Severe Hyperthyroidism Research Articles

SAT478 A Rare Case of Thyrotoxic Periodic Paralysis in a Patient with Concomitant Methimazole-Induced Agranulocytosis

Abstract Disclosure: K.S. Wei: None. S.M. Cannon: None. T.E. Angell: None. Introduction: Thyrotoxic state may precipitate sudden-onset unilateral or bilateral extremity weakness brought on by transient hypokalemia requiring specific management. Clinical Case: A 48-year-old woman presented to our hospital with fevers, sore throat, and sudden-onset bilateral leg weakness. Ten weeks prior, she was started on methimazole 20mg daily for a new diagnosis of Graves’ disease. Two days prior to presentation, she had consumed a carbohydrate-heavy meal and that night experienced acute-onset lower extremity weakness rendering her unable to walk. She also had been experiencing sore throat, odynophagia, and intermittent fevers. On admission, the patient was found to be febrile, tachycardic, and in shock with WBC <0.5 (ref: 4.5-10 K/cumm), potassium 2.6 (3.5-5.1 mmol/L), lactate 4.1 (0.5-2.2 mmol/L), TSH <0.01 (0.27-4.2 uIU/mL), fT4 4.04 (0.93-1.7 ng/dL) and was admitted to the ICU for neutropenic fever and septic shock. Computed tomography (CT) imaging of the thorax showed right lung consolidation suggesting pneumonia. Magnetic resonance imaging of the spine and CT head did not demonstrate an etiology for her weakness. She was diagnosed with thyrotoxic periodic paralysis (TPP) and treated with potassium. For severe hyperthyroidism with methimazole contraindication, she received broad spectrum antibiotics, lithium 300mg orally every 8 hours, and propranolol 10-20mg every 8 hours. Given minimal improvement in both weakness and hypokalemia after 48 hours of therapy, she was also diagnosed with refeeding syndrome and potassium repletion was intensified. The patient’s shock resolved, with slow improvement of lower extremity weakness over a two-week period and resolution of agranulocytosis and fevers. Conclusion: This rare presentation offers several distinct points regarding the patient’s care. Firstly, TPP is a rare hyperthyroidism-related hypokalemia that can cause weakening of the extremities due to a rapid intracellular shift of potassium (1) and is an important syndrome to consider on the differential for any thyrotoxic patient presenting with sudden-onset weakness. Secondly, gentle potassium repletion is recommended to prevent rebound hyperkalemia. However, our patient had both total body loss of potassium from refeeding syndrome and intracellular shift from TPP, requiring more aggressive potassium repletion to treat her paralysis than is typical for TPP alone. In settings where weakness and hypokalemia do not improve with beta blockade and gentle potassium repletion, it is important to investigate other causes of hypokalemia and consider concurrent overlapping diagnoses. Lastly, patients with methimazole-induced agranulocytosis may require alternative treatments, such as lithium to control hyperthyroidism. 1) Lin, Shih-Hua. Thyrotoxic Periodic Paralysis. Mayo Clin Proc. 2005;80(1):99-105. Presentation Date: Saturday, June 17, 2023

Gestation-suppressed serum TSH levels during early pregnancy are not associated with altered maternal and neonatal outcomes.

The aim of the study was to investigate the impact of suppressed serum TSH levels (sTSH) during early pregnancy on maternal and neonatal outcomes. In this single-centre, retrospective cohort study 1081 women were screened at 11.8 ± 2.4 weeks of pregnancy for TSH, free T4 (FT4) and TPOAb. Exclusion criteria were twin- and assisted- reproduction pregnancies, women with TSH levels >3.74 mIU/L, severe hyperthyroidism, treated for thyroid dysfunction before or after screening and gestational blood sampling <6 or >16 weeks of pregnancy. The prevalence of adverse pregnancy outcomes was compared between the study group sTSH (TSH: < 0.06 mIU/L; n = 36) and euthyroid controls (TSH: 0.06-3.74 mIU/L; n = 1045), and the impact of sTSH on pregnancy outcomes verified in logistic regression analyses. Median (IQR) serum TSH level in women with sTSH was 0.03 (0.03-0.03) vs 1.25 (0.81-1.82) mIU/L in controls and FT4 levels 18.0 (14.4-20.3) vs 14.2 (12.9-15.4) pmol/L; both P < 0.001. None of the women with sTSH had thyrotropin receptor antibodies. Compared with controls, the prevalence of TPOAb positivity (TAI) was comparable between groups (5.6% vs 6.6%; P = 0.803). The prevalence of maternal and neonatal pregnancy outcomes was comparable between the study and control group. The logistic regression analyses with corrections for TAI, FT4 and demographic parameters confirmed the absence of an association between sTSH, and the following outcomes: iron deficient anaemia (aORs (95% CI)): 1.41 (0.64-2.99); P = 0.385, gestational diabetes: 1.19 (0.44-2.88); P = 0.713, preterm birth: 1.57 (0.23-6.22);P = 0.574 and low Apgar-1' score: 0.71 (0.11-2.67); P = 0.657. Suppressed serum TSH levels during the first to early second trimester of pregnancy were not associated with altered maternal or neonatal outcomes.

