Monitoring thyroid function during amiodarone use.

Treatment with recombinant interferon-alpha (rIFN-alpha) may induce autoimmunity. We have evaluated the effect of rIFN-alpha on pre-existing thyroid disease with special reference to changes in TSH receptor antibody. Five patients, who had a history of autoimmune thyroid disease diagnosed between 2 and 16 years earlier (three patients had Graves' disease while two had Hashimoto's thyroiditis), were treated with rIFN-alpha for chronic hepatitis C. Before, during and after rIFN-alpha therapy, we determined thyroid function, antithyroid antibody, thyroid echogenicity and the surface phenotype of the peripheral and intrathyroidal lymphocytes. Four of the patients developed overt hypothyroidism after 4-7 months of rIFN-alpha therapy, and two of them had a preceding history of low-uptake thyrotoxicosis. Recovery of thyroid function was observed in all four patients. Strongly positive blocking type TSH receptor antibody was detected and an increase in the percentage of CD19 positive cells in the intrathyroidal lymphocytes was also observed in three of the patients even though the goitre size increased in two of them. One of the patients became thyrotoxic later when stimulating type TSH receptor antibody became positive. Another patient suffered from reversible hypothyroidism although stimulating type TSH receptor antibody remained strongly positive throughout the clinical course. Our data thus indicated a high incidence of an unusual type of reversible hypothyroidism with TSH receptor antibodies in patients with chronic hepatitis C and pre-existing autoimmune thyroid disease after recombinant interferon-alpha therapy through a mechanism involving both the humoral and cellular immune systems.

Study question What is the thyroid disease rate in IVF patients and how does it affect their IVF outcome? Summary answer The thyroid disease rate was 19,5%, mostly of inflammatory origin. IVF outcome in these patients was similar to controls, but coexisting endometriosis rate was higher. What is known already Thyroid disease is the most common endocrine disorder in females of reproductive age. It is estimated that 20% of infertile females has history of thyroid disease. Thyroid hormones importantly impact fertility, acting directly on oocytes, sperm and embryo during fertilization, implantation and placentation, regulating estrogen and androgen metabolism as well as the menstrual cycle. The most common causes of thyroid disfunction are autoimmune disorders. The prevalence of thyroid autoimmunity among women undergoing IVF treatment is higher compared to the general population. Women with thyroid autoimmunity have higher risk of miscarriage, preterm birth and it may impact the IVF-ET outcome. Study design, size, duration It was a single center trial at the Division of Obstetrics and Gynecology, Department of Human Reproduction in the University Medical Centre of Ljubljana, Slovenia. The study included women undergoing their first IVF treatment in a one-year period. Participants/materials, setting, methods A total of 226 women undergoing their first IVF treatment were included. In the first part of our study, Patient characteristics and IVF outcome according to different TSH serum levels (< 0,59 mE/L, 0,59 - 2,5 mE/L, 2,5 - 4,23 mE/L ter > 4,23 mE/L) were analysed. In the second part of the study, we compared patient characteristics and IVF outcome in patients with and without thyroid disease. Main results and the role of chance The average age was 33 ± 4,7 years, the average BMI was 24±4,9 kg/m2. Three percent of women had TSH levels <0,59 mE/L, 74% had TSH levels 0,59-2,5 mE/L,18% had TSH levels 2,5-4,23 mE/L and 6% had TSH levels >4,23 mE/L. The obesity rate (BMI>30 kg/m2) was significantly different in all four groups of patients with the highest rate in the group of TSH 2,5-4,23 mE/L. Thyroid disease was found in 19,5% of patients (thyroid autoimmunity 18%, Hashimoto's thyroiditis 7,5% of patients). The thyroid disease rate was significantly different in all four groups with highest rate in group having TSH >4,23 mE/L and the lowest rate in group having TSH 0,59-2,5 mE/L. Endometriosis was diagnosed in 22% of patients with highest rate in patients having highest TSH levels. There was no correlation between patient characteristics and reproductive history (age, irregular menstrual cycle, dysmenorrhea, pregnancy, spontaneous abortion, recurrent abortion, FSH and LH serum levels) and TSH levels or preexisting thyroid disease. There were no significant differences in the IVF outcome (numbers of retrieved oocytes, immature oocytes and number of embryos) according to TSH levels or preexisting thyroid disease. Thyroid disease rate was significantly higher in patients with endometriosis. Limitations, reasons for caution Our study limitation is a smaller sample size that may affect our results, specifically the differences in the IVF outcome. There was no statistical difference in miscarriage and recurrent miscarriage rate in women with thyroid disease and women with normal thyroid function. Wider implications of the findings Our study gives an insight to the characteristics of women with thyroid disease undergoing IVF treatment in our facility, although the differences were statistically insignificant. As a secondary outcome we discovered a statistically significant correlation of endometriosis and inflammatory thyroid disease, which is rarely mentioed in the literature. Trial registration number not applicable

