients. In these patients, the classical symptoms of thyroid dysfunction were frequently absent, although worsening of underlying arrhythmias, their cardiac condition, weight loss, and over-warfarinisation were suggestive of amiodarone-induced thyrotoxicosis. In both amiodarone-induced thyrotoxicosis and hypothyroidism, the disease course was benign. Patients with the former showed a good response to anti-thyroid drugs and steroid therapy., Conclusions: Amiodarone-induced thyroid dysfunction is common among our population. As the clinical presentations are usually vague and atypical, regular biochemical monitoring of thyroid function is warranted, particularly in patients with elevated baseline thyroid-stimulating hormone level. The disease course of amiodarone-induced thyrotoxicosis is usually benign and remits with timely administration of anti-thyroid medications, with or without corticosteroids.

Introduction: We compared the efficacy and safety of amiodarone and dronedarone in patients with persistent atrial fibrillation (AF)., Methods: Five hundred and four amiodarone-naïve patients were randomized to receive dronedarone 400 mg bid (n = 249) or amiodarone 600 mg qd for 28 days then 200 mg qd (n = 255) for at least 6 months. Primary composite endpoint was recurrence of AF (including unsuccessful electrical cardioversion, no spontaneous conversion and no electrical cardioversion) or premature study discontinuation. Main safety endpoint (MSE) was occurrence of thyroid-, hepatic-, pulmonary-, neurologic-, skin-, eye-, or gastrointestinal-specific events, or premature study drug discontinuation following an adverse event., Results: Median treatment duration was 7 months. The primary composite endpoint was 75.1 and 58.8% with dronedarone and amiodarone, respectively, at 12 months (hazard ratio [HR] 1.59; 95% confidence interval [CI] 1.28-1.98; P < 0.0001), mainly driven by AF recurrence with dronedarone compared with amiodarone (63.5 vs 42.0%). AF recurrence after successful cardioversion was 36.5 and 24.3% with dronedarone and amiodarone, respectively. Premature drug discontinuation tended to be less frequent with dronedarone (10.4 vs 13.3%). MSE was 39.3 and 44.5% with dronedarone and amiodarone, respectively, at 12 months (HR = 0.80; 95% CI 0.60-1.07; P = 0.129), and mainly driven by fewer thyroid, neurologic, skin, and ocular events in the dronedarone group., Conclusion: In this short-term study, dronedarone was less effective than amiodarone in decreasing AF recurrence, but had a better safety profile, specifically with regard to thyroid and neurologic events and a lack of interaction with oral anticoagulants.

Purpose of the Report: To compare thyroid imaging using Tc-99m sestamibi with the standard Tc-99m pertechnetate scintigraphy in patients on chronic use of amiodarone., Materials and Methods: A total of 23 patients on oral amiodarone for at least 4 months had thyroid scintigraphy and uptake measurement using Tc-99m pertechnetate and Tc-99m sestamibi. Thyroid function was evaluated by measuring serum concentrations of thyrotropin, free thyroxine, and free triiodothyronine, and antithyroglobulin and antithyroperoxidase antibodies., Results: Ten of the 23 patients were euthyroid, 9 hypothyroid, and 4 hyperthyroid, with normal, increased, and decreased serum thyrotropin, respectively. All euthyroid patients had markedly decreased thyroid Tc-99m pertechnetate uptake and normal or slightly increased Tc-99m sestamibi uptake, except for one patient who had increased uptake of both radiotracers. One of the 4 hyperthyroid patients had Graves' disease and markedly increased thyroid uptake of both tracers. The other 3 hyperthyroid patients had normal or decreased Tc-99m pertechnetate uptake and increased Tc-99m sestamibi uptake. Differently than expected, all 9 hypothyroid patients had normal or increased uptake of both radiopharmaceuticals., Conclusions: This study suggests that Tc-99m sestamibi may be an alternative tracer for thyroid scintigraphy and uptake measurement of patients on chronic use of amiodarone. Tc-99m sestamibi seems to be better than Tc-99m pertechnetate for the scintigraphic evaluation of the thyroid of euthyroid and hyperthyroid patients.