Right ventricular failure due to acute pulmonary embolism associated with Graves’ disease: A case report

Background Graves' disease is a prevalent endocrine disorder characterized by diverse clinical manifestations affecting multiple organs, exhibiting varying degrees of severity. Cardiovascular system involvement is one of the most common manifestations, which include palpitation, tachycardia, cardiomyopathy, atrial fibrillation, pulmonary hypertension, or heart failure. Additionally, excessive thyroid hormone can lead to a hypercoagulable state, increasing the risk of venous thrombosis. However, thrombotic events, particularly deep vein thrombosis, cerebral venous thrombosis, or pulmonary embolism, are rare complications of Graves’ disease. Case presentation In this report, we present the case of a 53 years old woman who presented with progressively worsening dyspnea, orthopnea, paroxysmal nocturnal dyspnea, bilateral leg edema, and jaundice for 2 weeks. She had also reported a weight loss of 4 kilograms within 3 months. Upon admission to our hospital, she initially received a diagnosis of congestive heart failure with atrial fibrillation and thyrotoxicosis. Following diuretic therapy, the patient developed hypotension and severe hypoxemia. Subsequent investigation revealed acute right ventricular failure due to an acute sub-segmental pulmonary embolism, which was confirmed by computed tomography of the pulmonary artery. The patient's condition improved after resuscitation involving intravenous fluid administration to increase right ventricular preload, intravenous vasopressor infusion to elevate systemic blood pressure, management of severe thyrotoxicosis, and intravenous administration of heparin. Conclusion Graves’ disease, accompanied by hemodynamic disturbances due to acute right ventricular failure, necessitates admission to the intensive care unit for resuscitation and close monitoring. Although acute pulmonary embolism is an uncommon condition associated with Graves’ disease, it should be considered, particularly in patients who develop acute right ventricular failure.

Pitfall of Thyroid Storm Score

The thyroid storm is an emergency characterized by multiple organ failure due to severe thyrotoxicosis that is often triggered by other diseases. The diagnosis of thyroid storm is made clinically in a severe thyrotoxic patient with evidence of systemic decompensation. The Burch–Wartofsky Point Scale (BWPS) is a score that is widely used to diagnose thyroid storm, introduced by Burch and Wartofsky in 1993. In Burch–Wartofsky Point Scale, the thyroid storm diagnosis is made if there is clinically severe thyrotoxicosis with a score of 45 in a patient that has a previous history of elevated free fT3 (triiodothyronine) or fT4 (free thyroxine). But in a condition it cannot be distinguished whether a condition is caused by the effects of thyrotoxicosis or due to other diseases, then these symptoms are considered as a result of the effects of thyrotoxicosis. In the Burch–Wartofsky Point Scale, there is a pitfall. If we are accustomed to assuming a worsening of the condition in thyroid patients as a result of the effects of thyrotoxicosis, without trying to exclude the condition due to other conditions can lead to a misdiagnosis of thyroid storm. This article aims to remind us to be careful in applying diagnostic tools in diagnosing a thyroid storm.

Severe post-amiodarone thyrotoxicosis: personalized approach for radical treatment in a life-threatening condition

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract #1404976: Severe Gestational Thyrotoxicosis Complicated by Thyroid Storm in a Primigravid Patient with Hyperemesis Gravidarum in a Multiple Pregnancy

Gestational transient thyrotoxicosis (GTT) is seen in 3% of pregnancies and occurs in 30-60% of patients with hyperemesis gravidarum (HG). The incidence of thyroid storm in this setting has not yet been reported. The severity of GTT and HG is positively related to serum hCG levels. Treatment in GTT with antithyroid drugs is not routinely indicated since GTT usually is described as a disorder of spontaneous resolution without unfavorable maternal and fetal outcomes. We describe a case of severe GTT complicated by thyroid storm in a primigravid 20-year-old patient with twin gestation and HG. A 20-year-old female primigravida with twin gestation and HG presented with nausea, vomiting, altered sensorium, and weakness for four days at 14 weeks’ gestation. At 9 weeks’ gestation during inpatient management for HG, TSH < 0.01 was found. Outpatient FT4 3.1 was obtained. On current presentation, tachycardia HR 169 bpm, mild abdominal tenderness, disorientation, a repeated TSH < 0.01 resulting in Burch-Wartofsky point scale of 45 warranted MICU admission for thyroid storm management. FT4 3.3, T3 239, and hCG level 99,080 were found. Transvaginal US and positive MSSA blood cultures confirmed spontaneous septic abortion. Antibiotics were given, and dilation and evacuation were performed. FT4 and T3 improved to 2.1 and 114, respectively. TSH receptor antibody (TRAb) was found negative and thyroid US did not reveal hypervascularity or nodules. Post admission TSH 0.544 and FT4 1.02 were found. The association between HG and thyrotoxicosis was made in 1980 by Valentine et al. Estrogen and hCG levels are significantly higher in women with HG, leading to increased thyroid hormone secretion and lower TSH levels. GTT resulting from inappropriate hCG secretion is a common form of hyperthyroidism in HG. GTT usually is described as an entity with spontaneous resolution as thyroid hormones normalize by the second trimester. Treatment for GTT with antithyroid drugs is not routinely indicated and they are reserved for a minority of patients with extremely severe GTT. Fasting, hydration, and evaluation of thyroid function are recommended as the most appropriate management for GTT in HG. Genetic mutations changing lysine into an asparagine leading to an increased sensitivity of TSH receptor to hCG ultimately causing severe and prolonged GTT have been found. TRAb is recommended as a more sensitive and specific diagnostic tool to differentiate GTT and Graves’ disease. However, physiological immunosuppression tends to suppress the TRAb levels during pregnancy. Comparative follow-up studies are required to establish a final diagnosis.

