History Of Graves Research Articles

12337 Nivolumab Induced Secondary Adrenal Insufficiency And Hypothyroidism In A Patient With Graves’ Disease: A Case Report

Abstract Disclosure: F. Sajid: None. J. Kaur: None. A. Zatsepina: None. M. Khan: None. C.A. Resta: None. Introduction: We present a case of a patient with Graves’ disease who developed concurrent secondary adrenal insufficiency (SAI) and primary hypothyroidism while undergoing treatment with nivolumab for non-small cell lung cancer (NSCLC). This case sheds light on the immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) therapy. Case Presentation: A 63-year-old woman with a history of Graves’ disease and NSCLC undergoing neoadjuvant chemoimmunotherapy was admitted with hyponatremia. She was diagnosed with Graves’ disease a year before and was treated with methimazole (MMI). When she was diagnosed with Graves’ disease, her TSI was 1.64 IU/L (<0.55). Before starting nivolumab, TSH had normalized at 0.5 MCIU/mL on MMI therapy. She started nivolumab 3 months before admission. One month after starting nivolumab, her TSH was <0.01. By the time she was admitted, she had severe hypothyroidism and SAI with sodium 116 mmol/L (135-149), TSH 40.34 mIU/mL (0.39-4.08), free T4 <0.25 ng/dL (0.8-1.8), TSI 21.2 IU/L (0.00-0.55) Total Cortisol 0.4 ug/dL (6.7-27.6), AM Cortisol 0.6 ug/dL, ACTH <1.5 pg/mL (7.2-63.3), LH 75.5 IU/L (7.7-58.5), and FSH 179 IU/L (25.8-134.8). MMI was discontinued due to hypothyroidism. She was started on replacement therapy with levothyroxine and hydrocortisone. Subsequent sodium levels normalized. Discussion: Nivolumab has emerged as a promising immunotherapy for NSCLC. Our patient developed irAEs following nivolumab treatment. Notably, this case represents only the third documented case to our knowledge of both primary hypothyroidism and secondary adrenal insufficiency occurring post-nivolumab treatment. Workup for our patient revealed two irAE’s. She developed primary hypothyroidism and isolated ACTH deficiency with other pituitary function remaining normal. The pattern of thyroid profile over time was consistent with thyroiditis due to ICI therapy. TSI increased, ruling out remission from Graves’ disease. Even after discontinuing methimazole, she remained hypothyroid. Hence, in this case, ICI effectively acted as definitive therapy for her Graves’ disease. Conclusion: This case sheds light on the intricate interplay between nivolumab therapy, pre-existing autoimmune conditions such as Graves’ Disease, and the emergence of irAEs. This case underscores the importance of vigilant monitoring of serum sodium levels, and thyroid and pituitary function tests in patients undergoing immunotherapy. Presentation: 6/1/2024

7699 Unanticipated Harmony: PD-L1 Inhibitor Treatment for Urothelial Cancer Resolving Graves' Disease in a Patient - A Case of Immune Modulation Surprises

Abstract Disclosure: K. Tiwari: None. C.A. Resta: None. Introduction: Programmed death ligand 1(PD-L1) inhibitors constitute a class of immune checkpoint inhibitors (ICI) employed in treating various cancers. Thyroid-related immune-related adverse events (irAEs), such as hypothyroidism, are found to be in 3.9% of patients with PD L1 treatments. This case explores a unique scenario where a patient with pre-existing Graves' disease, undergoing PD-L1 inhibitor therapy for cancer, experienced an unexpected sequence of events leading to the default treatment of Graves' disease and subsequent progression to hypothyroidism. Case Presentation: A 59-year-old male, who had been effectively managed on methimazole for Graves' disease over two years and had chosen not to pursue definitive therapy for the condition, presented with tremors and a bilaterally enlarged thyroid gland during treatment for urothelial carcinoma. Laboratory findings included a TSH of 0.03 mIU/L (nl 0.40-4.50 mIU/L), fT4 of 3.4 ng/dL (nl 0.8-1.8 ng/dl), and tT3 of 284ng/dl (nl 76-181 ng/dl). The patient had recently started treatment with Avelumab, a PD-L1 inhibitor, as maintenance therapy following 4 cycles of gemcitabine/cisplatin cycles. Concerned about worsening Graves' disease, the methimazole dose was increased, and follow-up labs were performed after three weeks. These results showed low-normal fT4 of 0.8 ng/dL, TSH of 1.01 mIU/L(N), and low T3 of 58 ng/dL. TSI was mildly elevated at 168%. Due to rapidly changing thyroid function tests and suspicion of thyroiditis, methimazole was stopped. A PET scan a week later indicated diffuse thyroid uptake consistent with thyroiditis. Repeat labs 10 days later revealed a TSH of 67.36 mIU/L(H) and fT4 of 0.4 ng/dL(L), indicative of overt primary hypothyroidism. The patient exhibited symptoms including fatigue, constipation, and cold intolerance. The patient was initiated on levothyroxine therapy to address overt primary hypothyroidism, likely secondary to destructive thyroiditis from ICI. Discussion: Thyroid irAEs are typically incidentally discovered during routine monitoring of ICI treatment. It includes thyrotoxicosis, subclinical hypothyroidism, and overt hypothyroidism. These events commonly occur in patients lacking pre-existing thyroid conditions. In contrast, our patient, with a history of Graves' disease, experienced resolution of Graves' disease following treatment with PD-L1 inhibitor use with subsequent progression to hypothyroidism. Conclusion: This case emphasizes the importance of recognizing atypical presentations of thyroid irAEs in individuals with pre-existing thyroid disorders undergoing ICI treatment. Presentation: 6/3/2024