Background: Little evidence is available about the risk of sudden sensorineural hearing loss (SSNHL) in patients with thyroid diseases. We assessed whether a diagnosis of thyroid disease, particularly hyperthyroidism or hypothyroidism, is associated with SSNHL risk in an Asian population. Material and Methods: This case-control study was conducted with population-based data from Taiwan’s National Health Insurance Research Database from January 2000 to December 2013. The case group comprised 3331 adult patients with newly diagnosed SSNHL, and four controls without SSNHL for each case matched by sex, age, monthly income, and urbanization level of residence. Underlying Thyroid diseases were retrospectively evaluated in the case and control groups. Multivariate logistic regression analyses were used to explore relations between thyroid diseases and SSNHL. Results: Of the 3331 cases, 5.7% had preexisting thyroid diseases, whereas only 4.0% of the 13,324 controls had the same condition. After adjustment for sex, age, monthly income, urbanization level of residence, history of hypertension, diabetes mellitus, chronic otitis media, and hyperlipidemia, associations were identified between a history of either hypothyroidism (adjusted odds ratio [AOR], 1.54; 95% CI, 1.02–2.32; p = 0.042) or hyperthyroidism (AOR, 1.41; 95% CI, 1.07–1.85; p = 0.015) and an elevated risk of SSNHL. In subgroup analysis, the correlation between hypothyroidism and increased SSNHL risk remained significant only for patients aged over 50 years (AOR, 1.61; 95% CI, 1.01–2.57; p = 0.045), and that between hyperthyroidism and SSNHL was significant only for female patients (AOR, 1.48; 95% CI, 1.09–2.01; p = 0.012). Treatment for hypothyroidism and hyperthyroidism did not alter the association in subgroup analyses. Conclusion: Preexisting hypothyroidism and hyperthyroidism appear associated with SSNHL susceptibility in Taiwan. Physicians should be wary of this elevated risk of SSNHL among patients with previously diagnosed thyroid dysfunction, especially women and patients aged more than 50 years.

Amiodarone is used increasingly in a number of cardiac conditions. Amiodarone is heavily iodinated and can cause thyroid dysfunction. The diagnosis of amiodarone-induced thyrotoxicosis remains difficult and more common causes of thyrotoxicosis need to be considered and excluded. Amiodarone has a significant side effect profile, which includes thyroid dysfunction. Amiodarone is an effective drug and its withdrawal may have significant impact on a patient's already fragile cardiac status. There are three different types of amiodarone-induced thyrotoxicosis (AIT) (I, II and mixed). Identification of the different subtypes of AIT allows a rational and appropriate management strategy to be chosen. Type I occurs in patients with underlying thyroid disease, whilst type II is thought to result from a destructive thyroiditis. Differentiation is based on clinical grounds together with investigations, which can include thyroid function test, radioiodine uptake scanning, measurement of interleukin-6 levels and colour flow Doppler sonography. Amiodarone should be discontinued in both types of AIT if the indication for its use is not a life-threatening cardiac condition. The management of type I centres around antithyroid drugs to control thyrotoxicosis and later consideration of more definitive treatment. Type II AIT responds to steroid therapy, although antithyroid drugs may be useful if symptoms are severe. Therapeutic options for refractory cases of AIT include surgery, radioiodine and plasmapheresis.

