Amiodarone-induced Hypothyroidism Research Articles

Potential use of pharmacogenetics in cardiology: genome-wide association studies of amiodarone-induced thyroid disorders

Abstract Background Amiodarone is a commonly prescribed antiarrhythmic drug used to manage supraventricular and ventricular arrhythmias. The use of amiodarone is associated with a broad range of adverse effects, including amiodarone-induced hypothyroidism (AIH) or amiodarone-induced thyrotoxicosis (AIT) (1). Both conditions are linked with increased mortality and have no known reliable risk predictors (2). Purpose We investigated the genetic underpinnings of amiodarone-induced thyroid disorders, and the clinical validity and utility of screening for genetic variants. Methods We conducted the first genome-wide association studies (GWAS) of AIH and AIT using data from three large biobanks. We compared the AUCs for SNPs identified through the above GWAS with polygenic risk scores for both hypo- and hyperthyroidism. Finally, we tested the clinical validity and utility of screening for risk variants. Results We found two risk loci for AIH. The lead variant at the first locus, rs1443438, was intronic to FOXE1 (OR 0.39, MAF = 35%, P = 1.59 × 10-42). The other lead variant, rs2209796, was located 93 kb upstream to FOXA2 (OR 0.56, MAF = 29%, P = 2.64 × 10-15: Figure 1). For AIT, we found one risk locus. The lead variant, rs2268803, was intronic to CAPZB (OR 1.81, MAF = 42%, P = 2.43 × 10-8: Figure 1). Next, we added GWAS SNPs or polygenic risk scores to risk prediction models consisting of age, sex and 4 principal components (PCs), and compared AUC estimates between risk models. Using GWAS SNPs, we found that the AIT variant increased the AUC with 6% (95%CI 1.1 – 10.3, AUC: 0.72) and 9% (95%CI 6.2 – 11.2, AUC: 0.75) for AIH, compared to the benchmark model. Both GWAS SNP models were superior to polygenic risk scores in terms of AUC (P for difference <0.05). The positive and negative predictive value (PPV and NPV) for the AIT-variant was 14.6% and 95.7%, respectively. For the AIH-variants combined, we found a PPV of 17% and a NPV of 95%. Conclusions Common genetic variants are associated with both amiodarone-induced hypo- and hyperthyroidism and are at this point, superior to polygenic risk scores in predicting amiodarone-induced thyroid disorders. These findings add to the potentials of pharmacogenetics in cardiology. Figure 1. Double Manhattan plot of amiodarone induced thyroid disorders. The Y-axis is the negative log10 of the P-value for each single nucleotide polymorphism. The X-axis is the chromosome, with positions on each chromosome ranging from lower to higher (left to right). The dotted line marks the threshold for genome-wide significance. Amiodoarone-induced hypothyroidism at the top, and amiodarone-induced thyrotoxicosis at the bottom.Figure 1

Amiodarone-induced hypothyroidism: from myxedema coma to euthyroidism

Amiodarone-induced hypothyroidism: from myxedema coma to euthyroidism

Monitoring thyroid function during amiodarone use.

Amiodarone is an antiarrhythmic drug used to treat cardiac tachyarrhythmias. It has many adverse effects, with thyroid dysfunction one of the most notable. Through various mechanisms, both thyrotoxicosis and hypothyroidism can occur secondary to amiodarone therapy. There are two types of amiodarone-induced thyrotoxicosis: type 1 occurs in those with pre-existing thyroid disease and is treated with thionamide, whereas type 2 occurs in those without and is treated with glucocorticoids. Patients with amiodarone-induced hypothyroidism may be given levothyroxine to replace thyroid hormone, but in some cases, the appropriate management may be cessation of amiodarone.

An uncommon side effect: amiodarone-related hypothyroidism in a patient with negative thyroid autoantibodies.