7876 Complex Complications of Thionamide Therapy in One Patient: Methimazole-Induced Agranulocytosis and PTU-Induced ANCA-Vasculitis

Abstract Disclosure: E. Zweibach: None. A. Chang: None. Introduction: Thionamides, including methimazole and propylthiouracil (PTU), are essential for treating Graves' disease but can cause serious side effects such as agranulocytosis and ANCA-vasculitis. Although agranulocytosis itself is quite uncommon, the incidence of ANCA vasculitis is even more infrequent, making combination of conditions particularly exceptional. We present a unique case of a Graves' disease patient who suffered both complications: agranulocytosis due to methimazole and ANCA vasculitis from PTU, with successful resolution of both the clinical signs and laboratory findings following drug discontinuation. Case: 61-year-old female with a history of Graves' disease previously managed with methimazole but discontinued due to agranulocytosis, presented with lower extremity swelling, atrial fibrillation with RVR, and high output cardiac failure. Laboratory tests showed hyperthyroidism (TSH 0.008, Free T4 3.07), leading to a diagnosis of thyroid storm. Patient was started on PTU inpatient and discharged with this medication to home. Eight months later, the patient developed alarming signs including gross hematuria, oral ulcers, widespread muscle pain, found to have AKI with Cr of 2.79 and hospitalized for further eval. While hospitalized, the patient was found to have a range of complications including leukopenia with normal granulocyte count, anemia, AKI, proteinuria, and microscopic hematuria. Rheumatological evaluation showed +ANA and a high ANCA titer >1:1280, along with elevated levels of MPO and PR-3, and reduced complement levels. These symptoms and laboratory findings led to a diagnosis of ANCA vasculitis induced by PTU, resulting in the cessation of this medication. Following the discontinuation of PTU there was a notable improvement with normalization of serum Cr and resolution of proteinuria within 1.5 months. Concurrently, MPO and PR-3 levels began to decrease, and her hematological abnormalities resolved. During this period, her Free T4 levels gradually increased, leading to the administration of radioactive iodine for the treatment of her Graves' disease. Discussion: This case underscores the complexities in treating a patient with Graves' disease highlighting the unpredictable and severe side effects of antithyroid drugs like agranulocytosis and ANCA vasculitis. We report the first documented case of sequential thionamide-induced complications: agranulocytosis with methimazole, followed by ANCA vasculitis with propylthiouracil. Although both can arise from immune responses to these medications, they are distinct in their pathophysiology and are not associated with one another. The unpredictable nature of these side effects complicates prevention. Educating patients to promptly report any unusual symptoms and immediate medical intervention with drug discontinuation are key to managing these adverse reactions effectively. Presentation: 6/1/2024

7596 Thyroid Function Tests in Breast Cancer Patients Following Immune Checkpoint Inhibitor Treatment: What Happened in a Population with Preexisting Thyroid Dysfunction?