Amiodarone is a benzofuran derivative approved for the treatment of cardiac arrhythmias. Traditionally classified as a class III antiarrhythmic agent, amiodarone possesses electrophysiologic properties of all four Vaughan-Williams classes. This drug, however, has high iodine content, and this feature plus the intrinsic effects on the body make amiodarone especially toxic to the thyroid gland. Treatment can result in a range of effects from mild derangements in thyroid function to overt hypothyroidism or thyrotoxicosis. The diagnosis and treatment of amiodarone-induced hypothyroidism is usually straightforward, whereas that of amiodarone-induced thyrotoxicosis and the ability to distinguish between the type 1 and type 2 forms of the disease are much more challenging. Dronedarone was approved in 2009 for the treatment of patients with atrial fibrillation. As amiodarone, dronedarone is a benzofuran derivative with similar electrophysiologic properties. In contrast to amiodarone, however, dronedarone is structurally devoid of iodine and has a notably shorter half-life. In studies reported before FDA approval, dronedarone proved to be associated with significantly fewer adverse effects than amiodarone, making it a more attractive choice for patients with atrial fibrillation or flutter, who are at risk of developing amiodarone-induced thyroid dysfunction.

Background: Recently, the G allele of the cytotoxic T-lymphocyte-associated factor 4 (CTLA-4) exon 1 single-nucleotide polymorphism (CTLA-4 A/G(49)) has been identified as the most informative marker in patients with Graves' disease. Patients with the G/G genotype are refractory to medical treatment and frequently relapse after discontinuation of antithyroid drugs. Therefore, we analyzed CTLA-4 A/G(49) in patients who had been treated with (131)I. Further, a preliminary report has suggested that amiodarone-associated thyroid dysfunction (AATD) has a relationship with human leukocyte antigen (HLA) class I and class II., Method: CTLA-4 genotypes in exon 1 (A/G(49)) and CT60 were analyzed in 415 Japanese patients with Graves' disease and 65 patients with AATD., Results: The frequencies of the G alleles and G/G genotype at the both polymorphisms were significantly higher in Graves' patients compared with normal subjects. Compared with CT60, the frequencies of the G alleles and G/G genotypes at the A/G(49) were more significantly higher in patients with persistently positive thyrotropin receptor antibody despite >5 years of antithyroid drug therapy, compared with those whose thyrotropin receptor antibody became negative in <5 years (p < 0.0001). Consequently, the frequencies of the G/G genotype and G allele at the A/G(49) were also significantly higher in patients with Graves' disease who received (131)I therapy (p < 0.05). However, there was no significant difference in the A/G polymorphisms in the 65 patients with AATD., Conclusions: The G/G genotype in exon 1 (A/G(49)) is frequently expressed in Graves' disease patients who are refractory to antithyroid drug treatment. Therefore, the G/G genotype in A/G(49) would be a useful predictor of Graves' patients who are suitable for radioiodine therapy. Although the number of analyzed patients was small, our preliminary data suggest that the CTLA-4 gene polymorphisms might be unassociated with AATD.

Amiodarone and dronedarone are two clinically important benzofuran derivatives. Amiodarone has been used widely for treating resistant tachyarrhythmias in the past three decades. However amiodarone and its main metabolically active metabolite desethylamiodarone can adversely affect many organs, including the thyroid gland. Amiodarone-induced thyroid disorders are common and often present as a management challenge for endocrinologists. The pathogenesis of amiodarone-induced thyroid dysfunction is complex but the inherent effects of the drug itself as well as its high iodine content appear to play a central role. The non-iodinated dronedarone also exhibits anti-arrhythmic properties but appears to be less toxic to the thyroid. This review describes the biochemistry of benzofuran derivatives, including their pharmacology and the physiology necessary for understanding the cellular mechanisms involved in their actions. The known effects of these compounds on thyroid action are described. Recommendations for management of amiodarone-induced hypothyroidism and thyrotoxicosis are suggested. Dronedarone appears to be an alternative but less-effective anti-arrhythmic agent and it does not have adverse effects on thyroid function. It may have a future role as an alternative agent in patients being considered for amiodarone therapy especially those at high risk of developing thyroid dysfunction but not in severe heart failure.