Abstract #1404823: Too Much of a Good Thing: A Case of Levothyroxine Overdose

Levothyroxine is the most prescribed medication in the last decade in the United States and used commonly for treatment of hypothyroidism. Despite this, overdoses with levothyroxine are rare. Patient presentations can range from asymptomatic with a benign course to severe thyrotoxicosis. Here we present a case of an elderly woman with depression and prior suicide attempts who ingested an estimated 3000 mcg of levothyroxine in a suicide attempt. An 86-year-old female with history of hypothyroidism, major depression, bipolar disorder, mild cognitive impairment, multiple prior suicide attempts presented to the hospital 3 hours after intentional ingestion of 3000 mcg of levothyroxine. She denied co-ingestion of other medications. On physical examination, she had blood pressure of 139/76 mmHg, heart rate of 67 beats per minute (bpm), temperature 98.6 °C, respiratory rate 18 breaths/min, and oxygen saturation of 100% on room air. She denied palpitations, shortness of breath, light-headedness, or chest pain. Her neck was supple without a palpable goiter or nodules. She did not have a tremor. She was alert and oriented to time, place. She endorsed feeling depressed and hopeless which had led to the attempted suicide but now felt remorseful for the attempt. Laboratory workup was notable for lithium level 0.24 mEq/L (0.50 – 1.20 mEq/L), potassium 3.3 mEq/L (3.6 – 5.1 mEq/L), and a negative urine toxicology screen. Electrocardiogram showed normal sinus rhythm without evidence of T-wave abnormalities. Thyroid function tests revealed a thyroid stimulating hormone (TSH) of 1.087 μIU/mL (0.350 – 5.500 uIU/mL), total T3 of 360 ng/dL (80 – 180 ng/dL), and free T4 of 11.76 ng/dL (0.8 – 1.80 ng/dL). She was admitted with suicide precautions and initially treated with lorazepam as needed for anxiety. She developed tachycardia of 101 bpm on day 3 and atenolol 25 mg daily was started. Her heart rate remained in the 80 – 100 bpm range until discharge. Her free T4 trended down into the normal range on day 15 of admission and levothyroxine 50 mcg daily was restarted. She was transferred to the inpatient psychiatric unit for further management of her depression. Prior reports have described a benign course after overdose however symptoms may present in a small subset of patients. These symptoms can be mild (tremors, tachycardia, restlessness, headaches, vomiting) or severe (transient hemiparesis, coma). More severe symptoms have been described with higher doses ingested (levothyroxine 75000- 125000 mcg). Therefore, obtaining history and collateral information about the total dose ingested is important. Free thyroxine levels are trended for biochemical follow up and commonly return to normal after two weeks. TSH levels may remain suppressed well beyond the two-week period and therefore are of limited use in an acute setting. Treatment options include close clinical follow up with symptomatic treatment for tachycardia with beta-blockers. Development of severe symptoms may require levothyroxine extraction through hemodialysis or plasmapheresis.

Abstract #1395609: Moyamoya Syndrome in a Patient with Thyroid Storm; Role of Plasmapheresis?

Moyamoya syndrome is a rare cerebrovascular disorder that can be associated with Graves’ disease. We are presenting a case of young woman with Graves’ disease who developed acute neurologic symptoms. She was treated with plasmapheresis and developed cerebral edema after one procedure. A 28-year-old Hispanic female with 3 years history of Graves’ disease presented to ER with worsening symptoms of thyrotoxicosis. She was not taking antithyroid medications for the previous months. She was admitted for severe hyperthyroidism symptoms. Antithyroid medication was resumed on admission. A day later she developed sudden weakness of the right upper and lower extremities, then she became unresponsive. TSH was < 0.007 uIU/mL [0.36-3.7 mIU/mL], free T4 >8.0 ng/dl [0.76-1.46 ng/dl], total T3 2.75 ng/mL [0.6-1.8 ng/mL]. Brain imaging demonstrated occlusion of the right and left internal carotid arteries consistent with the diagnosis of Moyamoya disease. Treatment for thyroid storm with Propylthiouracil and steroids were initiated. The patient’s mental status did not improve, and plasmapheresis was initiated to improve her symptoms and neurologic outcome. Patient was hemodynamically stable during plasmapheresis with no signs of fluid shift. Several hours after the 1st session, the patient neurologically deteriorated, pupils were fixed and dilated, and corneal reflex was negative. Repeated brain imaging showed cerebral herniation, which ultimately led to brain death. Moyamoya disease is an isolated vascular disorder and a rare cause of stroke. It involves endothelial hyperplasia and narrowing of the proximal portion of the internal carotid arteries, leading to development of abnormal collateral vessels. There are several studies correlating increased thyroid hormone and auto-antibody levels with Moyamoya disease. Therapeutic plasma exchange is used to achieve rapid improvement in symptoms due to the long half-life of thyroid hormones and to eliminate the autoantibodies. It is considered a safe procedure with low incidence of adverse events. However, in patients with severe comorbidities, especially those in the intensive care unit (ICU), the prevalence of adverse events during plasmapheresis is reported to be higher. In this case, no water imbalance was reported during the procedure, and it is unknown whether the plasmapheresis played a role in cerebral edema and herniation. In general, Plasmapheresis is considered a relatively safe for patients hospitalized in ICU in literature reviews, with no reports of cerebral edema as a complication of plasmapheresis in these literatures. However, close monitoring of patients in the ICU is essential for procedure-related safety.

Acute adrenal crisis precipitated by thyroid storm in a patient with undiagnosed autoimmune polyglandular syndrome type 2.