Abstract Disclosure: M. Villanova: None. L. Min: None. Introduction: Thyroid dysfunction occurs commonly following immune checkpoint inhibition, but the etiology remains unclear. Immune checkpoint inhibitor (ICI) is not contraindicated in patients with a preexisting thyroid dysfunction, but little is known about the impact of ICI on thyroid function tests (TFTs) in this setting. This study sought to define TFTs abnormalities following ICI treatment in patients with previous thyroid dysfunction. Methods: We performed a retrospective cohort study of thyroid dysfunction in patients with breast cancer undergoing anti-programmed cell death protein-1/ligand-1 therapy from May 2016 to Dec 2023. Results: A total of 30 patients were included with a mean follow-up of 18 ± 12 months. Two patients (7%) had a history of Graves’ disease, 4 patients (13%) had a post ablative hypothyroidism, and 3 patients (10%) had a post-surgical hypothyroidism. The etiology of the hypothyroidism was not further specified in the remain cases (70%). Twenty-three patients (77%) were treated with levothyroxine at baseline at the mean dose of 1.31 ± 0.68 mcg/kg. Baseline TFTs were available in 27 patients (90%). Twenty-four patients (80%) had at least one TFTs abnormality after initiating ICI treatment. Subclinical hypothyroidism (n = 11) was the most common abnormality, followed by overt thyrotoxicosis (n = 10), subclinical thyrotoxicosis (n =7), and overt hypothyroidism (n = 7). Thirteen out of 16 patients with normal baseline TFTs developed at least one TFTs abnormality after initiating ICI treatment. Subclinical hypothyroidism (n = 6) and overt thyrotoxicosis (n =6) were the most common alterations, followed by subclinical thyrotoxicosis (n = 5), and overt hypothyroidism (n = 3). Three patients with post-ablative hypothyroidism had normal baseline TFTs. Among these, one patient developed an overt thyrotoxicosis, one patient developed a subclinical hypothyroidism followed by overt thyrotoxicosis and one patient had no TFTs alterations. One post-operative hypothyroid patient had a normal baseline TFT and developed a subclinical hypothyroidism followed by overt thyrotoxicosis. Twenty-five patients (83%) were on levothyroxine at the last follow-up at the mean dose of 1.41 ± 0.60 mcg/kg. The dose was higher than that at baseline but did not reach statistical difference (Student T test, P = 0.059). Levothyroxine dosage was adjusted in 16 patients (53%) and 25 patients (83%) achieved normal TFTs at the last follow-up. Conclusion: ICI treatment related TFTs abnormalities were common in patients with preexisting thyroid dysfunction. There were multiple distinct phenotypes. The mechanisms underlying the TFTs abnormalities is not clear. Destructive thyroiditis, medication adherence, or interference with TFT assay by ICI are among the possible etiologies. ICI is not contraindicated in this group of patients but their TFTs should be monitored closely. Presentation: 6/1/2024

9398 Early Identification of Impending Thyroid Storm Leading to Improved Thyrotoxic Induce Cardiomyopathy

Abstract Disclosure: D.H. Sacoto: None. D. Patel: None. A. De Rosairo: None. K. Madani: None. B. Singh: None. A. Bonilla Campos: None. R. Belokovskaya: None. F. Alberto A.: None. Introduction: Heart failure can be the leading presentation in 6% of thyroid storm cases and is the leading cause of death, particularly in elderly patients. However, its importance lies in symptom control and heart function reversibility once the euthyroid state is achieved. We present a caseof thyroid storm-induced atrial fibrillation (Afib) leading to severe systolic dysfunction. Case: A 61-year-old female with a history of Graves’ disease (GD) presented to the ED with two months of palpitations and one week of shortness of breath. There were bibasilar lung crackles, irregular heart rhythm, pedal edema, and thyromegaly at the examination. EKG was consistent with Afib with rapid ventricular response (123-135 beats per minute); She was tachypneic (respiratory rate: 40 per minute) and hypoxemic (87% O2 saturation), which required bilevel positive airway pressure. Otherwise, hemodynamically stable (BP: 127/106 mmHg). Laboratories showed negative troponin T (<0.010 ng/mL, n <0.01 ng/mL). However, elevation of Pro-B-type natriuretic peptide (6000 pg/mL, n <125 pg/mL), an x-ray displaying bibasilar pleural effusions and an echocardiogram demonstrating a severely reduced ejection fraction (EF) (21%, n 50-70%), myocardial perfusion scan was normal. Thyroid evaluation showed a suppressed TSH (<0.01 uIU/mL, n 0.27-4.20 uIU/mL) with elevated free T4 (5.8 ng/dL, n 0.9-1.8 ng/dL), free T3 (202 ng/dL, n 2.0-4.4 ng/dL), and TSI (8.25 IU/L, n 0-0.55 IU/L). A thyroid ultrasound revealed increased vascular flow on the left thyroid lobe. A Burh-Schakowsky score of 45 points was consistent with impending thyroid storm. She was started on methimazole, cholestyramine, and propranolol. Three months follow-up, she was asymptomatic, TSH normalized (4.12 uIU/mL), and mild improvement of cardiac EF 25%. Discussion: A thyroid storm in the setting of GD often presents after precipitating factors such as surgery, infection, or, as in our case, anti-thyroid medication non-compliance. Increased thyroid hormone levels upregulate cardiac β receptors, enhancing sensitivity to sympathetic innervation. These can shorten the refractory period of cardiomyocytes, leading to tachyarrhythmias, with Afib occurring in 20% of patients. Chronic tachycardia finally impairs left ventricle function, with heart failure as an outcome. A high index of suspicion and the ability of early diagnosis of impending thyroid storm is critical since the first laboratory confirmation is often delayed, and second, either anti-thyroid medication, radioactive iodine ablation or thyroidectomy, in addition to non-selective beta-blockers, can reverse cardiac dysfunction and lead to clinical improvement as early as 12 -Twenty-four hours of medical treatment. In our case, the early diagnosis and treatment of thyroid storm, in addition to the rate control prevented a deadly outcome and contributed to the improvement of heart failure. Presentation: 6/1/2024

