Amiodarone-induced Hypothyroidism Research Articles

Amiodarone-induced thyroid dysfunction in Taiwan: a retrospective cohort study

The incidence and risk factors of amiodarone-induced thyroid dysfunction are variable in the literature. The aim of this study was to investigate the clinical and biochemical features and risk factors of amiodarone-induced thyroid dysfunction in Taiwan. This study was conducted at a tertiary referral center for arrhythmia. Retrospective analysis of patients treated with amiodarone during the years 2008-2009 was performed. Incidence and risk factors of amiodarone-induced thyrotoxicosis (AIT) and amiodarone-induced hypothyroidism (AIH) were assessed. Of the 527 patients, 437 (82.9 %) remained euthyroid, 21 (4.0 %) developed AIT, and 69 (13.1 %) were affected with AIH. In univariate analysis, AIT was associated with younger age, and the risk factors for AIH included older age, higher baseline thyroid stimulating hormone (TSH) titer, lower baseline free T4 level, lower cumulative amiodarone dosage, and shorter amiodarone treatment duration. Cox regression analysis was performed to determine the different risk categories in the elderly population of age 65-74 (young-old), 75-84 (old-old), and ≥85 years old (oldest-old). Additionally increased risk of AIH was found in the groups of old-old (HR 2.09, 95 % CI 1.11-3.96) and oldest-old (HR 2.57, 95 % CI 1.21-4.75). In the multivariate analysis of risk factors for AIH, baseline TSH level (HR 1.38, 95 % CI 1.12-1.70) and cumulative amiodarone dosage (HR 0.95, 95 % CI 0.93-0.97) remained statistically significant. AIH was much more common than AIT in Taiwan, an area with sufficient iodine intake. Higher baseline TSH level was the predominant independent risk factor for the development of AIH.

Incidence and Pattern of Thyroid Dysfunction in Patients on Chronic Amiodarone Therapy: Experience at a Tertiary Care Centre in Oman

Objective: To determine the incidence and pattern of thyroid dysfunction (TD) in patients on chronic amiodarone therapy. Methods: A retrospective study which evaluated 59 patients who had received amiodarone therapy regularly for at least 12 months from a period of 3 years from October 2007 to October 2010. The patients were followed-up at the cardiac clinic at Sultan Qaboos University Hospital, Muscat, Oman. Results: The mean age of the cohort was 63 ± 13 years ranging from 27 to 98 years. Fifty-one percent (n = 30) of the patients were female. There were 11 (19%) cases of thyroid dysfunction (TD). Seven (12%) patients were hypothyroid, 3 (5%) had hyperthyroidism and 1 (2%) patient had sub-clinical hypothyroidism; no cases of sub-clinical hyperthyroidism were noted. Female gender and presence of anti-thyroid peroxidase antibodies were significantly associated with amiodarone-induced hypothyroidism (p = 0.001) while age, amiodarone dose and duration of therapy were not correlated with the development of TD (all p-values > 0.05). Conclusion: Amiodarone-induced thyroid dysfunction is prevalent. Hypothyroidism was more frequent and seen more in female patients and those who had positive anti-thyroid peroxidase antibodies. Initial screening and periodic monitoring of thyroid function is mandatory for all patients on amiodarone therapy.

Amiodarone-Induced Thyroid Dysfunction

Amiodarone is an effective medication for the treatment of cardiac arrhythmias. Originally developed for the treatment of angina, it is now the most frequently prescribed antiarrhythmia drug despite the fact that its use is limited because of potential serious side effects including adverse effects on the thyroid gland and thyroid hormones. Although the mechanisms of action of amiodarone on the thyroid gland and thyroid hormone metabolism are poorly understood, the structural similarity of amiodarone to thyroid hormones, including the presence of iodine moieties on the inner benzene ring, may play a role in causing thyroid dysfunction. Amiodarone-induced thyroid dysfunction includes amiodarone-induced thyrotoxicosis (AIT) and amiodarone-induced hypothyroidism (AIH). The AIT develops more commonly in iodine-deficient areas and AIH in iodine-sufficient areas. The AIT type 1 usually occurs in patients with known or previously undiagnosed thyroid dysfunction or goiter. The AIT type 2 usually occurs in normal thyroid glands and results in destruction of thyroid tissue caused by thyroiditis. This is the result of an intrinsic drug effect from the amiodarone itself. Mixed types are not uncommon. Patients with cardiac disease receiving amiodarone treatment should be monitored for signs of thyroid dysfunction, which often manifest as a reappearance of the underlying cardiac disease state. When monitoring patients, initial tests should include the full battery of thyroid function tests, thyroid-stimulating hormone, thyroxine, triiodothyronine, and antithyroid antibodies. Mixed types of AIT can be challenging both to diagnose and treat and therapy differs depending on the type of AIT. Treatment can include thionamides and/or glucocorticoids. The AIH responds favorably to thyroid hormone replacement therapy. Amiodarone is lipophilic and has a long half-life in the body. Therefore, stopping the amiodarone therapy usually has little short-term benefit.