Amiodarone is a frequently used antiarrhythmic drug with a high antiarrhythmic potency. However, beside its antiarrhythmic effects Amiodarone also reveals a variety of adverse effects and drug-related complications. The affected organs include the eyes, skin, lungs, nervous system, liver, gastrointestinal tract and the thyroid. The thyroid is one of the most frequently affected organs by Amiodarone. An altered hormone equilibrium always occurs and has to be distinguished from Amiodarone induced hyperthyroidism and hypothyroidism. The differentiation of these states frequently causes problems and may even be a diagnostic and therapeutic challenge in certain cases. The article gives an overview on the interactions between Amiodarone and the thyroid, the diagnostic and therapeutic options and management strategies of patient on Amiodarone therapy in the view of thyroid function.

Background: Many patients receiving amiodarone therapy are male. The long-term risk for amiodarone-induced thyroid dysfunction in these patients has not been systematically and prospectively investigated. The purpose of this study was to determine the extent of amiodarone-induced thyroid dysfunction in a large male cohort., Methods: This is a substudy of a prospective randomized controlled trial (SAFE-Trial) in which amiodarone, sotalol, and placebo for persistent atrial fibrillation were evaluated. For the purpose of this substudy, sotalol and placebo groups were combined into a control group. Serial thyroid function tests were performed over 1-4.5 years. Of the 665 patients enrolled in the SAFE-Trial, 612 patients were included in this sub-study., Results: Subclinical hypothyroidism, thyroid-stimulating hormone (TSH) level 4.5-10 mU/L, was seen among 25.8% of the amiodarone-treated patients and only 6.6% of controls (P <.0001). Overt hypothyroidism, TSH level >10 mU/L, was seen among 5.0% of the amiodarone-treated patients, and only 0.3% of controls (P <.001). By 6 months, 93.8% of the patients who developed TSH elevations above 10 mU/L on amiodarone had been detected. There was a trend toward a greater proportion of hyperthyroidism, defined as a TSH <0.35 mU/L, in the amiodarone group compared with the control group (5.3% vs 2.4%, P=.07)., Conclusions: Hypothyroidism developed in 30.8% of older males treated with amiodarone and in only 6.9% of the controls. Hypothyroidism presented at an early stage of therapy. Hyperthyroidism occurred in 5.3% of amiodarone treated patients, and was a subclinical entity in all but 1 case.

Amiodarone is commonly used to treat supraventricular and ventricular arrhythmias in various inpatient and outpatient settings. Over- and under-use of amiodarone is common, and data regarding patterns of use are sparse and largely anecdotal. Because of adverse drug reactions, proper use is essential to deriving optimal benefits from the drug with the least risk. This guide updates an earlier version published in 2000, reviews indications for use of amiodarone and recommends strategies to minimize adverse effects. The recommendations included herein are based on the best available data and the collective experience of the member of the writing committee.

Amiodarone is a potent class III anti-arrhythmic drug used in clinical practice for the prophylaxis and treatment of many cardiac rhythm disturbances, ranging from paroxismal atrial fibrillation to life threatening ventricular tachyarrhythmias. Amiodarone often causes changes in thyroid function tests mainly related to the inhibition of 5'-deiodinase activity resulting in a decrease in the generation of T3 from T4 with a consequent increase in rT3 production and a decrease in its clearance. In a group of amiodarone-treated patients there is overt thyroid dysfunction, either amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH). AIT is primarily related to excess iodine-induced thyroid hormone synthesis in an abnormal thyroid gland (type I AIT) or to amiodarone-related destructive thyroiditis (type II AIT). The pathogenesis of AIH is related to a failure to escape from the acute Wolff-Chaikoff effect due to defects in thyroid hormonogenesis, or, in patients with positive thyroid autoantibody test, to concomitant Hashimoto's thyroiditis. Both AIT and AIH may develop either in apparently normal thyroid glands or in glands with preexisting, clinically silent abnormalities. AIT is more common in iodine-deficient regions of the world, whereas AIH is usually seen in iodine-sufficient areas. In contrast to AIH, AIT is a difficult condition to diagnose and treat, and discontinuation of amiodarone is usually recommended. In this review we analyse, according to data from current literature, the alterations in thyroid laboratory tests seen in euthyroid patients under treatment with amiodarone and the epidemiology and treatment options available of amiodarone-induced thyroid dysfunctions (AIT and AIH).