12609 Navigating The Therapeutic Challenge Of Post-surgical Hypoparathyroidism And Refractory Hypocalcemia

Abstract Disclosure: D. Fawcett: None. A. Domingo: None. Introduction: Post-surgical hypoparathyroidism poses a challenge due to calcium metabolism disturbances, ranging from mild to life-threatening complications. Despite advancements, vigilant monitoring and tailored interventions are vital for optimizing outcomes. Refractory hypocalcemia, resistant to standard therapies, underscores the need for specialized care to prevent prolonged hospitalization and morbidity. Case description: A 68-year-old woman with a history of Graves' disease and parathyroid carcinoma underwent total thyroidectomy and parathyroidectomy in January 2024. She presented to the emergency department for the second time with a recurrence of bilateral hand and perioral paresthesias, along with numbness, tingling, and weakness throughout her body. Notably, she had a prior hospital admission with similar symptoms and was discharged on calcium carbonate, magnesium, calcitriol, and vitamin D3. Vital signs were not provided. Initial laboratory workup revealed a calcium level of 4.3, with corrected calcium at 5.8, and magnesium levels at 1.8, supplemented with magnesium oxide. A 24-hour urine calcium test, vitamin D, and malabsorptive workup for celiac disease were unremarkable. Immunoglobulin A was low; however, tissue transglutaminase IgA and anti-gliadin antibodies were negative. An electrocardiogram showed a normal sinus rhythm with QT prolongation to 570 ms. Despite resuming her home regimen, her calcium level remained low, prompting initiation of calcium infusion. Consultations with endocrinology and nephrology were made, necessitating close monitoring and uptitration of calcium and vitamin D supplements for achievement and maintenance of low normal calcium levels. High doses of 3g TID of calcium and calcitriol 2mcg PO TID allowed for symptom control and discharge with outpatient follow-up with endocrinology and nephrology. Conclusion: Supplemental therapy with calcium and vitamin D analogues is standard for managing post-surgical hypoparathyroidism. Early identification and adequate management prevent hypocalcemia-related complications, including tetany, seizures, and cardiovascular anomalies such as QTc prolongation, as seen in our patient, which can result in torsade de pointes. Multidisciplinary care alongside nephrology was paramount. Serum calcium should be maintained in the low normal range, and 24-hour urine calcium excretion should also be closely monitored. Daily hydrochlorothiazide can be used to prevent hypercalciuria. In recurrent cases, as in our patient, titration of calcium and vitamin D analogues is imperative. Long-term consequences, including renal dysfunction, osteoporosis, and increased cardiovascular risk, underscore the necessity for timely diagnosis and management. Presentation: 6/2/2024

Pretibial Myxedema in a Hypothyroid Patient with Grave’s Disease: A Case Report

Pretibial myxedema, a rare dermatological manifestation primarily associated with Graves' disease, presents as nonpitting edema, nodular, or plaque-like lesions on the lower legs due to accumulation of hyaluronic acid. We present the case of a 42-year-old woman with a history of Graves' disease who developed dark plaques and indurated skin lesions on her shins, extending to the dorsal feet. Diagnosed with Grave’s disease 20 years prior, she underwent subtotal thyroidectomy following antithyroid treatment. Pretibial myxedema developed one-year post-thyroidectomy and was managed with systemic glucocorticoids. She later received iodine-131 therapy, which led to hypothyroidism, and started to admit thyroid hormone replacement. The thyroid function test revealed normal TSH levels and increased TRAbs. Histopathology of skin lesions showed mucopolysaccharide deposition and increased collagen confirming myxedema. This case highlights the rare elephantiasis form of pretibial myxedema and underscores the importance of recognizing characteristic skin lesions in patients with hypothyroidism.

Concurrent pretibial myxedema and thyroid eye disease following mRNA COVID-19 vaccine in a patient with history of Graves’ disease

A 70-year-old female had a history of thyroid surgery for benign nodules and Graves’ disease. Following mRNA COVID-19 vaccination, she presented Graves’ orbitopathy and pretibial myxedema. Symptoms of thyroid eye disease and thyroid dermopathy improved after 500-mg methylprednisolone infusions.