Amiodarone is an antiarrhythmic drug frequently used in cardiac dysrhythmias. One of the most important side effects of amiodarone is thyroid dysfunction. Amiodarone-induced thyrotoxicosis (AIT) and amiodarone-induced hypothyroidism (AIH) can occur depending on individuals' iodine status and previous thyroid disease. In this case, we aimed to present the hypothyroidism that developed in a patient with negative thyroid autoantibodies after amiodarone use.

Genome-wide association study of amidoarone-induced hypothyroidism

Abstract Background Amiodarone is a commonly prescribed antiarrhythmic drug used to manage supraventricular and ventricular arrhythmias. The use of amiodarone is associated with a broad range of adverse effects across several organ systems. As many as 10-20% of all patients treated with amiodarone develop thyroid dysfunction, most commonly amiodarone induced hypothyroidism (AIH). (1) Purpose We examined if AIH may have a genetic predisposition. Methods We conducted the first genome-wide association study of AIH using data from a large biobank. Cases were defined as individuals who within one year of amiodarone initiation were given a diagnosis of hypothyroidism or treated with thyroid hormone replacement. Controls were defined as individuals who were continuously treated with amiodarone, without any history of hypothyroidism. Odds Ratios (ORs) and 95% confidence intervals (CIs) were computed using logistic mixed model regression. Results In total, we identified 339 cases of AIH and 2,296 amiodarone-treated controls (Table 1). We found two risk loci, residing at chromosome 9q22.33 and 20p11.21. The lead variant at the first locus, rs9696968-G, was an intron variant located in PTCSC2 (OR: 2.32; 95% CI 1.91 – 2.83, P = 8.17 × 10-18). The other lead variant, rs1543443-A, was located 82 kb upstream to FOXA2 and was at borderline genome-wide significance (OR 1.77, 95% CI 1.44 – 2.19, P = 5.19 × 10-8; Figure 1). The locus in PTCSC2 is a top hit in thyroid cancer (OR 1.69) and hypothyroidism (OR 1.3). (2) FOXA2, a critical transcription factor, is recognized in mice for its role during development, in regulation of mature tissues, and once mutated also involved in cancer. (3) Conclusions We found two risk loci located in PTCSC2 and FOXA2 that were significantly associated with AIH, but replication is needed in order to confirm these associations. Indeed, it seems that individuals with genetic susceptibility to hypothyroidism are more likely to develop AIH, hence the PTCSC2 locus is a known high impact rick locus for hypothyroidism. These findings add to the potentials of pharmacogenetics in cardiology. Cases are individuals with hypothyroidism within one year after initiation of amiodarone therapy. Controls are disease free individuals who are continuously taking amiodarone. The Y-axis is the negative log10 of the P-value for each single nucleotide polymorphism. The X-axis is the chromosome, with positions on each chromosome ranging from lower to higher (left to right). Each novel locus is presented in red color. The dotted line marks the threshold for genome-wide significance.Table 1.Characteristics of study group.Figure 1.Manhattan plot of amiodarone induced hypothyroidism.

FRI502 Myxedema Coma With An Unusual Pattern Of Thyroid Function Tests Due To Amiodarone-induced Hypothyroidism