The use of several groups of medications may result in thyroid dysfunction including thyrotoxicosis or hypothyroidism of various degree (from subclinical to full-clinical syndrome). The mentioned disturbances may develop either on the basis of normal euthyroid gland or may overlap the previously-existing oceult changes (first of all different forms of autoimmune thyroiditis). Amiodarone is a widely used anti-arrythmic drug with considerable potential to cause thyroid dysfunction because of its 35% iodine content. Besides amiodarone particles are known to inhibit T4 to T3 conversion, they work as inhibitors of nuclear receptors for thyroid hormones, exert cytotoxic effect and induce immune/inflammatory process in thyroid gland. Both thyrotoxicosis (AIT - amiodarone induced thyrotoxicosis) and hypothyroidism (AIH - amiodarone induce hypothyroidism) may develop during amiodarone therapy. AIT appears to occur more frequently in geographical areas with low iodine intake, whereas AIH is more frequent in iodine-sufficient areas. Two forms of AIT are known. Their differentiation is very important for further therapeutical procedures. Because thyrotoxicosis and hypothyroidism symptoms during amiodarone therapy are scanty, there is need for periodic determination of thyroid function. Normal ranges for amiodarone patients differ from those for the rest of population. They are presented in this review. Treatment of AIT is very complicated. Sometimes there is need to use few methods together, especially when amiodarone treatment can not be stopped.

The authors of the study investigated the effects of pharmacological doses of iodine as an ingredient of amiodaron, an anti-arrhythmic agent, and iodine radiopaque contrast agents (RCA), on the thyroid gland (TG) function. The subjects were 133 patients aged 60.5 +/- 8.5 years, who had been taking amiodaron for 12 to 164 months, and 164 patients aged 59.4 +/- 9.1 years, who were examined before coronarography (CAG) with RCA, and 1, 3, 6, and 12 months after the procedure. Serum levels of TSH, FT4, FT3, TG antibodies, TPO antibodies, and urine iodine level were measured; TG ultrasonography was performed. Forty-nine (51.9%) out of the 133 patients on amiodaron therapy developed thyroid disfunction. Subclinical hypothyroidism (24 cases; 18%) and manifest thyrotoxicosis (21 case; 15.8%) prevailed among functional TG disorders. Thirty-one per cent of the patients with thyrotoxicosis had preceding TG diseases; 70% of the thyrotoxicosis patients had a cardiac arrhythmia relapse. The concentration of thyroid antibodies did not change in patients with normal TG. The patients who underwent CAG displayed elevated renal iodine excretion 1, 3, and 6 months after RCA administration. Thyroid disfunction (thyrotoxicosis in 7.6% of the cases; hypothyroidism in 15.8% of cases) was revealed in 23.4% of the patients with preceding TG diseases one month after CAG. Cardial pathology exacerbation was observed in patients with thyrotoxicosis.