SAT474 A Case Report Of Moyamoya Disease Associated With Uncontrolled Graves' Disease

Abstract Disclosure: Z. Tan: None. E. Briggie: None. M. Correia: None. Background: Moyamoya disease is an uncommon cerebrovascular disease that is featured by narrowing of large intracranial arteries and the development of prominent small-vessel collaterals. The etiology of Moyamoya disease is unknown, but it can be associated with multiple conditions including atherosclerosis, sickle cell disease, and Protein S deficiency. It is rarely associated with uncontrolled Graves’ disease. Clinical Case: A 37-year-old female with a history of Graves’ disease and type 1 diabetes presented with sudden onset of slurred speech and right-sided weakness. A CTA of the head and neck showed a small hypodensity in the left basal ganglia without corresponding perfusion deficit and narrowed left internal carotid arteries without focal stenosis. In addition, a brain MRI showed patchy infarcts in the left middle cerebral artery territory. A cervical and cerebral angiogram showed multiple areas of stenosis which was concerning for Moyamoya disease. She ultimately underwent balloon angioplasty of the left internal carotid artery with improvement in perfusion. During the workup for secondary causes of Moyamoya disease, her TSH was < 0.01 µIU/mL (0.270-4.20 µIU/mL), with elevated T4 at 3.84 ng/dl (0.80-1.80 ng/dl) and elevated TSI at 15.5 IU/L (< 0.54 IU/L). Importantly, she was diagnosed with Graves’ disease 2 years before admission, and this condition has never been well controlled due to poor compliance with methimazole. A TSH measured 5 months before admission was also undetectable with elevated T4 at 2.8 ng/dl. Her other workups for Moyamoya disease were negative including HIV antigen/antibody, syphilis IgG antibody, Lyme disease IgG & IgM antibodies, hepatitis panel antibodies, ANA, ANCA, free protein S, dsDNA antibody, factor 5 Leiden mutation, vascular endothelial growth factor-D and urine drug screening test. She started methimazole 20 mg daily and was discharged to acute rehabilitation. After rehabilitation, her Graves’ disease is slowly improving with most recent TSH < 0.008 µIU/mL and free T4 at 2.39 ng/dl. She is almost back to her baseline with significant improvement in speech and strength. Conclusion: Uncontrolled Graves’ disease should be considered in the differential diagnosis of Moyamoya disease in young subjects who present with stroke-like symptoms. Reference: Ischemic Stroke and Intraventricular Hemorrhage in Moyamoya Syndrome Associated With Graves' Disease: A Case Report. Neurologist 2022 Presentation Date: Saturday, June 17, 2023

Propylthiouracil induced ANCA-positive vasculitis in a patient with Graves’ disease; a case report

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis is rare, but it can be triggered by chemicals, infections, and drugs. Patients who use anti-thyroid drugs are prone to involve with ANCA-associated vasculitis. Perinuclear ANCA (p-ANCA) is almost always positive in these patients. Patients have various presentations and symptoms such as (arthritis, edema) and this disorder usually resolves with discontinuation of the drug, however, some patients require high-dose steroids, immunosuppressive or plasmapheresis. A 38-year-old woman with a history of Graves’ disease was on long-term treatment with propylthiouracil (PTU), presented with severe bone pain, arthritis and edema in both feet. The patient’s manifestations were resolved with discontinuation of PTU, iodine therapy, and corticosteroid administration.

P71: Use of Veno-Arterial Extracorporeal Membrane Oxygenation and Impella for Cardiogenic Shock due to Cocaine Abuse

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and Impella left ventricular assist device individually offer cardiovascular support for cardiogenic shock patients. Each modality has its own benefits and downfalls. We present a case in which a patient developed cocaine-induced coronary vasoconstriction resulting in cardiogenic shock with rapid systemic decompensation. We employed VA-ECMO and subsequent Impella to recover the patient. Methods: A 26-year-old male with a history of Graves’ Disease and chronic cocaine abuse presented to the ED with chest pain following cocaine ingestion. EKG showed sinus tachycardia and ST-elevations throughout, suspicious of coronary vasospasm. Labs showed an acute kidney injury as well as shock liver. Bedside echocardiogram (ECHO) revealed a severely depressed left ventricular ejection fraction (LVEF) of <10%. He was hemodynamically unstable for coronary catheterization and was emergently cannulated for VA-ECMO via the right femoral artery and left femoral vein. After we gained stability and slowly weaned the inotropic support. A follow-up ECHO revealed a dilated left ventricle and biventricular failure. With better hemodynamics, we did a catheterization showing coronary vasoconstriction, “clamping down” of distal vessels. (Figure 1) Due to the left ventricular dilation and its poor contractility, we decided to place an Impella. Results: The patient was supported on VA ECMO for 4 days, at which his LVEF recovered to 30-35%. The Impella device remained for an additional 3 days as his labs and hemodynamics improved. His LVEF at Impella removal was 40%. The patient was discharged in 14 days with a normal LVEF. Conclusion: One of the major downfalls of VA-ECMO is the lack of left ventricular unloading resulting in increased afterload and hindering recovery. An Impella can be used to help vent the left ventricle. This combination has been shown in several studies to improve outcomes in patients with acute coronary syndrome. The technique was employed with successful cardiac recovery in a patient who developed cardiogenic shock from coronary vasospasm from cocaine use.Figure 1. Coronary angiography showing coronary vasoconstriction due to cocaine use

Abstract #1407671: Thyroid Eye Disease Following COVID-19 Infection in a Patient with a History of Graves' Disease

