Thyroid Hormone Excess Research Articles

Extreme Weight Loss and Psychosis as Presenting Signs of Thyrotoxicosis

Thyroid storm is an acute, life-threatening syndrome due to an exacerbation of thyrotoxicosis, which is when you have an excess of thyroid hormone in the body. Thyroid storm can be precipitated by infections, surgery, or untreated thyrotoxicosis. Multisystem involvement is often seen. Typical symptoms include fever and tachycardia, which are rather common, as well as more severe symptoms such as atrial fibrillation, congestive heart failure, hepatic failure, delirium and coma. The Burch-Wartofsky Point Scale is often used for the clinical diagnosis of thyroid storm. Prompt diagnosis and therapy are required to prevent complications and mortality in patients with thyroid storm. Here we present a case of thyroid storm in a patient that presented with psychosis and significant weight loss.

The role of oxidative stress in the pathogenesis of Graves’ orbitopathy

Graves' disease (GD) is a chronic autoimmune condition, in which the anti-thyroid stimulating hormone receptor antibodies (TRAb) activate the thyrotropin receptor (TSHR) located on thyrocytes, leading to excessive thyroid hormone production. TSHR is also expressed in extrathyroidal tissues, in particular, within the orbit. The serum levels of TRAb corelate with severity and activity of thyroid orbitopathy (TO). TO is the most common extrathyroidal manifestation of GD. It is an autoimmune inflammation of orbital tissues, that is, extraocular muscles, orbital adipose tissue or a lacrimal gland. Increased orbital fibroblast and adipocyte proliferation, overproduction of glycosaminoglycans, as well as extraocular muscle oedema result in an increased orbital tissue volume and trigger the onset of TO symptoms. The pathophysiology of TO is complex and has not been fully unexplained to date. Orbital fibroblasts show expression of the TSHR, which is the main target of autoimmunity. It has been hypothesised that T-cell activation induced by orbital receptor stimulation by the target antibody results in orbital tissue infiltration, triggering a cascade of events which leads to the production of cytokines, growth factors and reactive oxygen species (ROS). ROS cause damage to many components of the cell: the cell membrane through the peroxidation of lipids and proteins leading to a loss of their function and enzymatic activity. Oxidative stress leads to activation of the antioxidant system which operates through two mechanisms: enzymatic and non-enzymatic. Assessment of the concentration of oxidative stress markers and the concentration or activity of antioxidative system parameters enables evaluation of oxidative stress severity, which in the future may be utilized for assessment of treatment efficacy and prognosis in patients with active OT.

The role of cardiovascular assessment in low risk thyroid neoplasm patients: results from a tertiary care center experience

<p class="abstract"><strong>Background:</strong> After surgery, clinical approach to thyroid neoplasms often involves TSH suppression. An increased cardiovascular (CV) risk due to thyroid hormones excess has already been proved. Aim of the study was to evaluate the role of CV assessment in preventing new events and optimizing the follow-up of these patients.</p><p class="abstract"><strong>Methods:</strong> After thyroidectomy for low risk thyroid neoplasms, a cohort of 108 women was retrospectively evaluated. A first examination (V1) at the end of primary treatments and a second one (V2) five years later were considered. Clinical and echocardiographic evaluations were performed in each examination. Patients were divided into 3 subclasses depending on TSH-suppression degree in the study period. New cardiovascular events, initiation of new therapies and cardiovascular deaths were recorded. </p><p class="abstract"><strong>Results:</strong> The incidence of CV events was 7,4%. Patients age (p=0.032), previous CV events (p=0.001), use of lipid-lowering (p=0.002) and antiplatelet (p=0.027) drugs and diabetes mellitus (p=0,049) were associated with total CV events; interventricular septum thickness, BMI and tryglicerides value with ischaemic events (sensitivity 66,6%, 100%, 80%; specificity 91,1%, 55,1%, 77,2%, respectively; p<0.001); TSH-suppression class with arrhythmic events (p=0.035); an increased left ventricular mass index ratio between V2 and V1 with both total (p=0.001) and ischaemic (p=0.002) CV events.</p><p class="abstract"><strong>Conclusions:</strong> After primary treatments for thyroid neoplasm, a complete CV assessment is advisable in defining TSH-suppression target. Ultrasound parameters appear useful in evaluating CV risk both at baseline and during the follow-up. A periodic revaluation of those parameters may allow the prevention or early diagnosis of new events and complications.</p>

When a storm showers the blood clots: a case of thyroid storm with systemic thromboembolism.