Abstract Disclosure: S. Nguyen: None. B. Force: None. R. Schneider Aguirre: None. Introduction: Myxedema coma is an endocrine emergency characterized by severe hypothyroidism resulting in altered mental status or coma, hypothermia, cardiovascular compromise, pulmonary edema or pleural effusions, and/or gastrointestinal hypomotility, classically in the context of an elevated TSH and low thyroxine levels. Amiodarone use is associated with alteration of thyroid function tests and could cloud the laboratory presentation of myxedema coma. Here we present a case of myxedema coma in a patient with amiodarone-induced hypothyroidism with an elevated free T4 (FT4) and low total T3 (TT3). Clinical Case: A 64-year-old female with a history of chronic systolic heart failure, persistent atrial flutter treated with amiodarone, cerebrovascular accident, hypertension, chronic kidney disease stage 4, but not hypothyroidism, presented with constipation, confusion and lethargy worsening over 3 days. On initial evaluation, she was minimally responsive, hypothermic to 95.6 °F and bradycardic to low 50s. She was intubated for airway protection and vasopressors were started due to concern for cardiogenic shock. Exam was notable for coarse facial features, edema and cold extremities. A bedside echocardiogram showed reduced cardiac function from baseline. Her TSH was 40.65 uIU/mL (RR, 0.45-5.33 uIU/mL), FT4 1.79 ng/dL (RR 0.64-1.42 ng/dL), total T4 14.30 mcg/dL (RR 6.09-12.23 mcg/dL), TT3 70 ng/dL (RR 87-178 70 ng/dL). Sodium was 135 mmol/L (RR 136-145 mmol/L), serum glucose was 42 mg/dL, (RR 70-110 mg/dL), and eGFR was 18 mL/min/1.73 m2 (baseline eGFR 28 mL/min/1.73 m2). Evaluations for myocardial infarction and infectious etiology were initiated and ultimately negative. While elevated FT4 is not characteristic of myxedema coma, the overall constellation of stupor, constipation, bradycardia, hyponatremia, hypoglycemia, decreased eGFR and decreased cardiac function, in the setting of an elevated TSH and low TT3, made the diagnosis of myxedema coma extremely likely. The patient was started on levothyroxine 200 mcg IV daily and hydrocortisone 100 mg IV every 8 hours. After 16-20 hours on this regimen, the patient was weaned off sedation and vasopressors, extubated, and recovered baseline mental status. Hydrocortisone was stopped and on day 3 of hospitalization, she was transitioned to oral levothyroxine 88 mcg daily. Due to premature ventricular contractions her dose was decreased to 50 mcg orally daily five days after her initial presentation to the hospital. During this time, the TSH decreased to 3.59 uIU/mL and the FT4 rose to 2.83 ng/dL. Conclusion: We conclude that in patients treated with amiodarone, myxedema coma can still occur even if T4 levels are normal or elevated, likely due to decreased T4 to T3 conversion. In these cases, elevated TSH and a clinical picture consistent with severe hypothyroidism are more reliable indicators if the (free) T4 levels are unexpectedly elevated. Presentation: Friday, June 16, 2023

SAT504 Thyroidal Pax de Deux: 2 Cases of Resistance to Thyroid Hormone and Coexisting Thyroid Disease