Autoimmune and inflammatory thyroid diseases have been reported following SARS-CoV-2 infection or vaccination, but thyroid eye disease (TED) post-COVID-19 infection is less common. We describe a case of TED following SAR-CoV-2 infection in a patient with a history of Graves’ disease. A 59-year-old female with history of Graves' disease status post radioiodine ablation therapy in 2002. She developed post-ablative hypothyroidism which has been stable on levothyroxine 88 mcg daily. In January 2021, the patient's husband and daughter were diagnosed with COVID-19 infection. A few days later, the patient developed an upper respiratory tract infection associated with loss of sense of smell and taste consistent with COVID-19 infection. Three days later, she developed bilateral watery eyes which progressed to eye redness, eyelid fullness, retraction, and pain with eye movement over 1-month duration. Her eye examination was significant for severe periocular soft tissue swelling, lagophthalmos and bilateral exophthalmos. The laboratory workup was consistent with normal TSH 0.388 mIU/L (0.358-3.740 mIU/L) and positive TSI 1.01 (0.0-0.55). The patient was referred to an Ophthalmologist for evaluation of TED. He noted bilateral exophthalmos, no restrictive ocular dysmotility or compressive optic neuropathy (clinical activity score 4/7 points). CT scan of orbit showed findings compatible with thyroid orbitopathy. Based on clinical activity score of 4, treatment with Teprotumumab was recommended pending insurance approval. Many cases of new-onset Graves’ hyperthyroidism have been reported after COVID-19, with only a few associated with TED. Our patient has been in remission for 20 years before she developed COVID-19 infection with occurence of TED.This suggests that COVID-19 infection may have played a role. SARS-CoV-2 may act through several mechanisms, including breakdown of central and peripheral tolerance, molecular mimicry between viral and self-antigens, stimulation of inflammasome with release of type I interferon. In our patient, treatment with Teprotumumab was indicated due to Graves’ orbitopathy clinical activity score greater than or equal to 3. In conclusion, it is very uncommon for TED to present after COVID-19 infection. Our case reinforces the speculative hypothesis that SARS-CoV-2 virus could have triggered an autoimmune response against eye antigens. There is a need for increased awareness about the link between COVID-19 and autoimmunity to help better define the management of patients.

Abstract #1397146: Recurrent Thyrotoxicosis in a Woman with a History of Graves - Basedow Disease

Although the most common cause of thyrotoxicosis is Graves - Basedow disease (GBD), the determination of the cause of thyrotoxicosis is important for establishing appropriate management. We present the case of a woman with suspected surreptitious ingestion of thyroid hormones or factitious thyrotoxicosis. A 42-year-old female patient she was diagnosed with hyperthyroidism due to GBD at the age of 14. At age 17 she received RAI (10 mCi), developed hypothyroidism and started levothyroxine (L-T4). At age 38 she presented again with hyperthyroidism: TSH: < 0.004 uIU/mL (VN: 0.4-4) and FT4: 3.19 ng/dl (0.8-1.9). She was suspended L-T4 and started antithyroid drugs (thiamazole). Due to persistence of hyperthyroidism despite 40 mg/d of thiamazole. She was hospitalized for study; thyroid ultrasound showed an atrophic thyroid and thyroid scintigraphy with technetium-99m reported absence of uptake in the thyroid bed, Ab-TPO and Ab-Tg were negative, Thyroglobulin: <0.2 ng/ml (1.6-59.9). After discontinuation of thiamazole and without any other medication, thyroid hormones (FT4 and FT3) normalized within two weeks, factitious thyrotoxicosis was suspected, and she was discharged without medication. At 42 years of age, she returned due to hyperthyroidism with TSH: 0.004uIU/mL, FT4: 2.59 ng/dl, and FT3: 5.05 pg/ml despite having restarted thiamazole in her place of origin; she denied taking thyroid hormone or nutritional supplements. On examination: HR: 105 bpm, mild distal tremor and non-palpable thyroid. The results of the thyroid, thyroid scintigraphy, Ab-TPO, Ab-Tg and levels of Thyroglobulin were similar to the previous ones. Transvaginal ultrasonography and a whole-body scan with RAI ruled out ectopic hyperthyroidism; the FT3/FT4 ratio was always less than 4.4, suggesting factitious thyrotoxicosis. Antithyroid and beta-blockers were suspended, control at 48 hours showed: FT4: 1.77ng/dl (0.8-1.9), FT3: 3.4pg/ml (1.8-4.2) and 25 days post-discharge: TSH: 7.72 ng/dl, FT4: 1.48 ng/dl and FT3: 2.09 pg/ml. The psychiatric evaluation did not show any alteration. The patient was asymptomatic and returned to her place of origin. Cholestyramine was not accepted by the patient. Factitious thyrotoxicosis is difficult to identify, especially when dealing with a patient with a history of GBD. The diagnosis of factitious thyrotoxicosis is based upon the absence of goiter, suppressed serum Tg level, decreased radioactive iodine (RAI) uptake, and excellent response after cholestyramine treatment in cases in which this entity is suspected.

