Hyperthyroidism.

Thyrotoxicosis causes a variety of symptoms and adverse health outcomes. Hyperthyroidism refers to increased thyroid hormone synthesis and secretion, most commonly from Graves' disease or toxic nodular goitre, whereas thyroiditis (typically autoimmune, viral, or drug induced) causes thyrotoxicosis without hyperthyroidism. The diagnosis is based on suppressed serum concentrations of thyroid-stimulating hormone (TSH), accompanied by free thyroxine and total or free tri-iodothyronine concentrations, which are raised (overt hyperthyroidism) or within range (subclinical hyperthyroidism). The underlying cause is determined by clinical assessment, detection of TSH-receptor antibodies and, if necessary, radionuclide thyroid scintigraphy. Treatment options for hyperthyroidism include antithyroid drugs, radioactive iodine, and thyroidectomy, whereas thyroiditis is managed symptomatically or with glucocorticoid therapy. In Graves' disease, first-line treatment is a 12-18-month course of antithyroid drugs, whereas for goitre, radioactive iodine or surgery are preferred for toxic nodules or goitres. Evidence also supports long-term treatment with antithyroid drugs as an option for patients with Graves' disease and toxic nodular goitre.

Hyperthyroidism: A Review.

Importance: Overt hyperthyroidism, defined as suppressed thyrotropin (previously thyroid-stimulating hormone) and high concentration of triiodothyronine (T3) and/or free thyroxine (FT4), affects approximately 0.2% to 1.4% of people worldwide. Subclinical hyperthyroidism, defined as low concentrations of thyrotropin and normal concentrations of T3 and FT4, affects approximately 0.7% to 1.4% of people worldwide. Untreated hyperthyroidism can cause cardiac arrhythmias, heart failure, osteoporosis, and adverse pregnancy outcomes. It may lead to unintentional weight loss and is associated with increased mortality. Observations: The most common cause of hyperthyroidism is Graves disease, with a global prevalence of 2% in women and 0.5% in men. Other causes of hyperthyroidism and thyrotoxicosis include toxic nodules and the thyrotoxic phase of thyroiditis. Common symptoms of thyrotoxicosis include anxiety, insomnia, palpitations, unintentional weight loss, diarrhea, and heat intolerance. Patients with Graves disease may have a diffusely enlarged thyroid gland, stare, or exophthalmos on examination. Patients with toxic nodules (ie, in which thyroid nodules develop autonomous function) may have symptoms from local compression of structures in the neck by the thyroid gland, such as dysphagia, orthopnea, or voice changes. Etiology can typically be established based on clinical presentation, thyroid function tests, and thyrotropin-receptor antibody status. Thyroid scintigraphy is recommended if thyroid nodules are present or the etiology is unclear. Thyrotoxicosis from thyroiditis may be observed if symptomatic or treated with supportive care. Treatment options for overt hyperthyroidism from autonomous thyroid nodules or Graves disease include antithyroid drugs, radioactive iodine ablation, and surgery. Treatment for subclinical hyperthyroidism is recommended for patients at highest risk of osteoporosis and cardiovascular disease, such as those older than 65 years or with persistent serum thyrotropin level less than 0.1 mIU/L. Conclusions and Relevance: Hyperthyroidism affects 2.5% of adults worldwide and is associated with osteoporosis, heart disease, and increased mortality. First-line treatments are antithyroid drugs, thyroid surgery, and radioactive iodine treatment. Treatment choices should be individualized and patient centered.

[Radioactive iodine in the treatment of Graves' disease: history and modern concept of radionuclide therapy].

Radioactive iodine 131I is a theranostic isotope used both for diagnosis and therapy of benign thyroid diseases and thyroid cancer for 85 years. The formation of nuclear medicine is closely linked with the use of 131I. The history of radioiodine therapy began in 1941, when endocrinologist Saul Hertz for the first time used 131I to treat patients with Graves' disease. Since 1946 radioactive iodine 131I became widely available, and its effectiveness became public knowledge after reports on thyrotoxicosis treatment published in the Journal of the American Medical Association by multidisciplinary groups of scientists - physicists and endocrinologists. In 1951, isotope 131I became the first Food and Drug Administration approved RP for the treatment of thyroid disorders. Around the same time on the basis of the First Moscow Medical Institute studies on the use of radioiodine isotopes in patients with thyrotoxicosis began. The head of the Soviet group on the studying of radioactive iodine was the physician-scientist Vera Georgievna Spesivtseva. The research works of medical physicists Edith Quimby and Leonidas Marinelli in optimizing therapeutic strategies using radioactive substances in the late 1940s and the wording of the ALARA (As Low As Reasonably Achievable) principle of minimizing exposure of ionizing radiation by the International Commission on Radiological Protection in 1954 contributed to the greater introduction of radionuclides into the medicine.