SummaryThyroid storm is a rare but potentially life-threatening complication of excessive thyroid hormone action. It is associated with a hypercoagulable state and reported to increase the risk of thromboembolism. However, the role of anticoagulation in thyroid storm still remains controversial and inconclusive. A 22-year-old male with no significant past medical history presented with acute severe generalised abdominal pain. He was found to be profoundly thyrotoxic on arrival at our institution and subsequently diagnosed with thyroid storm secondary to newly diagnosed Graves’ disease. Extensive thromboses of the splanchnic, iliac, femoral veins and pulmonary arteries were subsequently demonstrated on CT scan. He had prolonged bowel ileus as a sequela of mesenteric ischaemia requiring total parenteral nutrition and non-oral forms of anti-thyroid drugs for management of hyperthyroidism. He was in sinus rhythm throughout his inpatient stay, and there was no personal history of prothrombotic conditions. His thrombophilia screen was normal. He eventually required jejunectomy due to jejunal ischaemia from extensive involvement of portal and mesenteric veins. He underwent radioiodine ablation for definitive treatment. He is currently hypothyroid and receiving thyroxine replacement. Thyroid storms are hypercoagulable states and can be associated with extensive thromboembolism even in the absence of atrial fibrillation. To our knowledge, this is the first report of severe extensive thromboembolism complicated by severe mesenteric ischaemia and bowel ileus in the setting of a thyroid storm. Routine prophylactic anticoagulation should be considered in those presenting with thyroid storms.Learning pointsProlonged use of rectal propylthiouracil (PTU) for managing hyperthyroidism was effective in a patient who cannot take oral anti-thyroid drugs.Hyperthyroidism is a hypercoagulable state due to an imbalance between coagulation and fibrinolytic factors.Thyroid storm can be associated with extensive thromboembolism even in the absence of atrial fibrillation; routine prophylactic anticoagulation should be considered in the setting of thyroid storms.

TSH secreting pituitary tumor — an experience of 20 years follow-up

Thyrotropinoma is a rare pituitary tumor that causes the development of thyrotoxicosis syndrome as a result of hyperproduction of thyroid stimulating hormone (TSH). In the Russian literature over the past 10 years, one case of thyrotropinoma in a child, four cases of TSH-producing pituitary adenoma in women and only one in a man have been described. The article presents a unique clinical case of a 20-years history of observation of a patient with TSH-oma. The rarity of this disease led to the fact that it took more than 10 years to make a correct diagnosis. The first operation of thyroid gland was performed before the diagnosis of pituitary adenoma and inappropriate TSH secretion syndrome. That right hemithyroidectomy was supposed to cure a toxic adenoma of thyroid gland. The diagnosis of thyrotropin-secreting piruitary tumor was established only after 6 years even after finding a combination of pituitary adenoma and thyrotoxicosis. After that, the patient steadfastly refuses neurosurgical treatment, despite the presence of macroadenoma with intrasellar growth. The therapy with somatostatin analogs led to patient’s intolerance with gastrointestinal side effects and hospitalization for acute pancreatitis. The absence of the therapy due to low compliance led to long-term persistence of thyrotoxicosis. The absence of signs and symptoms of expanding tumor mass (visual field defects, loss of vision, headache, partial or total hypopituitarism) demonstrates the slow growth of this kind of pituitary tumor. The long-term effect of elevated TSH levels led to diffuse goiter with compression of the neck organs, and the need of the surgical treatment of the thyroid. Stable euthyroidism after the operation led to stable normoglycemia in the patient with previously diagnosed diabetes mellitus type 2. This fact should keep an attention of physicians and endocrinologists to screen for the secondary reasons of hyperglycemia in a patient with diabetes mellitus manifestation. Long-term history of thyrotoxicosis led to the deleterious effects of thyroid hormone excess on the heart (atrial fibrillation, cardiomyopathy, cardiac failure). Those effects are still observed even after thyroidectomy and medical euthyroidism achievement. This fact demonstrates the importance of early diagnosis and treatment of TSH-omas.