Amiodarone is a widely used antiarrhythmic drug, which contains 75 mg of iodide per 200 mg of active substance. Eight of our patients receiving long-term amiodarone therapy became hypothyroid. Seven of these patients had no previous history of thyroid dysfunction or goiter. Antithyroid antibodies were absent, and standard perchlorate discharge tests were positive in seven patients when hypothyroidism was diagnosed. In one patient, amiodarone therapy was withdrawn; over the next nine months, the hypothyroidism resolved, and results of the perchlorate discharge test reverted to normal. We conclude that amiodarone-induced hypothyroidism is similar to previously described iodide-induced hypothyroidism. It may develop in the absence of a previous history of thyroid disease, and all patients receiving long-term amiodarone therapy should therefore be regularly monitored for hypothyroidism.

Amiodarone-induced thyrotoxicosis (AIT) should be included in differential diagnoses of thyrotoxicosis in presence of a suggestive drug history. Adequate treatment requires knowledge of the underlying type of AIT. A 68-year-old male was admitted because of progressive dyspnea and tachyarrhythmia. Symptoms of thyrotoxicosis, including agitation, sleep disturbances, and palpitations, had developed 14 days earlier and the patient's condition had worsened despite initiation of antithyroid treatment. Laboratory values showed manifest hyperthyroidism. Thyroid autoantibodies proved negative. C-reactive protein and erythrocyte sedimentation rate were slightly increased. Ultrasound revealed a moderately increased thyroid without nodules and with normal perfusion. Suspecting AIT type 2, treatment with high-dosed glucocorticoids and antithyroid drugs was initiated. Under additional beta-blockade and heart insufficiency therapy the patient's condition significantly improved. After achievement of euthyreosis, thyroidectomy was performed. In patients with preexisting thyroid disorders, such as Grave's disease or functional autonomy in multinodular goiter, the high iodine content of amiodarone may cause iodine-induced thyrotoxicosis, also known as AIT type I. Treatment comprises high-dosed antithyroid drugs. In contrast, in patients suffering from AIT type II, toxic effects of amiodarone on a previously healthy thyroid result in destructive thyroiditis. Treatment consists of glucocorticoids in a dosage of 1 mg per kg body weight per day. Antithyroid treatment could be added in cases of equivocal diagnosis. In most cases, thyroidectomy is indicated. Whether amiodarone can be discontinued, should be discussed with the responsible cardiologist. Due to the long half-life time of amiodarone, treatment discontinuation will not result in an immediate improvement.

First-trimester care of maternal thyroid dysfunction has previously been shown to be poor. This study evaluates early management of thyroid dysfunction in pregnancy in Australia. Patients reviewed by the Obstetric Medicine team for thyroid dysfunction from 1 January 2012 to 30 June 2013 were included. Data were collected on gestation at referral from the patient's general practitioner to the antenatal clinic, information provided in the referral letter, thyroid function tests and thyroid medications. Eighty-five women were included in the study. At the time of general practitioner referral to antenatal services, 19% of women with preexisting thyroid disease had no thyroid function tested. Forty-three percent had an abnormal thyroid-stimulating hormone defined as being outside the laboratory-specific pregnancy reference range if available, or outside the level of 0.1-2.5 mIu/L in the first trimester, 0.2-3.0 mIu/L in the second trimester and 0.3-3.0 mIu/L in the third trimester. Only 21% of women increased their thyroxine dose prior to their first antenatal clinic review. This study highlights that a significant proportion of women with known thyroid disease either have untested thyroid function in the first trimester or a thyroid-stimulating hormone outside of levels recommended by guidelines.