Abstract Disclosure: S.V. Ribeiro: None. T. Moreno: None. A. Varela: None. P. Freitas: None. D.M. Carvalho: None. Resistance to thyroid hormone (RTH) is a rare clinical syndrome defined by hyposensitivity to thyroid hormone (TH) and characterized by elevated TH levels in the absence of TSH suppression. In most subjects with RTH, treatment is not required as tissue resistance is adequately compensated for by an increase in the endogenous supply of TH. This is not the case in patients with limited thyroidal reserve. Here we describe the clinical features of two unrelated patients with RTH and coexisting thyroid disease. Patient 1 was an 18-year-old female medical student referred to our consultation from Pediatrics. She had been diagnosed with autoimmune thyroiditis at age of 7 following the development of an obvious goiter. By then her thyroid-function tests (TFT) showed elevated TSH (8.75 µIU/mL, NR 0.41-3.67) and a normal free T4 (1.3 ng/dL, NR 0.82-1.76). She tested positive for the presence of antibodies to thyroperoxidase and thyroglobulin. The cytological findings on aspiration biopsy were consistent with Hashimoto’s thyroiditis. Throughout the years, despite levothyroxine supplementation she displayed systematically elevated TSH and normal FT4. The results of a thyrotropin stimulation test were normal. The suspicious of erratic compliance to therapy was raised.Follow-up at our outpatient clinic confirmed requirement for unusually high replacement doses of levothyroxine in order to maintain TSH within normal limits at expense of elevated FT4 and FT3 levels, suggesting the possibility of RTH. She was found with a THRβ c.1292T>C p.(Iso431Thr) heterozygous mutation. She remains clinically euthyroid under supplementation. Patient 2 was an asymptomatic 54-year-old female who consulted us for further evaluation of a thyroid nodule. Thyroid-FT showed an elevated FT3, at 3.86 μg/dL (NR, 1.75 to 3.71), an elevated FT4 at 1.86 ng/dL (NR 0.70 to 1.48), and a normal TSH level at 1.55 µIU/mL (NR, 0.40 to 4.50). A diffuse goiter was revealed by scintigraphy and the ultrasound showed no relevant findings. A diagnosis of RTH was genetically confirmed (THRβ c.1707C>G p.(P453A)). After a 6-year follow-up, she was diagnosed with supraventricular tachyarrhythmia for which she was started on amiodarone. Shortly after, her TFT revealed elevated TSH that normalized a few months after amiodarone withdrawal. Three years later, she was admitted to the intensive care unit due to cardiogenic shock attributed to tachycardia-induced cardiomyopathy and restarted on amiodarone. Her subsequent TFT showed elevated TSH (42.07 µIU/mL), with decreasing levels of TH (FT3 2.02 μg/dL, FT4 1.06 ng/dL). A diagnosis of amiodarone-induced hypothyroidism was made and levothyroxine supplementation was initiated and adjusted considering the patient’s symptoms. These cases show that the coexistence of RTH with other thyroidal disease can make diagnosis and management challenging and requires awareness and long-term follow-up. Presentation Date: Saturday, June 17, 2023

DUOX1 Gene Missense Mutation Confers Susceptibility on Type 2 Amiodarone-Induced Thyrotoxicosis.

Possible triggers and genetic markers involved in pathogenesis of amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH) are currently unknown. This study aimed to analyze the association between polymorphisms in the genes involved in thyroid hormones biosynthesis and metabolism. Thirty-nine consecutive patients with confirmed type 2 amiodarone-induced thyrotoxicosis were enrolled; 39 patients on the same therapy for at least 6 months without thyroid pathology were included as a control group. A comparative study was carried out to determine the distribution and genotypes of polymorphic markers of the (Na)-iodide symporter (NIS) genes (rs7250346, C/G substitution), thyroid stimulating hormone receptor (TSHR) (rs1991517, C/G substitution), thyroid peroxidase (TPO) (rs 732609, A/C substitution), DUOX 1-1 (C/T substitution), DUOX 1-2 (G/T substitution), DUOX 1-3 (C/T substitution), glutathione peroxidase 3 (GPX3) (C/T substitution), glutathione peroxidase 4 (GPX4) (C/T substitution). Statistical analysis was performed using Prism (Version 9.0.0 (86)). This study showed that the risk of AIT2 is 3.18 times higher in the G/T of the DUOX1 gene carriers. This study is the first report of genetic markers associated with amiodarone-related adverse events conducted in humans. The obtained results indicate the necessity for a personalized approach to amiodarone administration.

Protective Effects of Alfa Lipoic Acid on Amiodarone Induced Hypothyroidism in Adult Male Albino Rats (A Biochemical, Histopathological and Immunohistochemical Study)

Protective Effects of Alfa Lipoic Acid on Amiodarone Induced Hypothyroidism in Adult Male Albino Rats (A Biochemical, Histopathological and Immunohistochemical Study)

AMIODARONE AND THYROID DYSFUNCTION.