Rola stresu oksydacyjnego w patogenezie orbitopatii Gravesa

Streszczenie Choroba Gravesa-Basedowa (chGB) jest przewlekłą chorobą autoimmunologiczną, której auto-antygenem jest receptor TSH (TSHR) umiejscowiony na tyreocytach, a jego pobudzenie przez przeciwciała przeciwko TSHR (TRAb) powoduje nadmierne wytwarzanie hormonów tarczycy. TSHR wykazuje także ekspresję w tkankach pozatarczycowych, przede wszystkim w tkankach oczodołu, a stężenie TRAb w surowicy krwi dodatnio koreluje z ciężkością oraz aktywnością orbitopatii tarczycowej (OT). OT jest najczęstszym pozatarczycowym objawem chGB. Jest to choroba autoimmunologiczna, w której dochodzi do zmian zapalnych w obrębie tkanek oczodołów, tj.: mięśniach okoruchowych, tkance tłuszczowej oczodołu czy gruczole łzowym. Wzrost proliferacji fibroblastów oczodołowych i adipocytów oraz nadmierne wytwarzanie glikozaminoglikanów, obrzęk mięśni okoruchowych zwiększają objętość tkanek oczodołu i powodują powstanie objawów klinicznych choroby. Patogeneza OT jest złożona i nadal pozostaje niewyjaśniona. Fibroblasty oczodołów wykazują ekspresję TSHR, który jest głównym miejscem ataku autoimmunologicznego. Zgodnie z szeroko akceptowaną hipotezą po pobudzeniu receptorów dochodzi do aktywacji limfocytów T, które naciekając tkanki oczodołu stymulują je do wytwarzania cytokin, czynników wzrostu oraz wolnych rodników tlenowych (WRT). WRT powodują uszkodzenie wielu składowych komórki m.in. błony komórkowej przez peroksydację lipidów oraz białek doprowadzając do utraty ich funkcji i aktywności enzymatycznej. Stres oksydacyjny uaktywnia układ antyoksydacyjny działający poprzez dwa mechanizmy: enzymatyczny oraz nieenzymatyczny. Ocena stężenia markerów stresu oksydacyjnego oraz stężenia lub aktywności parametrów układu antyoksydacyjnego umożliwia ocenę nasilenia stresu oksydacyjnego, co w przyszłości może być wykorzystywane do oceny skuteczności leczenia i rokowania u chorych z aktywną OT.

HYPERTHYROIDISM: LOOKING BEYOND PHYSICIAN'S PERSPECTIVE

Hyperthyroidism with its excess circulatory thyroid hormones commonly presents with systemic features like palpitation, weight loss and heat intolerance. This hyperadrenergic, hypermetabolic state with its peripheral and central nervous system affection produces protean neurological manifestations which are generally overlooked by internist. Features of neuropsychiatric nature, cognitive impairment, and dementia movement disorder like tremors or chorea may be presentation of undetected hyperthyroidism. Affliction for muscles presents with proximal myopathy with or without myalgia in 50-70% of long standing hyperthyroid state. Similarly thyrotoxic periodic paralysis due to low serum potassium in adult male is often misdiagnosed as Guillain-Barré syndrome, however replacement of potassium drastically reverse the condition. There is a strong association between autoimmune thyroiditis and ocular myesthenia which post difficulties in clinical diagnosis. Despite of so much variability in clinical presentation attainment of euthyroid state coupled with beta blocker in many situations is helpful to resolve most of the issues. Keywords: Hyperthyroidism, Grave's, Tremors, Myopathy, Periodic paralysis.

A clinical comparative study & efficacy of polyherbal Unani formulations in subclinical hypothyroidism & overt hypothyroidism (Qillat-E-Ifraz-E-Ghudde Darqiyya)

The thyroid gland is a small organ that’s located in front of the neck, wrapped around the windpipe (trachea). The thyroid secretes two essential hormones T3 - Triiodothyronine & T4 – Thyroxine, collectively called thyroid hormones. Their secretion is under the control of TSH from Pituitary and TRH from Hypothalamus. During infancy and childhood, adequate thyroid hormone is crucial for brain development. The prevalence of hypothyroidism in developed countries is around 4-5%, whereas it is about 11% in India. It is more common in women than in men. Hypothyroidism has multiple etiologies and manifestations. The most common clinical manifestations are weight gain, loss of hair, cold intolerance, lethargy, constipation, dry skin, and change in voice. The signs and symptoms of hypothyroidism differ with age, gender, severity of condition, and some other factors. The diagnosis is based on clinical history, physical examination and serum level of FT3, FT4, and TSH (Thyroid-stimulating hormone), imaging studies, procedures, and histological findings. The description of hypothyroidism as a disease is not directly found in Unani texts. However, the signs and symptoms of hypothyroidism resemble the clinical manifestation associated with Su-e-Mizaj Barid Maddi (derangement in cold temperment). These observations from Unani literature describe derangement in cold temperament and relate them to the clinical presentation of primary hypothyroidism in conventional medicine. Increasing dosage and continuous medicine make the patient drug dependent till the end of the life. Even after years of treatment, it is associated with failure to provide relief in clinical manifestations. Moreover, excessive thyroid hormone replacement carries the potential for serious long‑term metabolic complications (e.g.,accelerated osteoporosis). In the USM, the main emphasis of the principle of treatment (Usool-e-Ilaj) is to correct the abnormal constitution (Su-e-Mizaj) and alter the six prerequisites for existence (Asbab-e-Sitta Zarooriya) to restore normal health. It is a packaged treatment, that is, different components of treatment are given as a package form which includes correction in diet, different drugs, dosages form, and regimens. Due to certain limitation and associated side effects, this conventional medicine has certain limitations, which can be overcome by using unani herbal formulations either in single form or compound form. This unani medicine can limit the subclinical hypothyroidism at its level and prevent it from moving to overt hypothyroidism. The present Research study on “Efficacy of Unani Herbs in Treating Subclinical & Overt Hypothyroidism” was conducted on 10 patients from either gender whose TSH value was above normal (> 4.5ng/dl). They were divided in two groups of 5 patients each and was treated with separate group of medicine A & B. They were under observation for nearly 2 months. It was elicited that this disease effects the female most and of cold temperment. This research study ultimately concluded that Group A medicine has better response than Group B medicine with a 60% Cured, 20% Partial response & 20% No response. Group B also showed response but with efficacy lesser than Group A.