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.

Thyrotoxicosis and dilated cardiomyopathy in developing countries.

BACKGROUND: Thyrotoxicosis is the state of thyroid hormone excess. But, in sub-Saharan Africa (SSA), specifically Northern Ethiopia, scientific evidence about thyrotoxicosis and its cardiac complications like dilated cardiomyopathy is limited. Therefore, this study aimed to explore the thyrotoxicosis presentation and management and identify factors associated with dilated cardiomyopathy in a tertiary hospital in Northern Ethiopia. METHODS: An institution-based cross-sectional study was conducted in Ayder Comprehensive Specialized Hospital from 2017 to 2018. Data from 200 thyrotoxicosis cases were collected using a structured questionnaire. After describing variables, logistic regression was conducted to identify independent predictors of dilated cardiomyopathy. Statistical significance was declared at p < 0.05. RESULTS: Mean age at presentation of thyrotoxicosis was 45 years and females accounted for 89 % of the cases. The most frequent etiology was multinodular toxic goiter (51.5 %). As well, the most common symptoms and signs were palpitation and goiter respectively. Thyroid storm occurred in 6 % of the cases. Out of 89 patients subjected to echocardiography, 35 (39.3 %) of them had dilated cardiomyopathy. And, the odds of dilated cardiomyopathy were higher in patients who had atrial fibrillation (AOR = 15.95, 95 % CI:5.89-38.16, p = 0.001) and tachycardia (AOR = 2.73, 95 % CI:1.04-7.15, p = 0.040). All patients took propylthiouracil and 13.0 % of them experienced its side effects. Concerning ß-blockers, propranolol was the most commonly (78.5 % of the cases) used drug followed by atenolol (15.0 %). Six patients underwent surgery. CONCLUSIONS: In developing countries like Ethiopia, patients with thyrotoxicosis have no access to methimazole which is the first-line anti-thyroid drug. Besides, they greatly suffer from dilated cardiomyopathy (due to late presentation) and side effects of propylthiouracil. Therefore, we recommend that patients should get adequate health information about thyrotoxicosis and anti-thyroid drugs including their side effects. Additionally, hospitals and other concerned bodies should also avail of TSH tests and methimazole at an affordable cost. Furthermore, community awareness about iodized salt and iodine-rich foods should be enhanced.

Therapeutic plasma exchange with albumin as a valuable method of preparing thyrotoxic patients for a life-saving thyroidectomy.

Hyperthyroidism affects approximately 1.2% of the population and its routine treatment includes antithyroid drugs (ATDs), radioiodine and surgery. Management of patients with resistance or contraindications to ATDs who require thyroidectomy may be challenging. We present the experience of our department in preparing thyrotoxic patients for life-saving thyroidectomy by using therapeutic plasma exchange (TPE) with albumin: one patient with Graves' disease and previous history of agranulocytosis and cholestatic jaundice after ATDs and two patients with amiodarone-induced thyrotoxicosis. Five to six TPEs were applied to each patient resulting in a decrease of fT3 by 57% to 83%, fT4 by 21% to 60% and decrease/normalization of total thyroid hormones. All patients underwent surgery successfully. In case of drug-resistant thyrotoxicosis or contraindications to ATDs, TPE can be a valuable tool in preparing patients for surgery. Albumin used as a replacement fluid appears to be effective in ameliorating clinical and laboratory symptoms of thyrotoxicosis.

Therapeutic plasmapheresis for the treatment of thyrotoxicosis: A retrospective multi-center study.

BACKGROUND AND AIMS: Thyroid storm and severe thyrotoxicosis remain among the most frequent endocrine emergencies, and first-line hyperthyroidism treatment is not always an option. Since the first report in 1970, plasmapheresis is a second-line treatment for severe or otherwise untreatable thyrotoxicosis when rapid euthyroidism is desired. METHODS: We present a retrospective study of the experience in treating thyrotoxicosis with plasmapheresis between 2012 and 2020 in two specialized centers in Colombia. We register the demographic and clinical characteristic and compare the thyroid hormones and other biochemical measurements before and after treatment. RESULTS: Data from 19 patients was obtained, 58% female with a median age of 35 years (IQR 23.5), and most of them with Graves' disease. The most frequent indication for plasmapheresis was thyroid storm. A median of 4 (IQR 2) sessions lead to a significant reduction in FT4 (P .0001) and TT3 (P < .0003) with a nonsignificant decrease in beta-blocker (P .7353) dose, no change in hepatic enzymes, and no adverse events. After plasmapheresis, thyroidectomy was performed in 10 patients. CONCLUSIONS: Plasmapheresis is an effective and safe treatment option for reducing circulating thyroid hormones in severe thyrotoxicosis when other forms of treatment are contraindicated or in case of urgent thyroid and non-thyroid surgery. It is limited by its cost and the need for highly specialized resources.