Thyroid gland has a key role in maintaining the body homeostasis. Thyroxine is the main hormone secreted from the thyroid gland, its effect being predominantly achieved after the intracellular conversion of thyroxine to triiodothyronine, which exhibits a higher affinity for the receptor complex, thus modifying gene expression of the target cells. Amiodarone is one of the most commonly used antiarrhythmics in the treatment of a broad spectrum of arrhythmias, usually tachyarrhythmias. Amiodarone contains a large proportion of iodine, which is, in addition to the intrinsic effect of the medication, the basis of the impact on thyroid function. It is believed that 15%-20% of patients treated with amiodarone develop some form of thyroid dysfunction. Amiodarone may cause amiodarone-induced hypothyroidism (AIH) or amiodarone-induced thyrotoxicosis (AIT). AIT is usually developed in the areas with too low uptake of iodine, while AIH is developed in the areas where there is a sufficient iodine uptake. Type 1 AIT is more common among patients with an underlying thyroid pathology, such as nodular goiter or Graves' (Basedow's) disease, while type 2 mostly develops in a previously healthy thyroid. AIH is more common in patients with previously diagnosed Hashimoto's thyroiditis. Combined types of the diseases have also been described. Patients treated with amiodarone should be monitored regularly, including laboratory testing and clinical examinations, to early detect any deviations in the functioning of the thyroid gland. Supplementary levothyroxine therapy is the basis of AIH treatment. In such cases, amiodarone therapy quite often need not be discontinued. Type 1 AIT is treated with thyrostatic agents, like any other type of thyrotoxicosis. If possible, the underlying amiodarone therapy should be discontinued. In contrast to type 1 AIT, the basic pathophysiological substrate of which is the increased synthesis and release of thyroid hormones, the basis of type 2 AIT is destructive thyroiditis caused by amiodarone, desethylamiodarone as its main metabolite, and an increased iodine uptake. Glucocorticoid therapy is the basis of treatment for this type of disease.

The effects of amiodarone on thyroid function in pediatric and adolescent patients.

Amiodarone-induced thyroid dysfunction is well established. The present review discusses recent literature related to the effects of amiodarone on the thyroid gland and thyroid function in pediatrics. Current guidelines in adults treated with amiodarone recommend baseline thyroid function testing followed by initiation of thyroid hormone monitoring after 3 months on therapy. Two retrospective studies to evaluate amiodarone-induced thyroid dysfunction in children and young adults reveal thyroid dysfunction as soon as 2 weeks after amiodarone initiation with a greater percentage of pediatric patients developing amiodarone-induced hypothyroidism rather than thyrotoxicosis. Although additional studies are needed to determine if AIH is associated with negative impact on growth and neurocognitive development, what is clear is that in both adults and pediatrics, there is low compliance with recommended side effect-monitoring guidelines. Pediatric patients are at similarly high risk to develop amiodarone-induced thyroid dysfunction as are adults. It is hoped that through improved education of providers and patients further research into the incidence, the potential risks of amiodarone therapy and the potential benefits of thyroid hormone replacement therapy in patients with AIH will be investigated and reported.

Amiodarone-Induced Hypothyroidism Initially Presenting as Decompensated Heart Failure and Hyponatremia