A NOT SO SIMPLE THYROID CAUSE OF ST DEPRESSION: THYROTOXIC HYPOKALEMIC PERIODIC PARALYSIS

SESSION TITLE: Medical Student/Resident Cardiovascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Thyrotoxic hypokalemic periodic paralysis (THPP) is a rare and reversible endocrine emergency. The excess of thyroid hormone increases the sensitivity of the Na-K-ATPase channels, shifting potassium from the extracellular to the intracellular space. CASE PRESENTATION: A previously healthy 53 year-old man presented with one day of generalized weakness. Associated symptoms included lower extremities paresthesias, headaches, nausea and vomiting in addition to 5 months of fatigue, weight loss and tremors. Physical findings were significant for a heart rate of 117bpm and a blood pressure of 140/65mmHg. Extremities were warm, clammy and well perfused. A fine hand tremor, diffuse weakness and hypotonia were present. EKG showed sinus tachycardia, diffuse ST depression and QT interval prolongation (figure 01). Laboratory showed a critical hypokalemia (at 1.63mEq/L), a suppressed TSH (<0.005µIU/mL) and an elevated T4L (4,03ng/dL). Intravenous potassium chloride was administered. EKG after KCl infusion (Figure 02) showed resolution of the repolarization changes. His muscular weakness also resolved. Patient was discharged with propranolol and methimazole for outpatient follow up. DISCUSSION: THPP is more common in men in between the age of twenty to forty Hypokalemia results in slowed conduction, delayed ventricular repolarization, shortened refractory period and increased automaticity. ECG changes include flattening and inversion of T waves in mild hypokalemia, Q-T interval prolongation and mild ST depression in more severe hypokalemia. Severe hypokalemia can cause torsades de pointes and ventricular tachycardia. Importantly ST depression as in our case is not common and should raise the concern for ischemia if not resolved with potassium reposition. CONCLUSIONS: THPP is a rare cause of hypokalemia which can cause malignant arrythmias. Severe hypokalemia is an unusual cause of ST segment depression, ventricular tachycardia and QT prolongation, being an important differential for ischemic heart disease. Reference #1: Lin YC, Wu CW, Chen HC, Chen HY, Lu IC, Tsai CJ, Kuo WR, Chiang FY. Surgical treatment for thyrotoxic hypokalemic periodic paralysis: case report. World jorunal of surgical oncology. 2012;10(1):21. Reference #2: Osadchii OE. Mechanisms of hypokalemia-induced ventricular arrhythmogenicity. Fundam Clin Pharmacol. 2010; 24:547–59. DISCLOSURES: No relevant relationships by RAIMUNDO BARROS, source=Web Response no disclosure on file for Lucia Belem; No relevant relationships by Ingrid Freitas, source=Web Response No relevant relationships by Simran Kenth, source=Web Response No relevant relationships by Neiberg de Alcantara Lima, source=Web Response No relevant relationships by Danielli Lino, source=Web Response No relevant relationships by José Silva, source=Web Response