Objective: To determine the prevalence of thyroid dysfunction in patients receiving amiodarone, and the possible associated factors. The study also aimed at assessing the effect of amiodarone on thyroid function through the application of a questionnaire to cardiologists., Method: Fifty-six patients chronically (> 3 months) receiving amiodarone were assessed by measurement of their serum levels of TSH, free T4, total T3, and anti-TPO antibodies. Patients with changes in TSH levels were defined as having thyroid dysfunction (TD)., Results: The prevalence of thyroid dysfunction was 33.9%. No difference was observed between this group and that of patients with no dysfunction, except for the greater prevalence of anti-TPO positivity in patients with TD (P=0.02). Subclinical hypothyroidism was diagnosed in 10 (17.9%) patients and clinical hypothyroidism in 6 (10.7%). The prevalence of subclinical hyperthyroidism was 3.6% and that of clinical hyperthyroidism was 1.8%. Anti-TPO antibodies were positive in 5 (8%) patients (of whom, 4 had thyroid dysfunction). When compared with patients negative for anti-TPO antibodies, that group had a greater prevalence of dysfunction (80% vs 29.4%; P=0.04). Only 49.2% of the cardiologists routinely treated their patients' thyroid function, and the prevalence of the referred dysfunction for most of them ranged from 1 to 10%., Conclusion: The prevalence of thyroid dysfunction in our population was high, showing the need for implementing a laboratory routine. The cardiologists disagreed greatly in regard to the type of follow-up required for patients using amiodarone.

Amiodarone is a benzofuranic-derivate iodine-rich drug widely used for the treatment of tachyarrhythmias. In 14-18% of amiodarone-treated patients, there is overt thyroid disfunction, either amiodarone-induced hyperthyroidism (AIT) or amiodarone-induced hypothyroidism (AIH). Both AIT and AIH, may develop in apparently normal thyroid glands or in glands with preexisting, clinically silent abnormalities. In this article the author review the problems concerning the diagnosis and treatment of these two different situations.

During 1 year of amiodarone intake development of amiodarone-associated thyroid dysfunction was observed in 25% of patients (hypothyroidism and thyrotoxicosis in 19.2 and 5.8%, respectively). Development of hypothyroidism was not accompanied with loss of antiarrhythmic efficacy of amiodarone and therapy with L-thyroxin was conducted at the background of continued amiodarone intake. In all patients with clinical and in less than one half (47.6%) of patients with subclinical forms of hypothyroidism replacement therapy with L-thyroxin was carried out. Development of amiodarone-associated thyrotoxicosis was accompanied with loss of antiarrhythmic efficacy of amiodarone in all cases. In all patients with thyrotoxicosis which developed during amiodarone intake thyrostatic therapy with mercasolil was carried out and in case of its inefficacy prednisolone was added. In 87.5% of patients with thyrotoxicosis correction of the thyroid status was conducted under conditions of continued amiodarone intake as this drug had been prescribed because of life saving indications. Achievement of euthyroid state was followed by restoration of antiarrhythmic efficacy of amiodarone. Amiodarone was discontinued just in 1 patient with ventricular extrasystole as correction of thyroid status and restoration of euthyroidosis enabled effective use of other antiarrhythmic drugs.

Amiodarone is an antiarhytmic drug used in many clinical situations for its probed effect; it is also preferred in particular groups of patients (heart failure, post-ischemical) for its safe and its prognostic benefits. However, a substantial proportion of amiodarone treated patients develop either hypothyroidism or thyrotoxicosis. Both abnormalities may occur in apparently normal glands or in glandes with pre-existed abnormalities. It may be difficult to recognize the dysfunction because of the many changes in thyroid function test results that occur in euthyroid patients who are receiving amiodarone. Hypothyroidism is a well defined clinical situation managable thanks to common guidelines. The occurrence of hypothyroidism does not necessitate withdrawing amiodarone while instituting L-T4 replacement therapy, although many cases are transient and will spontaneously remit after amiodarone withdrawal. At the opposite, hyperthyroidism needs more attention to be diagnosed and to be treated, in fact there is a "personal" clinical-therapeutical behave towards it, caused by the lack of big trials made on this clinical situation. Effective strategies exist for the management of thyroid dysfunction, these should be tailored to the needs of the individual patient.