The Characteristics of Amiodarone-induced Thyrotoxicosis in a Moderate Iodine Deficit Area

Abstract Introduction: Amiodarone (AMI), a class III anti-arrhythmic drug, is associated with a number of side effects, including thyroid dysfunction (both hypo- and hyperthyroidism), which is due to amiodarone's high iodine content and its direct toxic effect on the thyroid. Objective: To evaluate the incidence of Amiodarone induced thyrotoxicosis (AIT) (type, rate of occurrence) and to identify the risk factors involved in its occurrence. Material and method: We examined patients treated with amiodarone, between January 2002 and December 2011, who presented to our Department of Endocrinology Târgu Mures for thyroid dysfunctions. Results: The retrospective study included 87 patients with thyroid dysfunctions; 58 (66.7%) patients had AIT and 29 (33.3%) had Amiodarone induced hypothyroidism (AIH). In the AIT group: 35 were women (60.3%), 23 were men (39.7%); the average age was 61.60 ± 12.39 years. Risk factors identified for the AIT group were male gender (RR = OR = 3.8; Chi-squer = 5.7, p = 0.004) and pre-existing thyroid abnormalities (RR = 2.5, Chi-square = 4.1, p = 0.005). The thyroid dysfunction occurrence was heterogeneous (0.2-183 months). The patients with previous thyroid abnormalities developed earlier thyroid dysfunction compared to those with an apparently normal thyroid gland (22.25 ± 4.14 months versus 32.09 ± 7.69 months, p = 0.02, T test). Conclusion: In the context of the specific iodine geoclimatic intake and the area of origin, amiodarone - induced thyroid dysfunction spectrum is dominated by thyrotoxicosis. Screening and monitoring of thyroid function for patiens under chronic amiodarone treatment is necessary

Amiodarone and the thyroid dysfunction

Amiodarone, a class III antiarrhytmic agent, is a benzofuran derivative containing 75 mg iodide per 200 mg tablet. During the metabolism of 200 mg of the drug approximately 6-8 mg of inorganic iodine is released into the systemic circulation. Amiodarone is very lipophilic and concentrates in various tissues and organs such as adipose tissue, skeletal muscles, myocardium, liver, lung and thyroid. Amiodarone is dealkylated in the liver to its major active metabolite desethylamiodarone. Amiodarone therapy is associated with a number of side effects, including thyroid dysfunction – thyrotoxicosis in 2-15% and hypothyroidism in 5-20% of patients, respectively. The effects of amiodarone on thyroid function depend on underlying thyroid status and dietary iodine intake. Patients with autoimmune thyroid disease are more likely to develop hypothyroidism due to failure to escape from Wolff-Chaikoff effect. In patients with multinodular goiter or latent Graves’ disease hyperthyroidism may occur. Amiodarone may also cause destructive thyroiditis in patients without underlying thyroid disease. Thyrotoxicosis may be a result of increased synthesis of thyroid hormones (type 1) or of their excessive release due to a direct damage of thyroid cells caused by amiodarone, its metabolite desethylamiodarone or iodine (type 2). The distinction between type 1 and type 2 thyrotoxicosis is crucial, since therapy is different in these two types. The differential diagnosis is based on the presence of goiter, evaluation of thyroid autoantibodies, colour flow Doppler image, thyroid uptake and on the response to steroids or perchlorate. Patients with type 1 thyrotoxicosis require thionamides or potassium/sodium perchlorate, while those with type 2 – corticosteroids. Hypothyroidism is treated with L-thyroxine. The signs and symptoms of amiodarone-induced thyrotoxicosis and hypothyroidism can be scanty. Therefore, all patients treated with amiodarone need periodic examination of thyroid function. Apart from inducing thyroid dysfunction, amiodarone causes hypercholesterolemia due to decreased expression of the LDL receptor gene, which is regulated by T3. Adverse effects of amiodarone have led to the search for analogues with the same efficacy but safer profile. Dronedarone is structurally related to amiodarone but does not contain iodine atoms and does not increase the incidence of thyroid disease. Dronedarone appears to be less-effective but may be beneficial for patients with atrial fibrillation or flutter who are at risk of developing amiodarone induced thyroid dysfunction.