Autoimmune polyglandular syndrome (APS) type 2 is characterized by the presence of Addison's disease (AD) along with autoimmune thyroid disease and/or type 1 diabetes. APS type 2 is known as Schmidt's syndrome when autoimmune adrenal insufficiency is associated with chronic lymphocytic thyroiditis. We report a very rare case of a 28-year-old female patient who had Schmidt's syndrome revealed by a thyroid storm (TS) concomitant with an acute adrenal crisis. The onset of AD resulted in a surgical emergency. The patient presented with cardiogenic shock and an acute abdomen. The precipitation factor was Hashitoxicosis presented as TS. This life-threatening condition was successfully reversed with aggressive medical therapy based on antithyroid drugs and intravenous glucocorticoids. This hyperthyroid phase lasted for a period of 8 months. The patient eventually developed hypothyroidism, suggesting that Hashimoto's thyroiditis was the most likely diagnosis. She was started on levothyroxine replacement therapy and remained euthyroid on levothyroxine. The case we describe had several diagnostic pitfalls that are discussed both at the start as well as during the evolution. Autoimmune diseases can appear concomitantly or succeed each other over time. The clinician must be vigilant to detect these diseases in time in order to avoid a misdiagnosis of a life-threatening emergency such as adrenal insufficiency or thyroid storm. Thyroid storm is an uncommon but life-threatening manifestation of hyperthyroidism. Diagnosis is dependent on clinical symptoms, and no specific laboratory tests are available. Glucocorticoids should be used in the treatment of thyroid storm because they have an inhibitory effect on peripheral conversion of T4 to T3. In patients who have severe thyrotoxicosis, especially in conjunction with hypotension, treatment with glucocorticoids has become standard practice because of the possibility of relative adrenal insufficiency or the possibility of undiagnosed Addison's disease. The differential diagnosis of hyperthyroidism can be challenging. Graves' disease can be discussed in view of the severity of the clinical presentation and the prolonged duration of the hyperthyroid phase. Hashitoxicosis is the initial hyperthyroid phase in chronic autoimmune thyroiditis. The hyperthyroid phase is always followed by definitive resolution, with persistent euthyroidism and no hyperthyroid relapses. Synthetic antithyroid drugs may be prescribed during the hyperthyroid phase of Hashimoto thyroiditis if the clinical presentation is severe and the duration of the hyperthyroid phase is prolonged.

Surgical treatment of a patient with stage v multinodular toxic goiter, severe thyrotoxicosis, strangulation syndrome and severe comorbidities

The authors describe thyroidectomy in a patient with multinodular toxic goiter stage V, severe thyrotoxicosis complicated by thyro-cardiac disease, strangulation syndrome and severe comorbidities. Nodular euthyroid goiter was first diagnosed in 1992, and resection of the right thyroid lobe was performed. Progressive enlargement of thyroid gland and thyrotoxicosis occurred after coronavirus infection in February, 2020. Along with progression of thyrotoxicosis and strangulation of cervical organs, the patient suffered from portal vein thrombosis, pulmonary embolism. Myeloproliferative disease with essential thrombocythemia was also diagnosed. Volume of the right and left thyroid lobes was 69 and 101.3 cm3, respectively. X-ray examination of the esophagus revealed narrowing at C6 level up to 5-8 mm. Surgery time was 2 hours, dimension of removed right thyroid lobe - 10.0×7.5×6.5 cm, left thyroid lobe - 11.0×6.5×5.5 cm, total weight - 348 g. The patient was discharged in 6 days after surgery.

Prediction-based prompt levothyroxine replacement to prevent a hypothyroid state after immune-related adverse events involving the thyroid gland.

Immune checkpoint inhibitors (ICIs) are used for various malignancies, although they frequently cause immune-related adverse events involving the thyroid gland (thyroid irAEs). We conducted a retrospective cohort study to elucidate thyroid function outcomes. Fifty of 639 patients who received PD-1 blockade therapy met criteria and were divided into the following groups: thyrotoxicosis with subsequent hypothyroidism (Toxic-Hypo, n = 21); thyrotoxicosis without subsequent hypothyroidism (Toxic, n = 9); and hypothyroidism without prior thyrotoxicosis (Hypo, n = 20). The Toxic-Hypo group developed thyroid irAEs earlier than the Toxic group (26 vs. 91 days; p < 0.001), and had higher serum free T4 levels (3.210 vs. 1.880 ng/dL; p = 0.011). In addition, positive anti-thyroglobulin antibodies (TgAbs) at thyroid irAE onset were more common in the Toxic-Hypo group (93.3%) than in the Toxic group (0.0%; p = 0.005) and Hypo group (44.4%; p = 0.007). The Toxic-Hypo group developed severe hypothyroidism and required larger levothyroxine (LT4) doses than the Hypo group (75 vs. 25 μg/day; p = 0.007). We predicted that patients with positive TgAbs who developed severe thyrotoxicosis within 4 weeks after the first ICI administration would develop subsequent hypothyroidism. We treated 4 such patients with prompt LT4 replacement, characterized by LT4 initiation after thyrotoxicosis improvement and quick dose titration. Their euthyroid state was successfully maintained, in contrast with patients receiving conventional replacement. In conclusion, rapid-onset severe thyrotoxicosis in patients with TgAbs correlated with a high likelihood of subsequent hypothyroidism. Accordingly, prompt LT4 replacement is suggested to prevent a severely hypothyroid state.