Тиреотропинома — опыт 20-летнего наблюдения

Thyrotropinoma is a rare pituitary tumor that causes the development of thyrotoxicosis syndrome as a result of hyperproduction of thyroid stimulating hormone (TSH). In the Russian literature over the past 10 years, one case of thyrotropinoma in a child, four cases of TSH-producing pituitary adenoma in women and only one in a man have been described. The article presents a unique clinical case of a 20-years history of observation of a patient with TSH-oma. The rarity of this disease led to the fact that it took more than 10 years to make a correct diagnosis. The first operation of thyroid gland was performed before the diagnosis of pituitary adenoma and inappropriate TSH secretion syndrome. That right hemithyroidectomy was supposed to cure a toxic adenoma of thyroid gland. The diagnosis of thyrotropin-secreting piruitary tumor was established only after 6 years even after finding a combination of pituitary adenoma and thyrotoxicosis. After that, the patient steadfastly refuses neurosurgical treatment, despite the presence of macroadenoma with intrasellar growth. The therapy with somatostatin analogs led to patient’s intolerance with gastrointestinal side effects and hospitalization for acute pancreatitis. The absence of the therapy due to low compliance led to long-term persistence of thyrotoxicosis. The absence of signs and symptoms of expanding tumor mass (visual field defects, loss of vision, headache, partial or total hypopituitarism) demonstrates the slow growth of this kind of pituitary tumor. The long-term effect of elevated TSH levels led to diffuse goiter with compression of the neck organs, and the need of the surgical treatment of the thyroid. Stable euthyroidism after the operation led to stable normoglycemia in the patient with previously diagnosed diabetes mellitus type 2. This fact should keep an attention of physicians and endocrinologists to screen for the secondary reasons of hyperglycemia in a patient with diabetes mellitus manifestation. Long-term history of thyrotoxicosis led to the deleterious effects of thyroid hormone excess on the heart (atrial fibrillation, cardiomyopathy, cardiac failure). Those effects are still observed even after thyroidectomy and medical euthyroidism achievement. This fact demonstrates the importance of early diagnosis and treatment of TSH-omas.

New Therapeutic Horizons for Graves' Hyperthyroidism.

Graves’ hyperthyroidism is characterized by the presence of autoantibodies that stimulate the thyroid-stimulating hormone receptor (TSHR), resulting in uncontrolled secretion of excessive thyroid hormone. Conventional treatments, including antithyroid medication, radioiodine, or surgery have remained largely unchanged for the past 70 years and either lack efficacy for many patients, or result in lifelong thyroid hormone replacement therapy, in the case of the latter 2 options. The demand for new therapeutic options, combined with greater insight into basic immunobiology, has led to the emergence of novel approaches to treat Graves’ hyperthyroidism. The current therapies under investigation include biologics, small molecules, and peptide immunomodulation. There is a growing focus on TSHR-specific treatment modalities, which carry the advantage of eliciting a specific, targeted approach, with the aim of avoiding disruption of the functioning immune system. These therapies present a new opportunity to supersede the inadequate treatments currently available for some Graves’ patients, offering hope of successful restoration of euthyroidism without the need for ongoing therapy. Several of these therapeutic options have the potential to translate into clinical practice in the near future. This review provides a comprehensive summary of the recent advances and various stages of development of the novel therapeutic approaches to treat Graves’ hyperthyroidism.

Immunological Drivers in Graves' Disease: NK Cells as a Master Switcher.

Graves' disease (GD) is a common autoimmune cause of hyperthyroidism, which is eventually related to the generation of IgG antibodies stimulating the thyrotropin receptor. Clinical manifestations of the disease reflect hyperstimulation of the gland, causing thyrocyte hyperplasia (goiter) and excessive thyroid hormone synthesis (hyperthyroidism). The above clinical manifestations are preceded by still partially unraveled pathogenic actions governed by the induction of aberrant phenotype/functions of immune cells. In this review article we investigated the potential contribution of natural killer (NK) cells, based on literature analysis, to discuss the bidirectional interplay with thyroid hormones (TH) in GD progression. We analyzed cellular and molecular NK-cell associated mechanisms potentially impacting on GD, in a view of identification of the main NK-cell subset with highest immunoregulatory role.

Graves' disease.

Graves' disease (GD) is an autoimmune disease that primarily affects the thyroid gland. It is the most common cause of hyperthyroidism and occurs at all ages but especially in women of reproductive age. Graves' hyperthyroidism is caused by autoantibodies to the thyroid-stimulating hormone receptor (TSHR) that act as agonists and induce excessive thyroid hormone secretion, releasing the thyroid gland from pituitary control. TSHR autoantibodies also underlie Graves' orbitopathy (GO) and pretibial myxoedema. Additionally, the pathophysiology of GO (and likely pretibial myxoedema) involves the synergism of insulin-like growth factor 1 receptor (IGF1R) with TSHR autoantibodies, causing retro-orbital tissue expansion and inflammation. Although the aetiology of GD remains unknown, evidence indicates a strong genetic component combined with random potential environmental insults in an immunologically susceptible individual. The treatment of GD has not changed substantially for many years and remains a choice between antithyroid drugs, radioiodine or surgery. However, antithyroid drug use can cause drug-induced embryopathy in pregnancy, radioiodine therapy can exacerbate GO and surgery can result in hypoparathyroidism or laryngeal nerve damage. Therefore, future studies should focus on improved drug management, and a number of important advances are on the horizon.