Hyperthyroidism.

Thyrotoxicosis is a general term for excess circulating and tissue thyroid hormone levels, whereas hyperthyroidism specifically denotes disorders involving a hyperactive thyroid gland (Graves disease, toxic multinodular goiter, toxic adenoma). Diagnosis and determination of the cause rely on clinical evaluation, laboratory tests, and imaging studies. Hyperthyroidism is treated with antithyroid drugs, radioactive iodine ablation, or thyroidectomy. Other types of thyrotoxicosis are monitored and treated with ß-blockers to control symptoms given that most of these conditions resolve spontaneously.

Syndrome of thyrotoxicosis. Differential diagnosis and treatment.

Since the middle of the twentieth century, there has been a significant change in methods of the diagnosis and treatment of thyroid diseases with thyrotoxicosis syndrome. Previously doctors did not have trouble just with diagnosing diseases that occur with a typical clinical presentation (the Merzeburg triad, a multinodal goiter with fibrillation) because of no possible to determine thyroid hormones. Then in the early 70s years the appearance of immunological methods for estimating hormones in the blood has led to significant changes in our understanding of the variants of thyroid pathology with thyrotoxicosis (TT). Today, the diagnosis of the fact of thyrotoxicosis as a whole is not difficult (except for the confusion of preanalytical errors), but differential diagnosis within the declared syndrome remains extremely relevant to this day. Unfortunately, in the minds of many doctors, these diseases are sometimes perceived as a whole, and in the conditions of the "century of speeds", a modern doctor, extremely limited in time, often unjustifiably prescribes thyreostatic therapy, treatment with radioactive iodine or even surgical intervention after detecting thyrotoxicosis. The old truth "remember that a patient with thyrotoxicosis is a person with a sick heart..." has not lost relevance today. It is very important for the practicing physician be able to navigate in the spectrum of pathologies manifested by the thyrotoxicosis pattern because of the influence of excess thyroid hormones on the cardiovascular system and the hemostasis system. Hereinafter we tried to show diagnostic aspects focusing on differences in pathologies with TT syndrome in a lot of thyroid diseases and even nonthyroid diseases.

Managing thyrotoxicosis in the acute medical setting.

Thyrotoxicosis is common and can present in numerous ways with patients exhibiting a myriad of symptoms and signs. It affects around 1 in 2000 people annually in Europe1. The thyroid gland produces two thyroid hormones - thyroxine (T4) and triiodothyronine (T3). Thyroxine is inactive and is converted by the tissues and organs that need it into tri-iodothyronine. In health, the production of these thyroid hormones is tightly regulated by the secretion of thyroid stimulating hormone (TSH; thyrotropin) from the pituitary gland. The term 'thyrotoxicosis' refers to the clinical manifestations of hyperthyroidism.

Iatrogenic thyrotoxicosis and the role of therapeutic plasma exchange.

Thyroid storm or severe thyrotoxicosis results from extreme thyroid hormone elevation. Therapy includes medical management to prevent hormone production, release, recycling, and peripheral conversion while stabilizing adrenergic tone. Thyroid dysfunction is the usual cause but it can be due to excessive thyroid hormone ingestion. Therapeutic plasma exchange (TPE) has been used to rapidly remove protein-bound thyroid hormone. American Society for Apheresis guidelines make a weak recommendation to perform TPE in selected patients in the treatment of thyrotoxicosis based on low quality evidence. We present a case of excessive thyroid replacement hormone ingestion treated by TPE. The patient presented with the clinical picture of thyroid storm, including cardiovascular compromise and massively elevated total and free T3 (525 ng/dL, nl 80-200 ng/dL and 28 pg/mL, nl 2.0-3.5 11 pg/mL), which failed medical therapy. A single, one plasma volume TPE was performed. Both total and free T3 demonstrated substantial declines immediately after TPE with the patient's mental status returning to near-normal. Thyroid hormone extraction efficiency and collection efficacy were calculated as 37.1% and 40.8%, respectively. Prior to discharge on day 6, the patient's compounding pharmacy indicated that a "bad batch" of bovine thyroid gland derived replacement hormone had been produced. TPE appears to be effective in removing protein bound thyroid hormone in extreme iatrogenic thyrotoxicosis.