Introduction: Amiodarone is an effective antiarrhythmic, but it is associated with altering thyroid function, ranging from thyrotoxicosis to hypothyroidism. In this study, we discuss amiodarone-induced hypothyroidism (AIH) presenting with hyponatremia and myxedema. Case Presentation: A 75-year-old Caucasian man with a history of ischemic heart disease with an ejection fraction of 55-60% was seen in the ED with complaints of worsening lower limb edema and shortness of breath. Associated symptoms of constipation, generalized weakness, daytime sleepiness, and increased urinary frequency were noted. He was recently diagnosed with atrial fibrillation with a CHA₂DS₂-Vasc score of 5 and started on amiodarone nine months ago. He weighed 235 lbs with a BMI of 33.85 and vital signs are as follows: blood pressure 90/64, heart rate 64, respiration rate 13, and a temperature of 36.6 °C. Physical examination revealed a well-developed man in mild distress and slightly lethargic, with a palpable thyroid gland, heart sounds revealed an irregularly irregular heart rate, elevated JVD, bilateral rales, and bilateral pitting edema. Labs showed mildly low HB of 11.7, low Na of 125 mmol/L, elevated creatinine at 1.67 mg/dl, low urine osmolality at 270 mOsm/kg, and BNP of 24 with negative troponin. Chest x-ray showed cardiomegaly. TSH was elevated at 93 uIU/mL and low free T4 at less than 0.25 ng/dL with a negative anti-TPO. A diagnosis of amiodarone-induced hypothyroidism was made, and the patient was started on increased furosemide and levothyroxine 25 mcg daily. Significant improvement was noted in mental status, sodium level, and volume status within three days; and the patient was discharged home on 50mcg of levothyroxine. Discussion: This case illustrates the need to constantly investigate the etiology of decompensated heart failure, especially when new medications with potential culprit side effects are noted or suspected. Amiodarone which is helpful in the management of atrial fibrillation has been known to cause thyroid dysfunction as hypo or hyperthyroidism. What is not widely known is that these endocrine dysfunctions can occur just a few weeks after therapy initiation. Conclusion: We recommend that patients who started on amiodarone be monitored for thyroid dysfunction; especially when they present with deterioration in the cardiac function or show symptoms of endocrinopathy.

Transient Bradyarrhythmia

Amiodarone is a class III anti-arrhythmic drug which is commonly used in various cardiac arrhythmias. Hypothyroidism is one important complication linked with this drug. Herein, we recount a case of amiodarone-induced hypothyroidism, which presented as atrial fibrillation (AF) with slow ventricular response. A middle-aged gentleman was brought to the casualty in unconscious state. He was a known case of hypertension and on amiodarone treatment for AF for the past 2 years. On presentation, the patient had a slow pulse rate and his electrocardiogram was suggestive of AF with very slow ventricular beat. This was managed medically and a temporary cardiac pacemaker was instituted thereafter. In search of the cause for bradycardia, his thyroid function test depicted hypothyroidism with 2-fold raised thyroid-stimulating hormone and decreased levels of free tetraiodothyronine hormone, but the patient had no other features suggestive of hypothyroidism. Therefore, the patient was started on oral thyroxine hormone, which led to considerable pulse rate improvement.

Draft of the federal clinical recommendations for diagnosisi and treatment of amiodarone-induced thyroid dysfunction

Amiodarone is an antiarrhythmic drug that is commonly used for treatment of various supraventricular and ventricular arrhythmias. Amiodarone and its main active metabolite desethylamiodarone have a direct dose-dependent cytotoxic effect on thyroid follicular cells. Consequently, some patients receiving amiodarone may develop thyroid dysfunction: amiodarone-induced hypothyroidism (AIH) or amiodarone-induced thyrotoxicosis (AIT). The diagnosis, classification, and treatment of amiodarone-induced thyroid dysfunction remain to be a challenge to all clinicians deal with this problem. This draft of clinical recommendations was developed by a group of specialists experienced in the diagnosis and treatment of amiodarone-induced thyroid dysfunction. AIH does not require amiodarone withdrawal. Thyroxine treatment is recommended for all patients with manifest AIH, subclinical forms of AIH do not always need its prescription. There are two main types of amiodarone-induced thyrotoxicosis: AIT type 1 (is a hyperthyroidism that develops due to excessive iodine intake in autonomous thyroid nodules or latent Graves ‘ disease) and AIT type 2 (develops due to destructive thyroiditis because of the cytotoxic effect of amiodarone). In addition, there is a mixed form, which has features of both types of AIT. Autonomous AIT 1 is characterized by the presence of one or more «hot» nodules in the thyroid. Elevated TSH receptor antibodies or typical clinical manifestations confirm the diagnosis of diffuse toxic goiter and, consequently, AIT1. Colour-flow Doppler sonography (CFDS) is proposed as the basic method of differential diagnosis of AIT 1 and AIT 2. CFDS «pattern 0», usually indicates AIT 2, the presence of «patterns I-III» mostly typical for AIT 1. The thyreostatics are recommended for AIT 1, oral glucocorticoids for AIT 2 and their combination for a mixed AIT. Emergency thyroidectomy should be applied to patients with deteriorating cardiovascular pathology and ineffective drug therapy. In the absence of clinical suspicion on thyroid dysfunction, thyroid hormones assessment should be done 3 months after the start of amiodarone treatment, thereafter every 6 months.