Background: In recent years we have observed new cases of thyroid disease occurring after heart transplantation (HTx). In these patients, the presence of this disease complicates their post-transplant course and occasionally results in life-threatening thyrotoxicosis. The present study examines the incidence and risk factors of thyroid disease in these patients with special emphasis on the use of amiodarone before HTx. Recommendations for follow-up of thyroid disease in HTx patients are discussed., Methods: A study was performed on a cohort of 380 patients who received HTx in Rotterdam between January 1, 1985 and April 1, 2001. Twenty patients (5%) developed thyroid dysfunction after HTx, 10 of whom had been treated with amiodarone before HTx., Results: Cumulative survival curves showed that most patients (60%) developed thyroid dysfunction within the first year after HTx (median interval between HTx and diagnosis was 9 months). Using univariate Cox regression analysis, amiodarone was a significant predictor for the development of thyroid dysfunction (hazards ratio 5.2, 95% confidence interval 2.5 to 10.8). After adjustment for age, gender, heart disease and Quetelet index, amiodarone remained a significant predictor., Conclusions: Our study clearly shows that, despite discontinuation of amiodarone treatment at the time of the HTx procedure, patients remain at risk for developing thyroid disease. HTx recipients treated with amiodarone before HTx should therefore be monitored carefully for development of thyroid dysfunction, especially within the first post-transplant year.

Amiodarone is licensed for the treatment of severe cardiac rhythm disorders where other treatments either cannot be used or have failed. Because of safety concerns, the summary of product characteristics (SPC) recommends that amiodarone "should be initiated and normally monitored only under hospital or specialist supervision". However, the responsibility for prescribing and monitoring maintenance therapy often falls to non-specialists. Here, we discuss safety issues relating to the long-term use of oral amiodarone in adults.

In 232 Japanese patients receiving long-term amiodarone therapy for life-threatening ventricular tachyarrhythmias, hyperthyroidism and hypothyroidism developed in 29 patients (12.5%) and 25 patients (10.8%), respectively. In patients with hyperthyroidism, the recurrence of sustained ventricular tachycardia was significantly higher with thyrotoxicosis than in the euthyroid period (31% vs 3%, p<0.01). Holter monitoring showed that the average heart rate and ventricular premature complexes significantly increased with hyperthyroidism. On the other hand, there was no increase in the recurrence of ventricular tachyarrhythmia with hypothyroidism. There was no change in the dose or the plasma concentration of amiodarone or desethylamiodarone in the euthyroid period or when hyperthyroidism or hypothyroidism manifested. It is important to monitor for arrhythmia when hyperthyroidism develops during amiodarone therapy.

Amiodarone hydrochloride is used in the treatment of ventricular and supraventricular arrhythmias. Because of its iodinated structure, thyroid dysfunction can occur during amiodarone therapy. The reported overall incidence is variable (2-24 per cent) and depends on several factors (past thyroid history, daily iodine intake,...). The present retrospective (1990-97) study was performed using the French pharmacovigilance database in order to compare the frequency of hypo- and hyperthyroidism in three areas in the South of France: Midi-Pyrénées, Aquitaine and Languedoc-Roussillon. For each case, the following data were recorded: age, sex, dysthyroidism history, dosage, duration and indication of amiodarone and delay to onset of dysthyroidism. We collected respectively 37, 50 and 9 cases of hypothyroidism in Midi-Pyrénées, Aquitaine and Languedoc-Roussillon and 20, 69 and 11 cases of hyperthyroidism respectively in the same areas. These data show the predominance of reported amiodarone-induced hyperthyroidism in Aquitaine and Languedoc-Roussillon. Hypothyroidism seems more frequent in Midi-Pyrénées, a non-maritime area. The sex ratio (male/female) was significantly different for the occurrence of hypothyroidism in Midi-Pyrénées (1.8 versus 0.5 in Aquitaine and 0.8 in Languedoc-Roussillon). The delay to onset of hypothyroidism was significantly shorter in Midi-Pyrénées (17.1 months +/- 24.5) when compared with Aquitaine (28.7 +/- 28.1) or Languedoc-Roussillon (43.4 +/- 45). Our results show an interregional difference in the occurrence of hypo/hyperthyroidism due to amiodarone.