Disfunção tiróidea e amiodarona

Although most patients remain clinically euthyroid, some develop amiodarone-induced hyperthyroidism (HPEAI) or hypothyroidism (HPOAI). The authors present a retrospective analysis of ten patients with amiodarone-induced thyroid dysfunction. Six patients were female and mean amiodarone intake was 17.7 months. HPOIA was more common (six patients). From all the patients with HPEAI, two had type 2, one had type 1, and one had type 3 hyperthyroidism. Symptoms suggestive of thyroid dysfunction occurred in five patients, most of them with HPOAI. In HPEAI, the most frequent symptom was exacerbation of arrhythmia (three patients). Discontinuation of amiodarone and treatment with levothyroxine was chosen in 83.3% of the HPOAI cases, while thyonamide treatment with corticosteroids and without amiodarone was the option in 75% of the HPEAI cases. There were three deaths, all in patients with HPEAI. HPEAI is potentially fatal. The clinical picture may be vague, so the thyroid monitoring is mandatory.

Letter to the Editor Amiodarone-induced thyrotoxicosis with paroxysmal supraventricular (ectopic atrial) tachycardia: and review of the literature

Letter to the Editor Amiodarone-induced thyrotoxicosis with paroxysmal supraventricular (ectopic atrial) tachycardia: and review of the literature

A Case of Simultaneously Occurred Amiodarone-induced Hepatitis and Hypothyroidism

Amiodarone is a di-iodated benzofuran derivative that is commonly used to treat patients with various cardiac arrhythmias. It is associated with side effects that involve the liver, thyroid, and other organs. Approximately 1-3% of patients treated with amiodarone suffer from symptomatic liver disease. Thyroid dysfunction occurs in 10% of patients treated with amiodarone. A 65-year-old woman with coronary heart disease and atrial fibrillation was administered with amiodarone. She developed nausea, vomiting, dyspepsia, and sweating within 9 months of amiodarone administration (200 mg orally once a day). Results of the laboratory finding showed increased hepatic enzymes, and low thyroid hormone levels. A liver biopsy showed irregular arrangement of hepatocytes and diffuse micro- and macrovesicular fatty changes. Electron microscopy findings showed pleomorphic mitochondria with crystalloid inclusions and membrane-bound lysosomal structures. The liver and thyroid functions returned to normal, after the amiodarone was stopped. We describe an unusual case in which amiodarone induced hepatitis and hypothyroidism simultaneously. Physicians should take a close look to the adverse event when using amiodarone which can cause adverse effects in multiple organs.

Amiodarone-Induced Thyrotoxicosis Late After Amiodarone Withdrawal

Amiodarone-induced thyrotoxicosis (AIT) may develop long after amiodarone withdrawal. This study sought to determine the incidence and clinical characteristics of AIT after amiodarone withdrawal. The incidence and clinical characteristics of AIT were examined retrospectively in 71 patients (51 males, mean age 65±13 years) whose amiodarone therapy had been discontinued after at least 1 month of administration. Five (7%) patients developed AIT late after amiodarone withdrawal (11±3 months): 2 patients exhibited exacerbation of heart failure by atrial fibrillation, 2 developed dyspnea on exertion, and 1 patient was asymptomatic. The patients who developed AIT had a high incidence of amiodarone-induced hypothyroidism during amiodarone therapy (100 vs. 24%, P=0.002), had received amiodarone therapy for longer (76±86 months vs. 16±22 months, P<0.001), with a larger cumulative dose (271.1±268.5 g vs. 63.4±86.5 g, P<0.001) compared with those who did not. In all 5 patients, AIT resolved spontaneously within 5 months without the use of steroids. Occurrence of amiodarone-induced hypothyroidism during amiodarone therapy and long duration of therapy may be cautionary markers of late AIT.