Abstract 10988: The Dynamic Duo of Electrical and Thyroid Storm Caused by Amiodarone

Case description: A 61 year-old male with a hx of CAD s/p CABG and HFrEF s/p AICD presents with a 4-day history of dizziness and shortness of breath; he was found to be in ventricular tachycardia (VT) storm. ICD interrogation was found to have 13 shocks in 24 hours. His thyroid function tests (TFT) were abnormal: TSH undetectable, elevated FT4 7.7 (0.93-1.7) and T3 246.6 (84-202) ng/dL, respectively. He was diagnosed with severe thyrotoxicosis, likely due to amiodarone-induced thyrotoxicosis (AIT) type 2 and a Burch-Wartofsky score of 50, highly suggestive of thyroid storm (TS). He was started on hydrocortisone, prednisone, propylthiouracil, and metoprolol for the TS. Procainamide drip had been initiated for VT and titrated until VT was controlled. Repeat TFTs in 48 hours showed no changes in TSH or FT4, but T3 had normalized. Procainamide and hydrocortisone were discontinued after VT frequency had decreased. Discussion: An electrical storm (ES) is a state of electrical instability characterized by multiple episodes of VT in 24 hours. In patients with ICD, it is defined as &gt;3 anti-tachycardic pacing therapies or shock. Most patient with ES have severe underlying structural heart disease with various inciting events such as thyrotoxicosis. Amiodarone is the drug of choice in VT; however, complications such as AIT should be recognized. Thyroid hormone has a direct arrhythmogenic effect on the heart through various cellular mechanisms. In our patient, amiodarone was discontinued after the diagnosis of AIT. Procainamide and antithyroid therapy were started, which subsequently controlled the VT. Resistance to therapy can occur, and more elaborate interventions such as plasmapheresis are an option to remove amiodarone, its metabolites, and free thyroid hormones. Conclusion: Amiodarone is the most efficacious medication for VT. However, it is important to recognize possible life-threatening complications of this medication, such as AIT, which itself can exacerbate VT.

ODP515 Severe thyrotoxicosis caused by subacute thyroiditis

Abstract Background Subacute thyroiditis, also named giant cell thyroiditis, painful thyroiditis, and de Quervain's thyroiditis, usually presents with neck pain or discomfort, a tender diffuse goiter and mild or moderate elevation of serum free T4 and T3 levels. Here we report a case of subacute thyroiditis patient presenting with severe thyrotoxicosis. Clinical case: A 27-year-old woman with no significant past medical history presents to the emergency room with palpitations and abnormal EKG with heart rate at 160 beats per minute. She developed a sore throat 3 days prior to the presentation, but she did not have neck pain or fever. She reports a 3-month history of hair loss, headaches and weight gain. Labs showed significantly elevated free T4 greater than 7.7 ng/dl (0.8-1.7) and free T3 level at 20.7 pg/ml (2. 0-4.8), and suppressed TSH less than 0. 01 uIU/ml (0.45-4.5) and normal ESR at 15 mm/hour. Her TPO antibody was greater than 1300 u/ml. Thyroid stimulating immunoglobulin (TSI) and TSH receptor antibody (TRab) were obtained but results were pending when she was discharged from the hospital. She has no typical clinical features of subacute thyroiditis with normal ESR and her free T3 and free T4 levels were significantly elevated. She was discharged on Methimazole and Propranolol and to do neck ultrasound as outpatient and follow-up TSI and TRab results and repeat free T4 and T3 in 1 week. Her neck ultrasound revealed mild hypervascularity but no Graves’ features. Her TSI and TRab were negative and free T4 level had no improvement even on significant dose of Methimazole. All the findings argue against Graves’ disease, but support subacute thyroiditis. Then Methimazole was discontinued and Prednisone was started at 20 mg daily and quickly taper to 5 mg daily in 2 weeks then stopped. After on Prednisone for 3 weeks, her free T4 was close to normal at 2. 0 ng/dl, T3 normal at 120 ng/dl, although TSH is suppressed. After stopped Prednisone for 2 weeks, her free T4, T3 and TSH were all back to normal. She is currently euthyroid without any medication at 5 months after her initial presentation. Conclusion Treatment of patients with subacute thyroiditis is pain relief with NSAID or Prednisone when NSAID is not effective. Anti-thyroid medications are rarely effective even in subacute thyroiditis patient with thyroid storm. Our case illustrated the role of corticosteroids in the treatment of subacute thyroiditis patient with severe thyrotoxicosis. Neck ultrasound and thyroid antibodies including TSI and TRab are critical to make a correct diagnosis in subacute thyroiditis patient with severe thyrotoxicosis. Presentation: No date and time listed

PSAT239 Pregnant Patient With a History of Methimazole-Induced Agranulocytosis Presenting With Hyperthyroidism: A Case Report

Abstract Background Pregnancy has a profound impact on the thyroid gland and its function. Severe thyrotoxicosis can lead to many complications and endanger the mother or fetus. Antithyroid drug (ATD), at its lowest possible dose, should be given. However, one of the complications of treatment include agranulocytosis which is a rare but serious allergic event with a prevalence of 0.1 to 0.5 percent. Thus, alternative treatment should be prescribed because a cross-reaction between ATDs was observed in 15.2% of patients in a study. Insufficient data is available regarding the use of these medications in pregnant patients with history of drug-induced adverse reactions. There are other feasible alternative treatments but are contraindicated in pregnancy. Case We report a 29-year old patient gravida 5 para 4 at 10 weeks age of gestation at the time of consult presenting with palpitations. She is a known case of Graves’ disease for 7 years and maintained on Methimazole. She was admitted a year prior consult as a case of impending thyroid storm; Methimazole-induced agranulocytosis. Initially, maintained on Lithium but shifted back to Methimazole without a physician's advice and later on, discontinued the medication upon knowledge of pregnancy. She presented on her first trimester of pregnancy with palpitations and elevated free thyroxine (T4) at 71.29 pM (normal range: 11-24 pM). She was started on Propylthiouracil 50 mg/tablet 1 tablet three times a day. On her second trimester, no reported symptoms of hyperthyroidism and/or agranulocytosis such as fever or sore throat. Thyroidectomy was offered at this time explaining the risks and benefits but she strongly refused. Free T4 was then maintained at a value slightly above the upper normal limit. Propylthiouracil was also shifted to Methimazole 5 mg/tablet 1 tablet once daily and revised to 1 tablet every other day on the third trimester of pregnancy. Delivery was uneventful and the newborn was evaluated by a pediatrician with unremarkable findings. Four weeks postpartum, no noted symptoms of hyperthyroidism and/or agranulocytosis. Free T4 was noted within the normal range at 18.84 pM. Alternative treatment was offered due to the risk of ATD-induced agranulocytosis. Conclusion Hyperthyroidism in pregnancy is associated with a variety of complications for the mother and fetus. Three effective treatment options include ATD, thyroidectomy or RAI therapy. But, not all are relatively safe for pregnancy. In initiating ATD, cross-reaction between medications should be considered especially for patients with history of adverse reaction, such as agranulocytosis, which can be life-threatening. However, there are limited studies in the management of this specific case. Treating physician and patient should discuss each of the options, including the benefits, drawbacks and side effects. Keywords: Hyperthyroidism, Graves’ disease, Pregnancy, Agranulocytosis Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP523 Thyroid Storm in a Patient With Alemtuzumab Induced Graves’ Disease