[Clinical features of patients with Basedow Graves disease seen at a university hospital]. / Caracterización de pacientes controlados por enfermedad de Basedow Graves en un hospital universitario.

BACKGROUND: Basedow Graves disease (BGD) is the leading cause of hyperthyroidism. The characteristics of patients seen at a university hospital may differ from those described in the general population. AIM: To describe the clinical features of patients with BGD seen at a university hospital. MATERIAL AND METHODS: Review of medical records of all patients seen at our hospital between 2009 and 2014 with the diagnosis of thyrotoxicosis, hyperthyroidism or BGD. Clinical features, laboratory results and treatments were recorded. RESULTS: We reviewed clinical records of 272 patients; 15 had to be excluded due to incomplete data. BGD was present in 77.9% (n = 212). The mean age of the latter was 42 years (range 10-81) and 76% were women. Ninety six percent were hyperthyroid at diagnosis and thyroid stimulating hormone was below 0.1 mIU/L in all patients. Median free thyroxin and triiodothyronine levels were 3.26 ng/dl and 3.16 ng/ml, respectively. Thyrotropin-receptor antibodies were positive in 98.5% and 85.7% had positive thyroid peroxidase antibodies. Graves orbitopathy (GO) was clinically present in 55% of patients. Of this group, 47% had an active GO, 26% had a moderate to severe disease and 7.8% had sight-threatening GO. As treatment, 26% received radioiodine, 44% anti-thyroid drugs exclusively, 28% underwent thyroidectomy and 2% did not require therapy. CONCLUSIONS: In this group of patients, we observed a greater frequency of severe eye disease and a high rate of surgical management. This finding could be explained by referral to highly qualified surgical and ophthalmological teams.

[What's new in the 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis].

The 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis has been officially published in October of 2016, five years after the publication of the previous version. Revised contents in the new guideline are summarized in this review.

2016 Guidelines for the management of thyroid storm from The Japan Thyroid Association and Japan Endocrine Society (First edition).

Thyroid storm is an endocrine emergency which is characterized by multiple organ failure due to severe thyrotoxicosis, often associated with triggering illnesses. Early suspicion, prompt diagnosis and intensive treatment will improve survival in thyroid storm patients. Because of its rarity and high mortality, prospective intervention studies for the treatment of thyroid storm are difficult to carry out. We, the Japan Thyroid Association and Japan Endocrine Society taskforce committee, previously developed new diagnostic criteria and conducted nationwide surveys for thyroid storm in Japan. Detailed analyses of clinical data from 356 patients revealed that the mortality in Japan was still high (∼11%) and that multiple organ failure and acute heart failure were common causes of death. In addition, multimodal treatment with antithyroid drugs, inorganic iodide, corticosteroids and beta-adrenergic antagonists has been suggested to improve mortality of these patients. Based on the evidence obtained by nationwide surveys and additional literature searches, we herein established clinical guidelines for the management of thyroid storm. The present guideline includes 15 recommendations for the treatment of thyrotoxicosis and organ failure in the central nervous system, cardiovascular system, and hepato-gastrointestinal tract, admission criteria for the intensive care unit, and prognostic evaluation. We also proposed preventive approaches to thyroid storm, roles of definitive therapy, and future prospective trial plans for the treatment of thyroid storm. We hope that this guideline will be useful for many physicians all over the world as well as in Japan in the management of thyroid storm and the improvement of its outcome.

[Rarer causes of thyrotoxicosis]. / Rzadsze przyczyny nadczynnosci tarczycy.