Development of Refractory Ascites during Amiodarone Therapy in a Hemodialysis Patient with Nephrogenic and Cardiogenic Ascites

In this report, the clinical characteristics of a 65-year-old female patient with tricuspid regurgitation, ischemic cardiomyopathy, congestive heart failure, and chronic renal failure were retrospectively evaluated. Laboratory studies revealed cardiogenic ascites coincided with nephrogenic ascites and subclinical amiodarone-induced hypothyroidism. The ascites of the patient was responsive to management of congestive heart failure and therapeutic paracentesis during the first episode, add-on therapy with intensified hemodialysis during the second episode, and add-on therapy with low-dose eltroxin during the third episode. When nephrogenic ascites and cardiogenic ascites of maintenance hemodialysis patients become refractory, hypothyroidism should be examined in these patients.

Recognizing amiodarone-induced hypothyroidism

Amiodarone is often prescribed for ventricular and atrial dysrhythmias. The signs and symptoms of amiodarone-induced hypothyroidism (AIH) can be missed or misdiagnosed in a patient with a complex clinical condition. Here's what you need to know.

Amiodarone and the thyroid: a 2012 update.

Amiodarone-induced thyroid dysfunction occurs in 15-20% of amiodarone-treated patients. Amiodarone-induced hypothyroidism (AIH) does not pose relevant problems, is easily controlled by L-thyroxine replacement, and does not require amiodarone withdrawal. Most frequently AIH develops in patients with chronic autoimmune thyroiditis. Amiodarone- induced thyrotoxicosis (AIT) is most frequently due to destructive thyroiditis (type 2 AIT) causing discharge of thyroid hormones from the damaged, but otherwise substantially normal gland. Less frequently AIT is a form of hyperthyroidism (type 1 AIT) caused by the iodine load in a diseased gland (nodular goiter, Graves' disease). A clearcut differentiation between the two main forms is not always possible, despite recent diagnostic advances. As a matter of fact, mixed or indefinite forms do exist, contributed to by both thyroid damage and increased thyroid hormone synthesis. Treatment of type 1 (and mixed forms) AIT is based on the use of thionamides, a short course of potassium perchlorate and, if treatment is not rapidly effective, oral glucocorticoids. Glucocorticoids are the first-line treatment for type 2 AIT. Amiodarone should be discontinued, if feasible from a cardiac standpoint. Continuation of amiodarone has recently been associated with a delayed restoration of euthyroidism and a higher chance of recurrence after glucocorticoid withdrawal. Whether amiodarone treatment can be safely reinstituted after restoration of euthyroidism is still unknown. In rare cases of AIT resistance to standard treatments, or when a rapid restoration of euthyroidism is advisable, total thyroidectomy represents a valid alternative. Radioiodine treatment is usually not feasible due to the low thyroidal iodine uptake.

Amiodarone-induced hypothyroidism presenting as cardiorenal syndrome.

Here we present the case of a 90-year-old man with chronic heart and renal failure who was admitted with what appeared to be a simple heart failure exacerbation. However, further investigation led to the diagnosis of profound amiodarone-induced hypothyroidism as the cause of his acute decompensation, highlighting the importance of a broad differential diagnosis and thorough investigation.

'False-positive' intrathoracic impedance monitor alarm caused by amiodarone-induced hypothyroidism in a patient with cardiac resynchronization therapy-defibrillator

A 78-year-old female received a cardiac resynchronization therapy-defibrillator equipped with an intrathoracic impedance (ITI) monitor and amiodarone therapy was initiated. A massive and long-lasting decrease in ITI occurred without heart failure (HF) deterioration. Pericardial effusion secondary to amiodarone-induced hypothyroidism may have caused the impedance reduction.

Thyroxine monotherapy without amiodarone enhances atrial fibrillation recurrences in amiodarone-induced hypothyroidism

Atrial fibrillation (AF) is the most sustained cardiac arrhythmia requiring medical care. Amiodarone is a di-iodinated benzofuran derivative widely used for preventing the recurrences of AF [1]. Although amiodarone is the most effective agent in rhythm control of AF [2], the adverse effects of amiodarone frequently result in treatment discontinuations. Hypothyroidism caused by the iodine in amiodarone is one of the most frequent and important adverse effects. The incidence of amiodarone-induced hypothyroidism varies from 1 to 32% [3–7].