Urgent surgery in a poorly controlled hyperthyroid patient

Hyperthyroidism is a multisystemic disease with its main effects on the cardiovascular system. It is better to control thyroid hormone excess before surgery to avoid the risk of precipitating thyroid storm. This won’t be practical in emergency or urgent surgeries. This is a case history of a 50 year old man with uncontrolled hyperthyroidism who underwent a gastrectomy for a carcinoma. Hyperthyroidism was managed with antithyroid drugs, beta blockers, glucocorticoids and magnesium sulphate.

Tirotoxicosis e hipertiroidismo

Thyrotoxicosis is a clinical disorder caused by an caused by the effect of excess of thyroid hormone in tissues, whereas hyperthyroidism refers to an increased thyroid hormone synthesis and secretion. Diagnosis is achieved by the measurement of the serum TSH and thyroid hormones (thyroxine and triiodothyronine). Etiology has to be identified in order to set up a proper treatment. Graves-Basedow disease (an autoimmune thyroid disorder) is the commonest cause of hyperthyroidism, followed by toxic nodular goiter or toxic thyroid adenoma (autonomous secreting thyroid nodules). In the thyroiditis, the thyroid gland is inflamed and the thyroid hormones are released. In the estruma ovarii the thyroid hormones have an extrathyroidal origen whereas in thyrotoxicosis facticia the origin of such an excess is exogenous. Etiological diagnosis of thyrotoxicosis and hyperthyroidism is based on clinical examination, laboratory and imaging (ultrasonography and scintigraphy) tests. The treatment of hyperthyroidism depends on the etiology and is focused in treating the symptoms as well as in reduce the synthesis and secretion of thyroid hormones (pharmacological treatment, radioiodine therapy and surgery).

Disruption of BMP Signaling Prevents Hyperthyroidism-Induced Bone Loss in Male Mice.

Thyroid hormones (TH) are key regulators of bone health, and TH excess in mice causes high bone turnover-mediated bone loss. However, the underlying molecular mechanisms of TH actions on bone remain poorly defined. Here, we tested the hypothesis whether TH mediate their effects via the pro-osteogenic bone morphogenetic protein (BMP) signaling pathway in vitro and in vivo. Primary murine osteoblasts treated with 3,3',5-triiodo-L-thyronine (T3 ) showed an enhanced differentiation potential, which was associated with activated canonical BMP/SMAD signaling reflected by SMAD1/5/8 phosphorylation. Blocking BMP signaling at the receptor (LDN193189) and ligand level (noggin, anti-BMP2/BMP4 neutralizing antibodies) inhibited T3 -induced osteogenic differentiation. In vivo, TH excess over 4 weeks in male C57BL/6JRj mice led to severe trabecular bone loss with a high bone turnover that was completely prevented by treatment with the BMP ligand scavenger ALK3-Fc. Thus, TH activate the canonical BMP pathway in osteoblasts to promote their differentiation and function. Importantly, this study indicates that blocking the BMP pathway may be an effective strategy to treat hyperthyroidism-induced bone loss. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

SAT-498 Graves’-Associated Takotsubo Cardiomyopathy: An Uncommon Condition

Introduction Graves’ disease is an autoimmune disorder that causes excess thyroid hormone (T4 and T3). T4 is converted into T3 (active hormone) in the peripheral tissues by the deiodinase enzyme. T3 has an effect on the cardiac electrical system as well as myocyte contractility. Excess T3 can result in cardiac arrythmias as well as ventricular dysfunction (heart failure). Takotsubo cardiomyopathy is a subtype of nonischemic cardiomyopathy related to severe physiologic or mental stress. Excess catecholamine levels have been reported to cause this disease as well. Takotsubo cardiomyopathy has rarely been reported in Graves’-associated thyrotoxicosis. Case report 55-year-old female who presented to the ED with palpitations and difficulty breathing. She had been seen by her PCP within the past two weeks with complaint of recent 30 lb weight. TSH was noted to be < 0.001 and a neck ultrasound revealed a diffusely enlarged, hypervascular thyroid. She was referred for outpatient endocrinology consultation for further workup. Prior to her initial endocrinology appointment, she developed palpitations and shortness of breath. She did not have any known family history of thyroid disease or other autoimmune conditions. She drinks 1-2 glasses of wine per week and quit smoking in 2017. Physical exam on admission revealed a heart rate of 133 bpm and a blood pressure of 145/93, normal temperature, and normal respirations. Thyroid was diffusely enlarged and without nodularity. No evidence of orbitopathy. Heart was tachycardic but without murmur. Lungs clear. Abdomen soft, nontender. No significant peripheral edema or pretibial rash. No neurological dysfunction. Labs revealed TSH < 0.001, Free T4 > 7.77, Free T3 12.0, TRAb 44.4%, TSI 433%, Anti-TPO 614, high-sensitivity troponin of 112. EKG showed nonspecific infero-lateral T wave changes, rate 123. Echocardiogram demonstrated left ventricular apical hypokinesis but preserved basilar contractility. Ejection fraction was estimated at 40-45%. Nuclear stress test did not reveal any indication of myocardial hypoperfusion. Discussion/Conclusion Takotsubo cardiomyopathy can mimic acute myocardial infarction both clinically as well as on EKG/serum biomarkers. Troponin levels are typically elevated as a result of myocardial stretch and subsequent troponin “leak”. Echocardiogram demonstrates apical ballooning of the left ventricle, and by definition coronary arteries will be free of significant occlusive disease. A small number of cases have been reported in association with endocrine conditions including thyrotoxicosis due to Graves’ disease. The majority of cases associated with thyrotoxicosis will resolve spontaneously with 1-3 weeks. Treatment consists of medication to decrease cardiac preload as well as afterload (ACE inhibitor, beta blocker, diuresis as needed), similar to medical treatment of other nonischemic cardiomyopathies.