Abstract Background Thyroid storm (TS) is a rare and life-threatening medical emergency, most commonly caused by Graves’ disease (GD). GD can beinduced by immune reconstitution therapy (IRT) such as Alemtuzumab (ALZ), a humanized monoclonal antibody against CD52, which is shown to be effective in the treatment of relapsing-remitting multiple sclerosis (RRMS). Evidence shows that ALZ induced GD may be less aggressive than conventional GD. Below we present a rare case of thyroid storm developing in a patient with ALZ induced GD. Clinical Case A 39 year-old female non-smoker, known to have RRMS, wasstarted on ALZ. Presented to our emergency room13months later with palpitation, diarrhea and oligomenorrhea. Found to have TSH of 0. 007 mIU/L (0.250-5), T4 50 pmol/L (11.5- 22.7), thyroid scan demonstrated diffusely enlarged thyroid gland with increased tracer uptake compatible withGD. Our impression was ALZ- induced GD (not in thyroid storm),she wasstarted on carbimazole and propranolol and discharged home. Neurology team gave hera second cycle of ALZas she was euthyroid on carbimazole. One month later, the patient presented to our emergency room with nausea and vomiting. On examination, she was febrile 38.2°C, tachycardic reaching 140 beats/min (regular). Her blood pressure was 138/87 mmhg. The patient was agitated, anxious, alert and oriented. She was diaphoretic with mild peripheral oedema and had pulmonary crackles. The thyroid was diffusely enlarged with no signs of graves’ ophthalmopathy, or pretibial myxedema. On the Burch-Wartofsky Point Scale for thyroid storm, she scored 60. The patient was admitted to the intensive care unit (ICU), with endocrinology and neurology consultation. Laboratory investigation revealed TSH of 0. 009 mIU/L, T3 26.5 pmol/L (3.39-5.82) T4 65 pmol/L, positive thyroid peroxidase antibody 183 units (&amp;gt;100 positive). Despite treatment with maximum dose of carbimazole, B-blocker, hydrocortisone, and potassium iodide her T4 was not improving, and her liver function was deteriorating. Finally, she underwent total thyroidectomy. Three days post total thyroidectomy, the patient clinically improved. Steroids were stopped and the B-blocker dose was gradually tapered. She was then maintained on Levothyroxine. Conclusion It is thought that ALZ- induced GD behaves less aggressive than the conventional GD as spontaneous and/or drug-induced remission may be more likely. However, physicians should be aware that severe thyrotoxicosis and thyroid storm can happen which required prompt recognition and aggressive therapy. Presentation: No date and time listed

ODP524 Thyroid Storm Precipitated by COVID-19 Infection: A Case Report

Abstract Background Thyroid storm is an endocrinological emergency caused by severe thyrotoxicosis. COVID-19, caused by the novel coronavirus SARS-CoV-2, is known to cause thyroid-related complications of subacute thyroiditis but the occurrence of thyroid storm is rare. The use of first line therapies for thyrotoxicosis/thyroid storm, such as thioamides, radioactive iodine, and surgery, may be precluded by leukopenia, hemodynamic instability, and liver failure, which are commonly seen in severe COVID-19 infection. The necessity for isolation creates a challenge for surgical intervention for these patients. Here we present a unique case of thyroid storm secondary to Graves’ disease, reactivated by COVID-19 infection and managed with therapeutic plasma exchange (TPE). Clinical Case A 56-year-old African American female with history of hyperthyroidism for the past 13 years, presented to the emergency department with sore throat and fatigue for one week prior. On arrival, she was febrile with temperature of 101.1° Fahrenheit, tachycardic with heart rate of 163 bpm and tachypenic with respiratory rate of 41 rpm. Patient had bilateral orbitopathy, tender thyromegaly, thyroid bruit and fine tremors. She also had atrial fibrillation, right-sided heart failure, acute liver failure. Nasopharyngeal COVID-19 testing was positive; laboratory tests revealed TSH &amp;lt;0. 01 uIU/mL (n 0.450 - 5.330), free T4 &amp;gt;5.60 ng/dL (n 0.45 - 1.8), direct bilirubin 1.8 (n 0.1-0.3 mg/dl), mild transaminitis and INR 2.21 (n 0.9-1.1). White blood cell count was 5.4 K/uL (n 4.5-11.5) with 50.8% neutrophils (n 31-76%). Ultrasound of abdomen revealed decompensated cirrhosis with ascites. The Burch-Wartofsky score was 75 points, indicative of thyroid storm. Acute liver failure precluded the use of thioamides; due to the severity of the hyperthyroidism, ablation was not considered. The use of Lugol's iodine was held pending surgical clearance due to active COVID-19 infection. Eventually, patient underwent a total of four sessions of TPE. With each session free T4 levels decreased: 4.12 ng/dl, 2.73 ng/dl, 2.52 ng/dl, and 1.53 ng/dl, respectively. Six days after the last TPE, patient developed complications related to COVID-19 infection and expired before undergoing total thyroidectomy. Conclusion This is a complicated case of a patient with thyroid storm, acute liver failure in the setting of COVID-19 infection. SARS-CoV-2 virus may not only be a trigger for thyroid storm but also represents a challenge in the management of thyroid disease. During TPE, patients’ plasma is extracted from the components of the blood and a colloid replacement solution is infused back. Thyroxine binding globulin bound to thyroid hormones is removed with plasma and colloid replacement provides new binding sites for circulating free thyroid hormone. TPE is effective but rarely used in the past and can be considered as therapeutic for thyrotoxic patients with COVID-19 infection, in whom conventional methods of treatment are not feasible options. Presentation: No date and time listed