Amiodarone, a benzofuranic-derivative iodine-rich drug used mostly for tachyarrhythmias, often causes changes in the peripheral metabolism of thyroid hormones mainly due to the inhibition of 5'-deiodinase activity: an increase in serum thyroxine and reverse triiodothyronine, and a decrease in serum triiodothyronine concentrations. Overt thyroid dysfunction, either amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH), occurring in 14% to 18% of patients receiving long-term treatment, may develop both in apparently normal thyroid glands and in glands with preexisting abnormalities. AIH is mainly due to the failure to escape from the acute Wolff-Chaikoff effect, and, in patients with thyroid autoimmune phenomena, to concomitant Hashimoto's thyroiditis. AIT is due to excess iodine-induced thyroid hormone synthesis (type I AIT) or to amiodarone-related destructive thyroiditis (type II AIT), although mixed forms often occur. Treatment of AIH consists of levothyroxine replacement therapy while continuing amiodarone therapy; alternatively, amiodarone can be discontinued, if possible, and the natural course toward euthyroidism can be accelerated by a short trial of potassium perchlorate. In type I AIT, the simultaneous administration of thionamides and potassium perchlorate is the treatment of choice, while in type II AIT steroids are the most useful therapeutic option. Mixed forms are best treated with a combination of thionamides, potassium perchlorate, and glucocorticoids. The low thyroidal 131I uptake usually makes radioiodine therapy not feasible, while thyroidectomy is a valid alternative in cases resistant to medical therapy.

Amiodarone is a benzofuranic-derivative iodine-rich drug widely used for the treatment of tachyarrhythmias and, to a lesser extent, of ischemic heart disease. It often causes changes in thyroid function tests (typically an increase in serum T(4) and rT(3), and a decrease in serum T(3), concentrations), mainly related to the inhibition of 5'-deiodinase activity, resulting in a decrease in the generation of T(3) from T(4) and a decrease in the clearance of rT(3). In 14-18% of amiodarone-treated patients, there is overt thyroid dysfunction, either amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH). Both AIT and AIH may develop either in apparently normal thyroid glands or in glands with preexisting, clinically silent abnormalities. Preexisting Hashimoto's thyroiditis is a definite risk factor for the occurrence of AIH. The pathogenesis of iodine-induced AIH is related to a failure to escape from the acute Wolff-Chaikoff effect due to defects in thyroid hormonogenesis, and, in patients with positive thyroid autoantibody tests, to concomitant Hashimoto's thyroiditis. AIT is primarily related to excess iodine-induced thyroid hormone synthesis in an abnormal thyroid gland (type I AIT) or to amiodarone-related destructive thyroiditis (type II AIT), but mixed forms frequently exist. Treatment of AIH consists of L-T(4) replacement while continuing amiodarone therapy; alternatively, if feasible, amiodarone can be discontinued, especially in the absence of thyroid abnormalities, and the natural course toward euthyroidism can be accelerated by a short course of potassium perchlorate treatment. In type I AIT the main medical treatment consists of the simultaneous administration of thionamides and potassium perchlorate, while in type II AIT, glucocorticoids are the most useful therapeutic option. Mixed forms are best treated with a combination of thionamides, potassium perchlorate, and glucocorticoids. Radioiodine therapy is usually not feasible due to the low thyroidal radioiodine uptake, while thyroidectomy can be performed in cases resistant to medical therapy, with a slightly increased surgical risk.

Although amiodarone is regarded as a highly effective anti-arrhythmic agent, its use may lead to alterations in thyroid gland function and/or thyroid hormone metabolism, partly because of its rich iodine content. Patients treated with amiodarone may manifest altered thyroid hormone profile without thyroid dysfunction, or they may present with clinically significant amiodarone-induced hypothyroidism or amiodarone-induced thyrotoxicosis. The former results from the inability of the thyroid to escape from the Wolff-Chaikoff effect. It prevails in areas with high dietary iodine intake, and it is readily managed by discontinuation of amiodarone or thyroid hormone replacement. Amiodarone-induced thyrotoxicosis occurs more frequently in areas with low iodine intake; it may arise from iodine-induced excessive thyroid hormone synthesis (type I) or destructive thyroiditis with release of preformed hormones (type II). Type I should be treated with thionamides alone or in combination with potassium perchlorate, whereas type II benefits from treatment with glucocorticoids. Surgery may be a feasible option for patients who require long-term amiodarone treatment.