Objective:The aim of this study was to evaluate thyroid dysfunction in COVID-19 and study its association with disease severity in COVID-19.Methods:Patients with confirmed COVID-19 infection who were admitted to dedicated COVID hospital were recruited over 3 months period. Those with pre-existing thyroid disease were excluded. The thyroid function tests were performed and correlated with interleukin-6 levels.Results:A total of 164 patients (14 children) with mean(SD) age 53.85 (19.54) years were recruited. The proportion of patients with mild, moderate and severe disease were 22 (13.4%), 78 (47.6%) and 64 (39.0%), respectively, among which 12 (54.5%), 56 (71.8%) and 43 (67.2%) patients had thyroid dysfunction, respectively; P = 0.309. Eighty eight (53.7%) had sick euthyroid (84 had low fT3 only), 14 had overt hypothyroidism and 9 had thyroiditis. Median (IQR) levels of serum fT3 showed significant decline from mild category [4.54 (3.81, 5.27)], to moderate [3.95 (3.67, 4.24)] and severe category [3.56 (3.22, 3.89)]; P = 0.011. Low fT3 had significant risk [odds ratio (95% CI)] of death [2.634 (1.01, 6.87); P = 0.031] and elevated IL-6 [2.575 (1.084, 6.118); P = 0.021].Conclusion:Sick euthyroid was seen in the majority of patients hospitalized with COVID. Low fT3 was associated with death and increased inflammation, suggesting poor prognosis.

To review management and dosing guidelines for amiodarone therapy, and discuss the drug's adverse event profile. Review of relevant studies and reports. Amiodarone is a highly effective antiarrhythmic drug, but is associated with adverse effects involving several organs. Amiodarone-induced arrhythmia is rare, with frequency of 0.3% in one study. Pulmonary toxicity is the most serious noncardiac side effect (2-17% of patients). Hypersensitivity pneumonitis can appear early in the course of therapy. Interstitial pneumonitis is a more common but insidious pulmonary reaction characterized by cough, low-grade fever, and dyspnea that occurs after months or years of therapy. Clinically important hypothyroidism and hyperthyroidism occur in 2-10% of patients. Optic neuritis or neuropathy in which patients experience decreased or blurred vision may progress to permanent blindness. Abnormalities in liver function tests, especially elevated aminotransferase and alkaline phosphatase levels, are seen in 4-25% of patients. Neurologic side effects were reported in 20-40% of patients, at times associated with tremor, ataxia, peripheral neuropathy, malaise or fatigue, sleep disturbances, dizziness, and headaches. Several types of dermatologic reactions have been reported, including allergic rash, photosensitivity, and blue-gray skin discoloration. The best strategy for early detection of pulmonary toxicity is vigilant clinical follow-up with monitoring of cardiac status and liver and thyroid function, and prescription of the lowest effective dosage. After an initial loading dose, 200 mg/day in many patients maintains arrhythmia control and minimizes the frequency of side effects. Amiodarone is a safe and efficacious antiarrhythmic agent when lower dosages are given to patients who are closely monitored and subject to careful follow-up.

Given the fact that a large number of radiological examinations using iodine-based contrast media (ICM) are performed in everyday practice, clinicians should be aware of potential ICM-induced thyroid dysfunction (TD). ICM can induce hyperthyroidism (Hyper) or hypothyroidism (Hypo) due to supraphysiological concentrations of iodine in the contrast solution. The prevalence of ICM-induced TD varies from 1 to 15%. ICM-induced Hyper is predominantly found in regions with iodine deficiency and in patients with underlying nodular goiter or latent Graves’ disease. Patients at risk for ICM-induced Hypo include those with autoimmune thyroiditis, living in areas with sufficient iodine supply. Most cases of ICM-induced TD are mild and transient. In the absence of prospective clinical trials on the management of ICM-induced TD, an individualized approach to prevention and treatment, based on patient’s age, clinical symptoms, pre-existing thyroid diseases, coexisting morbidities and iodine intake must be advised. Treatment of ICM-induced Hyper with antithyroid drugs (in selected cases in combination with sodium perchlorate) should be considered in patients with severe or prolonged hyperthyroid symptoms or in older patients with underlying heart disease. It is debated whether preventive therapy with methimazole and/or perchlorate prior to ICM administration is justified. In ICM-induced overt Hypo, temporary levothyroxine may be considered in younger patients with symptoms of Hypo, with an underlying autoimmune thyroiditis and in women planning pregnancy. Additional clinical trials with clinically relevant endpoints are warranted to further aid in clinical decision-making in patients with ICM-induced TD.