A Rare Case of Amiodarone-Induced Hypothyroidism Presenting with Cardiac Tamponade

Subclinical pericardial effusions are common in patients with untreated hypothyroidism and usually resolve with thyroid replacement therapy, but cardiac tamponade is a rare presentation of prolonged untreated hypothyroidism. We report the first case of cardiac tamponade due to hypothyroidism produced by administration of amiodarone.

Management of amiodarone-related thyroid problems

Amiodarone is a highly effective and well-established antiarrrhythmic drug. It can be used to treat supraventricular and ventricular tachyarrhythmias and has the added advantage of being well tolerated in patients with impaired left ventricular systolic function with a low incidence of arrhythmic events, such as torsades de pointes. However, owing to its marked lipid affinity, it is highly concentrated in tissues and is linked to a number of adverse effects, including thyroid dysfunction. Amiodarone can lead to both hypothyroidism (amiodarone-induced hypothyroidism) and less commonly hyperthyroidism (amiodarone-induced thyrotoxicosis) and relates to high iodine content within the molecule as well as to several unique intrinsic properties of amiodarone. Dronedarone is a recently approved antiarrhythmic drug. It is structurally very similar to amiodarone, however the iodine moiety, present with amiodarone has been removed and replaced with a methylsulfonamide group to reduce fat solubility and adverse effects. We present an overview of the effects of amiodarone on thyroid function and the treatment options available, as well as a brief insight into dronedarone and its potential as an alternative to amiodarone.

Amiodarone-Induced Hypothyroidism and Other Adverse Effects

Amiodarone is a class III antiarrhythmic agent that is frequently prescribed today for the treatment of ventricular and atrial arrhythmias. Amiodarone has many adverse effects, and one of them is thyroid dysfunction. Advanced practice and staff nurses need to be vigilant, recognizing early signs and symptoms of thyroid dysfunction to prevent adverse drug reactions. Often, the signs and symptoms of amiodarone-induced hypothyroidism are overlooked because of the complexity of the patient's condition. The purpose of this article was to review a case study, present differential diagnoses and testing, discuss risk factors associated with amiodarone-induced hypothyroidism, discuss its pathogenesis, and review clinical management.

Severe amiodarone-induced hypothyroidism in an infant

To report a case of postnatal, postoperative amiodarone-induced hypothyroidism in an infant with a congenital heart defect. Case report and literature review. Pediatric intensive care unit at a freestanding tertiary care children's hospital. At 7 wks of age, a female infant with a congenital heart defect was confirmed to have profound hypothyroidism after amiodarone administration for a postoperative cardiac arrhythmia. Levothyroxine treatment. Thyroid function tests were regularly performed to guide levothyroxine dosing. Thyroid hormone replacement was discontinued after the infant had been off amiodarone for 6 mos. Given the potential adverse developmental consequences associated with hypothyroidism during infancy and early childhood, thyroid function tests should be carefully monitored in any infant treated with amiodarone.

Intrathoracic Impedance Monitoring Uncovered Presymptomatic Amiodarone-Induced Hypothyroidism: Another Possible Cause of Impedance Drop

Intrathoracic impedance (ITI), measured between the right ventricular coil and the device can, reflects intrathoracic fluid status. A 78-year-old female with dilated cardiomyopathy who survived cardiopulmonary arrest received a cardiac resynchronization therapy-defibrillator equipped with an ITI monitor. She had been prescribed amiodarone since November 2008. The ITI began to decrease steadily since September 2009 without worsening of heart failure symptoms. She was relatively well until December 2009 when she became aware of swelling of the face and lower legs. She noticed increasing easy fatigability and weakness in February 2010 and entered the hospital. A chest X-ray film showed an increase in the size of the heart shadow without worsening of pulmonary congestion or pleural effusions. An echocardiogram revealed a large pericardial effusion. The free thyroxin was 0.05 ng/dL, the free triiodothyronine 0.42 pg/mL, and the TSH 200.4 µIU/mL. These findings were consistent with a diagnosis of amiodarone-induced hypothyroidism. She was treated with levothyroxine, along with dose reduction of amiodarone. All symptoms improved gradually and the ITI began to increase since March 2010 and finally restored to the baseline level in September when the pericardial effusion almost disappeared and thyroid hormone test returned to normal. Our case suggests that ITI monitoring could uncover presymptomatic amiodarone-induced hypothyroidism possibly by detecting pericardial effusions.