LBSAT236 A Case of Immune Checkpoint Inhibitor Pembrolizumab Induced Simultaneous Rare Endocrinopathies, Type 1 DM (presenting As DKA) And Grave's Thyrotoxicosis, With Evidence Of Autoimmunity Development.

Abstract Introduction Pembrolizumab is a novel immunotherapeutic monoclonal antibody directed against PD-1 (programmed death receptor 1), which has been linked to endocrinopathies. We present a rare case of type 1 DM and Grave's disease noted in setting of Pembrolizumab use. Case presentation A 56 year old female with history of Hodgkin's lymphoma (being treated with Pembrolizumab), heart failure and type 2 DM was sent to the ED from oncology infusion clinic for labs concerning for DKA. She endorsed fatigue, light-headedness, polydipsia and polyuria. She had moderate to severe DKA with bicarbonate 9 mmol/L (22 - 31), anion gap 29 mmol/L (7 -17), venous Ph 7.16 (7.30 - 7.40), beta hydroxybutyrate 9.4 mmol/L (0 - 0.3) and blood glucose 451 mg/dL (70 - 100). She was admitted to the ICU and started on insulin drip. She had a 20 year history of type 2 DM and prior to this episode had been managed on Metformin 500 mg daily alone with good glycemic control (HbA1c 5.7 - 7.1%) and had never had DKA before. Of note, she also reported recent 75 pound weight loss which she attributed to lifestyle changes. GAD65 antibody assay was positive 5.49 nmol/L (&amp;lt;=0. 02 nmol/L). She was discharged on a basal bolus insulin regimen and continues to follow up with Endocrinology. On admission, she had thyrotoxicosis with TSH 0. 06 uIU/mL (0.50 - 5.70), fT4 1.8 ng/dL (0.9 - 1.7), and total T3 99 ng/dL (80 -200) while clinically euthyroid. Repeat TFTs in one week were consistent. TSI was elevated 1.8 (&amp;lt;=1.3 TSI Index). 10 days later, labs showed improvement TSH 0. 09 uIU/mL, fT4 1.2 ng/dL and total T3 130 ng/dL. As she was clinically euthyroid and noted to have improving levels, she was managed conservatively. However, one additional one month later, tests were repeated and showed progression to hypothyroid state - TSH 44.23 uIU/mL and fT4 0.4 ng/dL. She was started on Levothyroxine supplementation. Repeat testing showed normalization of TSH. Discussion Our patient had long standing history of well controlled Type 2 DM and no history of thyroid abnormalities yet presented with moderate to severe DKA and thyrotoxicosis due to Grave's disease shortly after initiating immune checkpoint inhibitor therapy. GAD65 antibody and TSI panel were positive indicating development of autoimmunity. Although rare, development of rare endocrinopathies such as insulin deficient diabetes and Grave's disease are important side effects of immunotherapy. Patients being treated with immunotherapeutic agents should be monitored closely with serial metabolic panel testing for the first twelve weeks after starting therapy. In addition, a low threshold should be maintained for testing for additional thyroid related endocrinopathies. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP461 Amiodarone Induced Thyrotoxicosis With Severe Cardiac Disease Refractory to Medical Therapy and Plasmapheresis

Abstract Introduction Management of amiodarone induced thyrotoxicosis (AIT) presents the clinical challenge of differentiating between the two subtypes: Type I AIT, characterized by increased hormonal biosynthesis, and Type II AIT, a destructive thyroiditis since the treatment differs. We present a case of a patient with severe cardiac disease on long-term amiodarone who presented with thyrotoxicosis who was minimally clinically symptomatic despite significant biochemical thyroid function abnormalities and refractory to all medical interventions, including plasmapheresis, ultimately requiring total thyroidectomy. Case Description An 82 year-old-male with severe cardiac disease including coronary artery disease with prior CABG, EF of 25-30% with ICD, and atrial fibrillation on amiodarone, presented to the hospital due to palpitations and multiple shocks delivered by patient's ICD. EKG revealed atrial fibrillation and the ICD demonstrated episodes of sustained ventricular tachycardia. The Burch-Wartofsky score was 25. He had palpitations, tremors, and atrial fibrillation but no thyromegaly, thyroid bruits or thyroid eye disease. Thyroid function testing was TSH &amp;lt;0. 01 ulU/mL (Normal 0.3 - 4.5 ulU/mL), FT4 5.29 ng/dL (Normal 0.5- 1.26 ng/dL). Thyroid ultrasound showed multiple sub-centimeter nodules without increased vascularity. Since patient had characteristics of both AIT subtypes, patient was started on treatments for both including hydrocortisone 100 mg TID, Lugol's Iodine 10 drops TID, methimazole 20 mg QID, propranolol 20 mg QID, cholestyramine 4g BID, and lithium 300 mg TID. Despite extensive medical management, the patient's thyroid levels remained grossly elevated with FT4 nadir of 4.37 ng/dL. Plasmapheresis was initiated every 1-2 days for a total of 6 treatments and the patient's FT4 improved to 3.52 ng/dL before increasing again. During this treatment period, the patient remained relatively asymptomatic but had severe cardiac disease which further complicated the urgency for thyroidectomy. Ultimately, he underwent a total thyroidectomy that caused the resolution of the thyrotoxicosis. He was started on levothyroxine and subsequent pathology revealed multi-nodular goiter with lymphocytic thyroiditis. Discussion This challenging case of amiodarone induced thyrotoxicosis in a patient with severe cardiac disease, refractory to extensive medical therapy including plasmapheresis and requiring total thyroidectomy, highlights the difficulty in management of AIT. Management of refractory AIT involves differentiating between the two clinical subtypes with the goal of expediently achieving a euthyroid state to avoid severe cardiac complications and mortality. This case was particularly challenging since our patient had relatively stable clinical status despite chemical thyrotoxicosis with characteristics of both subtypes of AIT. It was challenging to optimize a patient's thyroid levels prior to thyroidectomy, due to severe cardiac disease and persistent thyrotoxicosis. Ultimately, our patient was refractory to medical treatments for both AIT subtypes and plasmapheresis. The resolution of thyrotoxicosis was not achieved until he underwent total thyroidectomy Presentation: No date and time listed