SAT-075 Pulmonary Hypertension in a Patient with Neonatal Graves Disease

INTRODUCTIONNeonatal hyperthyroidism is a transient disorder seen in neonates born to mothers with current or past history of Graves’ disease. We present a rare case of a Neonatal Graves’ disease with pulmonary hypertension (PH) which completely resolved with treatment of hyperthyroidism.CLINICAL CASEBaby B was a 3200 g term male born to a 40-year-old hypothyroid mother. He was prenatally diagnosed with Trisomy 21 and coarctation of the aorta (CoA). He developed respiratory distress soon after birth and was admitted to the NICU. His echocardiogram (echo) showed a large patent ductus arteriosus (PDA) and increased tortuosity of juxtaductal aorta with no significant gradient. Near-systemic pulmonary artery pressure was noted in the absence of any evidence of left heart failure. Cardiology determined his CoA to be hemodynamically insignificant and not the cause of his PH. Successive trials of 100% FiO2, Nitric Oxide (NO), and Sildenafil resulted in only minimal improvement of his PH.Thyroid function tests (TFT) obtained on day of life (DOL) 8 showed serum TSH of 0.01 uIU/ml [0.87 - 6.43] and FT4 of 3.5 ng/dl [0.9 - 1.5]. Further interaction with the mother revealed that she had a history of Graves’ disease treated with radioactive iodine (RAI) and resultant hypothyroidism. Baby B’s TSH receptor antibody (TRAb) and thyroid stimulating immunoglobulin levels were elevated at 7.38 IU/l [0-1.75] and 3.38 IU/l [0-0.55], respectively.He was thus diagnosed with Neonatal Graves’ disease and was started on Methimazole (MTZ) 1 mg/kg/day on DOL 8. Subsequently, potassium iodide was added. FT4 showed gradual normalization by DOL 15. Beta blockers were not added due to absence of hypertension or significant tachycardia. Serial echo showed improvement of PH, consistent with the decline in FT4 levels. Sildenafil and FiO2 were slowly weaned and discontinued by DOL 30. MTZ was then tapered and discontinued. A final echo showed complete resolution of PH, unobstructed aortic arch and persistent PDA.DISCUSSIONNeonatal hyperthyroidism occurs due to transplacental transfer of TRAb from mother to fetus, stimulating the fetal thyroid to make excessive thyroid hormones. Risk correlates with TRAb titers in the mother. Our patient had pulmonary hypertension which did not resolve with FiO2, NO and Sildenafil. However, it showed complete resolution with normalization of FT4 levels by antithyroid drugs. Hyperthyroidism commonly presents with systemic HTN, but we found 3 neonatal cases in the literature presenting with PH that resolved with treatment of hyperthyroidism. The mechanism is unclear, but hypotheses include increased clearance of pulmonary vasodilators and decreased clearance of pulmonary vasoconstrictor and decreased surfactant production/function(1).REFERENCES1) Oden J, Cheifetz IM. Neonatal thyrotoxicosis and persistent PH necessitating extracorporeal life support. Pediatrics 2005-115: e105-8.