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.

Personal Reflections on the History of Graves' Disease

Clinical ThyroidologyVol. 35, No. 3 ATA Centennial Anniversary SeriesPersonal Reflections on the History of Graves' DiseaseTerry F. Davies and Dawn M. ElfenbeinTerry F. Davies Division of Endocrinology, Diabetes and Bone Diseases; Icahn School of Medicine at Mount Sinai, New York, New York, U.S.A.Search for more papers by this author and Dawn M. Elfenbein Division of Endocrine Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, U.S.A.Search for more papers by this authorPublished Online:14 Mar 2023https://doi.org/10.1089/ct.2023;35.86-92AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 35Issue 3Mar 2023 Information© Copyright 2023, Mary Ann Liebert, Inc.To cite this article:Terry F. Davies and Dawn M. Elfenbein.Personal Reflections on the History of Graves' Disease.Clinical Thyroidology.Mar 2023.86-92.http://doi.org/10.1089/ct.2023;35.86-92Published in Volume: 35 Issue 3: March 14, 2023PDF download

ATA Centennial Fireside Chat Expert Review Series: Personal Reflections on the History of Graves' Disease Treatment

This fireside chat is a part of the ATA's Centennial Series celebrating 100 years of the ATA. Drs. Dawn Elfenbein and Terry Davies discuss the evolution in our understanding and treatment of Graves' disease. They discuss how in the 19th century it was difficult to understand why some people with goiters could possibly be short of anything when others seemed to have gained some function. This led to surgeries being performed to remove the goiters, but then patients who underwent surgery suffered from tetany and myxedema, leading to the later discovery of the thyroid hormones and even later the role of the parathyroids. They discuss historic physicians and surgeons such as Drs. Victor Horsley, Theodore Kocher, and George Murray, who treated myxedema with thyroid transplants and thyroid extract, and the Clinical Society of London Report on Myxedema in 1888 that changed the whole concept of thyroidology by finally confirming thyroid deficiency as the cause of myxedema that in turn led to implicating the thyroid as also being involved in Graves' disease. Be sure to checkout Dr. Davies and Elfenbein's continued conversation in Supplementary Video SV1. No competing financial interests exist. Runtime of video: 22 mins

DESENSITIZATION TO PROPYLTHIOURACIL WITH SUBSEQUENT LONG-TERM THERAPY TOLERANCE IN A PREGNANT PATIENT

<h3>Introduction</h3> Thionamides are first line treatment for hyperthyroidism due to Graves' disease in pregnancy. Propylthiouracil (PTU) is preferred to methimazole in the first trimester, given risk of significant teratogenic effects with methimazole. Hypersensitivity reactions such as angioedema and anaphylaxis to thionamides have been reported, and there is concern for cross-reactivity between methimazole and PTU. A lack of data exists regarding the safety of graded challenge or desensitization to thionamides during pregnancy. <h3>Case Description</h3> A 33-year-old female with history of Graves' disease and prior urticaria and angioedema with use of methimazole presented to allergy clinic while 9 weeks pregnant with symptoms of tachycardia, jitteriness, dyspnea, and weight loss. She was diagnosed with thyroid storm and endocrinology recommended PTU initiation. Given her previous reaction to methimazole with potential risk of cross-reactivity as well as her urgent need for treatment during pregnancy, an outpatient graded challenge was deferred and she was admitted to the intensive care unit for a 7-step desensitization to PTU. She tolerated this during her first trimester of pregnancy without adverse events and was able to be continued on outpatient PTU for the remainder of her pregnancy with subsequent delivery of a healthy baby. <h3>Discussion</h3> Currently, 2016 American Thyroid Association Guidelines for Hyperthyroidism recommend against using methimazole or PTU in those who have had a serious side effect from the other agent due to concern of cross-reactivity, although this is not well quantified. This case reinforces that desensitization to thionamides can be safely performed during pregnancy in the setting of prior reactions.

A case of thyroid sclerosing mucoepidermoid carcinoma with eosinophilia indicates interleukin-5 production in a man with a history of Graves’ disease