Background: Amiodarone is widely used in adults with congenital heart disease, but no systematic study has been published on its effects on thyroid function in these patients. A retrospective study was performed to examine the frequency of amiodarone-associated thyroid dysfunction in adults with congenital heart disease and to identify any contributing factors., Methods and Results: All adults (16 to 60 years old) with congenital heart disease were identified from a database if they had no preexisting thyroid disease, had taken amiodarone for >/=6 months, and were currently followed up by 1 consultant (J.S.). Ninety-two patients were found and evaluated for thyroid status and cardiac complications. A case-control analysis was performed, with patients matched for duration of amiodarone therapy. Of the 92 patients (age, 34.9+/-10.2 years; range, 18 to 60 years), 36% developed thyroid dysfunction: 19 became hyperthyroid and 14 hypothyroid. Female sex and complex cyanotic heart disease were significant risk factors for developing thyroid dysfunction (odds ratios, 3.0 and 7.00; P=0.04 and 0.01, respectively). Previous Fontan-type surgery also appeared to be a risk factor for developing thyrotoxicosis (odds ratio, 4.0; P=0.17), and amiodarone >200 mg/d a risk factor for thyroid dysfunction (odds ratio, 4.0; P=0.60)., Conclusions: Amiodarone-associated thyroid dysfunction is common in adults with congenital heart disease. Women and those with complex cyanotic lesions are at particular risk, as patients may be who have had Fontan-type surgery or are taking >200 mg/d of amiodarone. Amiodarone should be used only when other antiarrhythmics are ineffective or contraindicated. Vigilance is required to detect and treat thyroid dysfunction.

Amiodarone may induce hyper- or hypothyroidism. Patients with beta-Thalassemia Major (beta-Thal) have an increased prevalence of primary hypothyroidism and often require amiodarone for hemosyderotic cardiomyopathy. Aim of this study was to retrospectively evaluate thyroid function in beta-Thal adult patients on long-term amiodarone. The study group consisted of twenty-two (21 males, 1 female; age: 23-36 yr) beta-Thal patients submitted to long-term (3-48 months) amiodarone therapy from January 1991 to July 1996. Controls included 73 beta-Thal patients (23 males and 50 females aged 25-35 yr) not treated with amiodarone. In all cases serum free thyroid hormones, thyrotropin and thyroid autoantibodies were evaluated. A higher prevalence of overt hypothyroidism (5/22 [22.7%]) as compared to controls (3/73 [4.1%], p=0.02) was found in beta-Thal patients < or = 3 months after starting amiodarone, while the prevalence of subclinical hypothyroidism was similar in amiodarone-treated (18.2%) and untreated (15%) beta-Thal patients. Overt hypothyroidism resolved spontaneously after amiodarone withdrawal in 1 case, while the remaining patients were maintained euthyroid on amiodarone by L-thyroxine administration. After 21-47 months of amiodarone therapy, 3 patients (13.6%) developed thyrotoxicosis (2 overt and 1 subclinical), which remitted shortly after amiodarone withdrawal. No case of hyperthyroidism was observed in beta-Thal controls (p=0.012 vs amiodarone-treated patients). In conclusion, amiodarone administration is often associated in adult beta-Thal patients to a rapid progression of the pre-existing subclinical hypothyroidism, but transient thyrotoxicosis may also be observed after a longer period of therapy. These findings should be carefully considered in the management of these patients.

Amiodarone is a highly effective antiarrhythmic agent. Its iodine content and tissue accumulation are however responsible for various side effects. In this article, we review the various amiodarone related side effects and propose a monitoring chart for patients treated by this specific agent.