SAT-462 Coronary Vasospasm-Induced Myocardial Infarction: An Uncommon Presentation of Thyrotoxicosis

Background: Coronary artery vasospasm-induced myocardial infarction is a rare cardiac complication of untreated thyrotoxicosis. Diagnosis is difficult due to the transient and unpredictable occurrence of coronary spasm [1]. Clinical Case: A 47-year-old Hispanic female smoker presented with a one-week history of severe, intermittent substernal chest pain radiating to the left arm. The pain was associated with palpitations and shortness of breath. She was afebrile with a heart rate of 100, a blood pressure of 119/59, a fine tremor, and brisk reflexes. No lid lag or proptosis was appreciated. The thyroid was enlarged, non-tender, without palpable nodules. ECG showed T- Wave Inversions in leads V1-V2 and ST depressions in V4-V5. Chest pain was relieved by SL nitroglycerin.Lab results showed a peak Troponin of 0.20 (N < 0.06), TSH 0.01 mU/L (N > 0.45mU/L), free T4 5.54 (N < 1.46 ng/dl), total T3 4.50 pg/mL (N < 1.37 ng/mL), free T3 21.0 ng/mL (N < 4.4 pg/ml), TSI 3.61 IU/L (N < 0.55 IU/L), thyrotropin R Ab 7.47 IU/L (N < 1.75 IU/L) and thyroglobulin Ab 1.3 IU/ml (ULN < 0.9 IU/ml). Thyroid US showed a heterogeneous enlarged thyroid gland with increased vascularity.For her NSTEMI she was treated with a heparin drip, aspirin, clopidogrel, atorvastatin, propranolol, and isosorbide mononitrate. Methimazole was started to treat thyrotoxicosis. Cardiac catheterization revealed coronary vasospasm without evidence of valvular or coronary artery disease. Methimazole restored euthyroidism and she has not had recurrence of angina. Discussion: Rarely, hyperthyroidism can present with transient myocardial ischemia secondary to coronary artery vasospasm in patients with normal coronary arteries. The etiopathogenesis is unclear and may relate to a direct metabolic effect of excess thyroid hormone on the myocardium. In a Korean study evaluating chest pain in patients who underwent coronary angiography, the incidence of coronary vasospasm was 5%, occurring most frequently in women under 50 years of age with thyrotoxicosis [2]. Conclusion: Patients who present with angina and are thyrotoxic should be evaluated for vasospasm. Females under 50 years old with Graves’ disease are at highest risk. Treatment includes antithyroid medications along with nitroglycerin, and we can consider calcium channel blockers including diltiazem. Treatment of thyrotoxicosis eliminates recurrence of vasospasm [3].

SUN-515 Use of Plasmapheresis for Treatment of Thyroid Storm Resistant to Antithyroidals

Management strategies of thyroid storm include measures to reduce thyroid hormone synthesis, hormone release, conversion from T4 to T3, and inhibition of the peripheral effects of excessive thyroid hormone. Plasmapheresis has been described as a treatment option when traditional therapy is not successful or not feasible.We present a case of an adult patient who presented in thyroid storm in whom plasmapheresis was used successfully as a bridge to thyroidectomy.51-year-old female with history of hypertension presented with sudden onset shortness of breath, and palpitations. She had an irregular heart rate of 140BPM, respiratory rate of 40, mean arterial blood pressure 65mmHg. Electrocardiogram confirmed atrial fibrillation with rapid ventricular response and the patient was admitted to the intensive care unit. She was started on diltiazem drip and subsequently received amiodarone and electrical cardioversion due to persistent rapid heart rate. She developed respiratory distress and required endotracheal intubation.Initial thyroid profile revealed low TSH and normal FreeT4, but her FT4 increased above normal on day 2, treatment for thyroid storm was initiated with potassium iodine, hydrocortisone and propylthiouracil. She was kept on propranolol 80 mg q/4h, intravenous esmolol 50 mcg/kg/min, diltiazem drip 5 mg/hr, and was started on Digoxin 0.25 mg q/4h. TSI and TPO were undetectable, and thyroid ultrasound revealed a right nodule measuring 5 x 2.2 x 3.7cm. Thyroid storm was attributed to a toxic nodule exacerbated by exposure to excess iodine (contrast for imaging and amiodarone). Propylthiouracil, hydrocortisone and beta blocker were maximized, and cholestyramine was added, but their heart rate remained elevated, blood pressure worsened requiring synchronized cardioversion.Because of persistent hyperthyroid state, refractory to medical treatment, patient was started on plasmapheresis on day 10 of hospitalization, she underwent 5 sessions with significant reduction in Free T3 and Free T4 (Figure 1), and remarkable improvement in her hemodynamic status and resolution of tachycardia. Patient underwent total thyroidectomy on day 16, without complications.Plasmapheresis has been described as a treatment option for refractory thyroid storm, as a bridge therapy prior thyroidectomy. During plasmapheresis, thyroid-binding globulin, thyroid hormones, cytokines and putative antibodies are removed with the plasma; then the colloid replacement provides new binding sites for circulating free thyroid hormone (2). Although albumin binds thyroid hormone less avidly than TBG, it provides a much larger capacity for low-affinity binding that may contribute to lower free thyroid hormone levels, providing a window for thyroidectomy.1.Muller C et al, Role of Plasma Exchange in the Thyroid Storm, Therapeutic Apheresis and Dialysis15 (6): 522–531