Polypharmacy Is Associated With Amiodarone-Induced Hypothyroidism.

Background: Amiodarone is rich in iodine, so in clinical practice amiodarone-induced hypothyroidism (AIH) is a major side effect. This drug is used in patients with arrhythmias, especially atrial fibrillation, the most common sustained arrhythmia. Polypharmacy, which can result in complex drug-drug interactions, occurs in more than 70% of the patients with atrial fibrillation. Therefore, polypharmacy may be involved in the expression of AIH. In this study, we investigated the association between polypharmacy and AIH.Methods: We conducted a retrospective study using data from January 2006 to May 2020 collected from a large, organized database of prescriptions constructed by the Japan Medical Information Research Institute, Inc. (Tokyo, Japan). To investigate the association between number of prescribed drugs with amiodarone and AIH, we divided patients into two groups: polypharmacy (≥ 5 prescribed drugs) and non-polypharmacy (< 5 prescribed drugs). We then performed a sequence symmetry analysis on the two groups: incident thyroxine after incident amiodarone and incident thyroxine before incident amiodarone. Finally, we conducted a case-control study on two further groups: those prescribed thyroxine after incident amiodarone (AIH group; n=555) and those not prescribed thyroxine after incident amiodarone (non-AIH group; n=6,192).Results: Sequence symmetry analysis revealed a significant association between amiodarone and thyroxine in both the polypharmacy and non-polypharmacy groups. The ranges for the adjusted sequence ratio in the two groups were 12.0-16.7 and 7.3-9.0, respectively. The case-control study showed that ≥5 prescribed drugs at the first prescription of amiodarone were found to significantly increase the odds of AIH (odds ratio: 1.48, 95% confidence interval: 1.18-1.84).Conclusion: Polypharmacy was suggested as an independent risk factor for AIH. Careful assessment of the appropriateness of prescription is warranted.

Amiodarone-induced thyroid dysfunction in children: insights from the THYRAMIO study.

Background:Amiodarone treatment is effective against various types of arrhythmias but is associated with adverse effects affecting, among other organs, thyroid function. Amiodarone-induced thyroid dysfunction was not thoroughly evaluated in children as it was in adults, yet this affection may lead to irreversible neurodevelopmental complications. Our study aimed to define the incidence and risk factors of amiodarone-induced thyroid dysfunction in children.Methods:The study was designed as an observational study with a retrospective clinical series of 152 children treated by amiodarone in the Pediatric Cardiology Unit of our center from 1990 to 2019. All patients were divided into three groups according to their thyroid status: euthyroid, AIH (amiodarone-induced hypothyroidism) or AIT (amiodarone-induced thyrotoxicosis). Patients from these three groups were compared in terms of key clinical and therapeutic features.Results:Amiodarone-induced thyroid dysfunction was present in 23% of patients. AIT (5.3%) was three times less common than AIH (17.7%), and its occurrence increased with older age (p < 0.05), treatment dosage (p < 0.05), treatment duration (p < 0.05) and the number of loading doses administered (p < 0.05). There were no distinctive clinical features between euthyroid and AIH groups. A multivariable prediction model of AIT was built, with a yield of 66.7% as positive predictive value and 96.7% as negative predictive value.Conclusion:We observed that one in five children developed amiodarone-induced thyroid dysfunction. Special attention is required for older children with a high dosage and long-term therapy and who received a large number of loading doses, since these children are at risk to develop AIT, which is more delicate to manage than AIH.