Thyrotoxicosis is a pathological syndrome in which tissue is exposed to excessive amounts of circulating thyroid hormones. Including its subclinical form, it is considered as one of the most frequent endocrine disorders in the general population. If not detected in a timely fashion, thyrotoxicosis can have serious health consequences. The most common forms of thyrotoxicosis include diffuse toxic goiter (Graves' disease), toxic multinodular goiter (Plummer's disease), and toxic adenoma (Goetsch's disease). The significant progress in the fields of hormonal assessment, imaging procedures and molecular biology made in recent years has brought about great improvement in the identification, differentiation and treatment of many other disorders associated with thyrotoxicosis. Therefore, this paper discusses the etiopathogenesis, clinical manifestation, biochemical abnormalities and management of thyrotropinoma, resistance to thyroid hormone, de Quervain's, silent, acute, posttraumatic and radiation-induced thyroiditis, Riedel's goiter, differentiated thyroid cancer, struma ovarii, thyrotoxicosis factitia, other forms of iatrogenic thyrotoxicosis, gestational trophoblastic disease, neonatal Graves's disease, familial nonautoimmune hyperthyroidism and McCune-Albright syndrome. On the basis of available studies, some of whom were carried out in the recent years, we provide practical guidelines for clinical endocrinologists dealing with the diagnosis and treatment of thyrotoxicosis.

Therapeutic Plasmapheresis Enabling Radioactive Iodine Treatment in a Patient with Thyrotoxicosis.

Therapeutic plasma exchange (TPE) is one possible treatment for patients resistant to conventional antithyroid drugs or requiring urgent attention for thyrotoxicosis. We report a 35-yr-old man with thyrotoxicosis, ultimately attributed to Graves' disease in whom antithyroid drug used initially was soon discontinued, due to abnormal liver function, and replaced by Lugol's solution. Three weeks later, an escape phenomenon (to Lugol's solution) was apparent, so we performed TPE to control the thyrotoxicosis. Two courses of TPE by a centrifugal type machine resulted in diminished levels of thyroid hormone levels, which then rebounded after another two courses of membrane filtration type TPE. However, the patient could be treated with radioactive iodine therapy without any complications at present.

Preoperative therapeutic apheresis for severe medically refractory amiodarone-induced thyrotoxicosis: a case report.

INTRODUCTION: Amiodarone is associated with thyroid dysfunction and life-threatening thyrotoxicosis. In medically refractory cases, or where medical therapy is contraindicated, thyroidectomy may be required. To decrease perioperative thyroid storm and to reduce overall surgical risk, apheresis may be considered preoperatively to restore euthyroidism. CASE DESCRIPTION: We report a 46-year-old female with a history of cardiac arrhythmia and tachycardia-induced cardiomyopathy for which she received amiodarone. Months after discontinuation of amiodarone, the patient presented with wide complex tachycardia and symptoms of thyrotoxicosis. Laboratory testing confirmed severe thyrotoxicosis which was subsequently refractory to medical therapy. Total thyroidectomy was required. Following a total of 10 apheresis treatments, thyroid hormone levels were reduced to near normal levels and the patient's symptoms improved. Thyroidectomy was performed without intraoperative or postoperative complication. DISCUSSION: In the setting of life-threatening, medically refractory amiodarone-induced thyrotoxicosis, therapeutic apheresis can effectively reduce thyroid hormone levels and restore a state of clinical and biochemical euthyroidism.

An audit of amiodarone-induced thyrotoxicosis--do anti-thyroid drugs alone provide adequate treatment?

INTRODUCTION: Amiodarone is a widely used anti-arrhythmic drug. A common long-term complication is amiodarone-induced thyrotoxicosis (AIT). We examined retrospectively the efficacy of anti-thyroid drugs with or without prednisolone and the role of surgical thyroidectomy in the treatment of AIT in a single centre, in an iodine-replete region of Australia. METHODS: A retrospective audit of patients with AIT was performed between 2002-2012 at this centre. Twenty-seven patients, mean age 60.9 ± 2.3 years were identified. Medical therapy (anti-thyroid drugs, prednisolone) was commenced according to the treating endocrinologist. The main outcomes were time to euthyroidism and number proceeding to thyroidectomy. RESULTS: Of 11 patients commenced on anti-thyroid drugs alone, seven (64%) required the addition of prednisolone. Baseline free T4 was significantly higher in those ultimately treated with prednisolone (58.4 ± 6.3pmol/L) versus those not (31.7 ± 3.4pmol/L, P<0.05). Although similar results were seen with free T3, the difference was not significant (P=0.06). In patients with baseline free T4 <30pmol/L, 75% (3/4) achieved euthyroidism without prednisolone. Neither the use of prednisolone nor continuation of amiodarone significantly influenced time to euthyroidism. Eleven patients (41%) proceeded to surgical thyroidectomy, which was undertaken by an experienced surgical team without significant complications and no mortality. CONCLUSION: Patients with AIT generally required glucocorticoids. Mild disease (free T4 <30pmol/L) may be successfully treated with anti-thyroid drugs alone. Surgical thyroidectomy is a safe and effective treatment for those refractive to medical therapy.