Thyroid sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is a rare tumor that typically affects women with Hashimoto’s thyroiditis. The present case was a man in his late 50s who was diagnosed with Graves’ disease at the age of 10 and was given antithyroid hormone for five years. The computed tomography scan revealed a nodular lesion in the right lobe, and the lesion was cytologically suspected as papillary carcinoma. No lymph node metastases or distant metastases were found. Before total thyroidectomy, high serum anti-thyroid peroxidase (TPO) and antithyroglobulin (TG) antibody titers, with no eosinophilia were detected. In a few small areas of the tumor center, small tumor cell foci with mild to moderate atypia, displaying mucous glandular cell and squamous cell differentiation, were found. The tumor was completely replaced by prominent sclerosing fibrosis, which was accompanied by tumor cell infiltration. The tumor had invaded the adjacent parenchyma and perithyroidal fatty tissue. In addition to lymphocytes and plasma cells, a large number of eosinophils were observed within the tumor. Immunohistochemically, tumor cells were strongly positive for p63, 34βE12, and TTF-1, but weakly for PAX8. Using fluorescence in situ hybridization (FISH), no MAML2 translocation was detected. Taken together with these findings, the present tumor was diagnosed as primary thyroid sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE). This case is the first to report thyroid SMECE associated with Graves’ disease. IL-5 immunostaining was performed to identify eosinophilia within the present tumor. As a result, the tumor cells were found to be positive for IL-5. The present tumor is also the first to indicate IL-5 production of SMECE.

RF23 | PSAT301 Plasmapheresis and Extracorporeal Membrane Oxygenation (ECMO) for Treatment of Thyroid Storm with Multiorgan Failure

Abstract Introduction Thyroid storm is a life-threatening condition with a high morbidity and mortality rate. It can lead to severe end organ damage including liver injury, which can preclude the use of thionamides. Therapeutic plasma exchange can be a lifesaving option for treatment of thyroid storm in such cases. Multiorgan failure can also necessitate the use of extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). Case Presentation A 34-year-old woman with a history of Graves’ disease, untreated for several years, presented to the emergency department with fatigue, palpitations, dyspnea, and edema which developed over 1 month. Labs showed suppressed thyroid stimulating hormone (TSH) with significantly elevated free T4 of 10.8 ng/dL (normal 0.89-1.76 ng/dL). She had evidence of atrial fibrillation and heart failure. She was started on treatment with propylthiouracil, propranolol, and hydrocortisone and then Lugol's iodine was added. However, she quickly deteriorated with worsening mentation, dyspnea, and hypotension. She progressed to multiorgan failure including significant liver injury likely due to ischemic hepatitis. Thus, thianomides could not be used any further. She was started on cholestyramine; hydrocortisone and Lugol's iodine were continued.An echocardiogram revealed global hypokinesis with a left ventricular ejection fraction of 20%. Beta blockers were discontinued due to hypotension. The cardiogenic shock worsened despite aggressive medical therapy requiring initiation of veno-arterial (V-A) ECMO. She also required CRRT due to renal failure.Plasmapheresis was initiated for treatment of thyroid storm and she received 4 treatments with normalization of free T4: 1.48 ng/dL and T3 levels: 3.4 ng/dL (normal 2.3-4.2 ng/dL). Her condition subsequently improved and she was decannulated from the ECMO device after 5 days. She was then able to receive definitive treatment with thyroidectomy 11 days following admission. The patient was discharged in improved condition after a 10-week hospital course. Discussion Thyroid storm is a rare complication of thyrotoxicosis with a mortality rate of 10-30%. Treatment classically involves inhibiting the synthesis, release, and peripheral conversion of thyroid hormone as well as supportive management. Major causes of mortality in thyroid storm, present in our patient, include cardiogenic shock, arrhythmia, and multiorgan failure. Cardiac and hepatic failure can preclude the use of beta blockers and thionamides, which may necessitate the use of extracorporeal treatments, such as plasmapheresis for clearance of high burden of circulating thyroid hormone; V-A ECMO and CRRT for end organ damage. These therapeutic measures were used in our patient and led to a favorable outcome. This case highlights the successful use of these extracorporeal treatments as a bridge to thyroidectomy when standard medical treatment is contraindicated or unsuccessful. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 12:42 p.m. - 12:47 p.m.

Minimal change disease associated with Graves’ disease and methimazole use

Introduction. Graves' disease causes kidney injury through multiple mechanisms, including the treatment for this condition. Nephrotic syndrome due to minimal change disease (MCD) is an unusual form of such kidney injury; the association between methimazole use and MCD is also rare.&#x0D; Case presentation. 36-year-old woman with a history of Graves' disease in use of methimazole for several months, who presented with edematous syndrome due to nephrotic syndrome associated with a KDIGO stage 3 acute kidney injury. Thionamide-induced hypothyroidism and the need of thyroid hormone replacement therapy was evidenced at the time of consultation. Based on a renal biopsy, the patient was diagnosed with MCD. Her condition worsened as she experienced oliguria and hypervolemia, and renal replacement therapy with hemodialysis was temporarily required. Methimazole administration was suspended, and treatment consisting of prednisolone administration and levothyroxine supplementation was started, achieving hemodialysis suspension, gradual improvement of proteinuria until remission and full and maintained recovery of renal clearance. Radioiodine therapy was implemented as definitive treatment for Graves' disease, obtaining a successful outcome.&#x0D; Conclusions. Graves' disease and methimazole use are possible causes of minimal change disease. Systemic corticosteroid therapy is a possible management. However, further basic, clinical and epidemiological research on this subject is required.