The effects of amiodarone on thyroid function in pediatric and young adult patients

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.

Amiodarone-Induced Hypothyroidism

Aim: to present a clinical case of amiodarone-induced hypothyroidism in a patient with paroxysmal atrial fi brillation.Results. Before taking amiodarone, the patient suffered from subclinical hypothyroidism. The level of thyroid stimulating hormone (TSH) was 6.2 mIU/L, thyroxine (T4) — 9.2 pmol/L. Against the background of taking amiodarone in a maintenance dose of 200 mg per day 5 days a week with a break of 2 days, clinically severe hypothyroidism developed with a TSH level of more than 16 mIU/L. An electrocardiogram (ECG) recorded sinus bradycardia with a heart rate (HR) of 37 beats per minute. Paroxysms of atrial fi brillation have stopped. According to the daily ECG monitoring recorded throughout the sinus rhythm with maximum heart rate of 92 beats/min., minimum of 35 beats/min. The circadian rhythm profi le was correct. No pauses were detected for more than two seconds. Transient atrioventricular block was of 1 degree (during sleep). Ectopic activity was represented by supraventricular extrasystoles 112 per day: 107 single, 1 pair, 1 group. Ventricular extrasystoles: 55 per day: polymorphic, solitary. No diagnostically signifi cant elevation or depression of the ST segment was detected. After the abolition of amiodarone, thyroid function was recovered. Levothyroxine was not prescribed. However, paroxysms of atrial fi brillation began to occur again. For the prevention of paroxysms, sotalol 160 mg per day was prescribed.Conclusion. Thus, the development of clinically pronounced amiodarone-induced hypothyroidism has contributed to the existing thyroid dysfunction in the patient. The assessment of the thyroid gland function and its further monitoring in the process of taking the drug is prescribed. Amiodarone therapy is performed in case of ineffectiveness of other antiarrhythmic drugs and, as a rule, is not used for primary prescription.

Amiodarone-induced thyroid dysfunction in the developmental period: prenatally, in childhood, and adolescence - case reports and a review of the literature.

Amiodarone is an important antiarrhythmic drug used in paediatric practice, mainly in children with complex congenital cardiac diseases and/or severe arrhythmias. One of the side effects of amiodarone therapy is thyroid dysfunction, which is observed in about 20% of patients. The thyroid dysfunction may present with various forms: from subclinical changes in hormone levels to amiodaroneinduced thyrotoxicosis (AIT) and amiodarone-induced hypothyroidism (AIH). We reported six patients in the age range from two weeks to 14 years, with complex congenital cardiac diseases and severe arrhythmias, who developed amiodarone-induced thyroid dysfunctions: thyrotoxicosis or hypothyroidism or both together. The clinical signs and symptoms of all thyroid dysfunctions were atypical, most patients presented with an aggravation of heart insufficiency. Our patients with thyrotoxicosis were treated with combined therapy including thionamides and corticosteroids due to the presentation of mixed-identified type of AIT. Currently, five patients (one patient's status is unknown) are in biochemical and clinical euthyreosis; however, in one of them it was impossible to discharge amiodarone treatment. Three of them are still treated with levothyroxine, and two do not need thyroid treatment. Amiodarone-induced thyroid dysfunction is usually atypical; therefore, monitoring of thyroid status before, during, and after amiodarone is demanded. AIH could significantly influence the development of the child, while AIT could significantly deteriorate the clinical status of children with complex cardiac diseases. Early and proper diagnose of AIT and AIH allows the introduction of immediate and appropriate treatment considering the cardiac condition of the young patient.

The Effects of Amiodarone on Thyroid Function in Pediatric and Young Adult Patients

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. 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. Retrospective review of thyroid dysfunction in children and young adults treated with amiodarone between 2007 and 2018. Children's Hospital of Philadelphia. Children and young adults treated with amiodarone. Prevalence of amiodarone-induced thyroid dysfunction. 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. 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.