OR11-3 Steroid Treatment in the Management of Destructive Thyrotoxicosis Induced by PD1 Blockade

Abstract Background Destructive thyroiditis is the most common endocrine immune related adverse event (iRAEs) in patients treated with anti-PD1/PD-L1 agents. Given its self-limited course, current guidelines recommend no treatment for this iRAE. Nevertheless in patients with enlarged thyroid volume and a poor performance status, thyrotoxicosis may be particularly severe and harmful. Aim of the study is to evaluate if steroid treatment might be useful in improving thyrotoxicosis in subjects with a poor performance status. Methods We conducted a case-control study, comparing the course of thyrotoxicosis of 4 patients treated with oral prednisone at the dosage of 25 mg/d (tapered to discontinuation in three weeks) and an enlarged thyroid volume to that of 8 patients with similar thyroid volume who were left untreated. Results No difference was found between the two groups at the onset of thyrotoxicosis (time 0) in demographic characteristics and in the levels of thyroid hormones. The levels of thyroid hormones were lower in subjects treated with prednisone compared to those untreated at time 7, 14, 21, 28, 35, 42, 60 and 90 days (P&amp;lt;0.05 at each time). The median time to remission of thyrotoxicosis was 24 days in patients treated with steroids and 92 days in untreated patients (P&amp;lt;0.001). At 6 months, the rate of evolution to hypothyroidism was similar in the 2 groups (4/4 in steroid group vs 7/8 in untreated group, P=0.74) and no difference was found in tumor progression (Progression free survival in treated group 5.1 months vs 5.0 months in untreated patients, P=0.89). Conclusion A short period of prednisone therapy is useful to restore more quickly euthyroidism in patients with a poor performance status and a severe destructive thyrotoxicosis induced by PD-1 blockade. This treatment does not impair the efficacy of immunotherapy. Presentation: Sunday, June 12, 2022 11:30 a.m. - 11:45 a.m.

ODP447 A Case of Hidden Grave's After Total Thyroidectomy

Abstract Introduction A Sub-sternal goiter is a condition where there is an abnormal enlargement of thyroid gland that extends into the chest. The most commonly accepted definition is when &amp;gt;50% of the volume of a goiter extends into the thoracic inlet. We present an interesting case of a Sub-sternal goiter emerging as a cause of Grave's disease, years after Total Thyroidectomy. Clinical Case The Patient is a 75 year old female with PMH of endometrial cancer, who initially underwent total thyroidectomy due to Thyromegaly causing dysphagia, and was started on Levothyroxine therapy after surgery. Three years later, a sub-sternal mass, was incidentally found via CT chest, which measured 3.7cm in largest diameter. Nuclear Medicine uptake and scan confirmed thyroid origin of this mass with an increased uptake but no percentage uptake was provided. Patient's Thyroid functions tests remained within normal range on levothyroxine. But over the next 2 years,the patient needed declining doses of LT4, then became euthyroid, off of levothyroxine and eventually became hyperthyroid, with positive Thyroid stimulating immunoglobulin. She also developed symptoms of tremors and tachycardia, and developed Atrial fibrillation as well. Noophthalmopathyor dermopathy was found on exam. Repeat CT chest showed the sub-sternal goiter had increased to a partially calcified mass of 5.6 cm. NM uptake scan showed 38.6%, at 24 hour, generalized uptake of this mass. Radioactive Iodine Ablation was performed with 30.1mCi and she subsequently became hypothyroid again until 1 year ago when she had episodes of A-fib again, and was found with TSH of 0. 09(0.45-5.33mIU/L) and FT40.9 (0.6- 1.2 ng/dl) and free T3 of 6.4 (pg/dl), off of levothyroxine. NM uptake and scan was repeated which indicated recurrence of Grave's disease from the same source. The Patient chose to initiate Methimazole therapy while contemplating surgical resection. Clinical Lesson: This is a unique case of Sub-sternal goiter, presenting as grave's disease, years after total thyroidectomy. This case emphasizes on the importance of identifying and treating sub-sternal goiter, as it can cause severe Grave's disease and thyrotoxicosis. Especially in this case, since Grave's caused by this sub-sternal goiter was recurrent after Radioactive iodine ablation. Presentation: No date and time listed