Traumatic hemorrhage of the thyroid gland is a rare injury with few published case reports. Surgical and nonsurgical management have been advocated but there is no consensus of opinion. This study is a retrospective review of published case reports including two own cases. A classification and an algorithm for diagnosis and treatment of thyroid gland injuries is proposed. A literature review reveals 16 case reports. Of these, 11 patients underwent neck exploration for control of hemorrhage and resection of the associated thyroid abnormality while 5 patients were conservatively managed. Of note is the fact that 10 of the 16 patients (63%) had pre-existing thyroid disease. These 10 patients constituted (91%) of the group requiring surgical treatment. Our proposed classification and algorithm offers management guidelines for this rather rare injury. Conservative treatment may be successful in selected patients with lower grade injuries and without concomitant thyroid disease.

Knowledge on the spectrum of thyroid disorders amongst Turner syndrome (TS) patients in Southeast Asia is limited. This study aimed to evaluate the prevalence of thyroid autoimmunity, the spectrum of autoimmune thyroid disease and association with age and karyotype amongst Malaysian TS girls. A cross-sectional study was conducted at 11 paediatric endocrine units in Malaysia. Blood samples for antithyroglobulin antibodies, antithyroid peroxidase antibodies and thyroid function test were obtained. In patients with pre-existing thyroid disease, information on clinical and biochemical thyroid status was obtained from medical records. Ninety-seven TS patients with a mean age of 13.4 ± 4.8 years were recruited. Thyroid autoimmunity was found in 43.8% of TS patients. Nineteen per cent of those with thyroid autoimmunity had autoimmune thyroid disease (Hashimoto thyroiditis in 7.3% and hyperthyroidism in 1% of total population). Patients with isochromosome X and patients with 45,X mosaicism or other X chromosomal abnormalities were more prone to have thyroid autoimmunity compared to those with 45,X karyotype (OR 5.09, 95% CI 1.54-16.88, P = 0.008 and OR 3.41, 95% CI 1.32-8.82, P = 0.01 respectively). The prevalence of thyroid autoimmunity increased with age (33.3% for age 0-9.9 years; 46.8% for age 10-19.9 years and 57.1% age for 20-29.9 years) with autoimmune thyroid disease detected in 14.3% during adulthood. Thyroid autoimmunity was significantly associated with the non 45,X karyotype group, particularly isochromosome X. Annual screening of thyroid function should be carried out upon diagnosis of TS until adulthood with more frequent monitoring recommended in the presence of thyroid autoimmunity.

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.

Background — Amiodarone-induced thyrotoxicosis (AIT) is a difficult management problem about which there are little published data. We examined whether continuing amiodarone or differentiating AIT into 2 subtypes affected outcome. Methods and Results — The type and duration of antithyroid treatment and response were recorded in a consecutive series of 28 cases. Comparisons were made between those in whom amiodarone either was continued or stopped and between those with either possible type 1 or type 2 AIT. Of the 28 cases, 5 had spontaneous resolution of AIT; 23 received carbimazole (CBZ) alone as first-line therapy. Eleven achieved long-term euthyroidism off CBZ or on a maintenance dose. Five became hypothyroid and required long-term thyroxine. Five relapsed after stopping CBZ treatment and were rendered euthyroid with either long-term CBZ (n=3) or radioiodine (n=2). Four were intolerant of CBZ and received propylthiouracil (PTU), with good effect in 3. One was resistant to thionamide alone (CBZ then PTU) and responded to adjunctive steroids. No difference in presentation or outcome was noted between those in whom amiodarone was continued or stopped or between possible type 1 or type 2 AIT. Conclusions — Continuing amiodarone has no adverse influence on response to treatment of AIT. First-line therapy with a thionamide alone is appropriate in iodine-replete areas, thus avoiding potential complications of other drugs. Differentiating between 2 possible types of AIT does not influence management or outcome.

Myxedema coma during long-term amiodarone therapy