bluuebunny/crossref_metadata_2025 huggingface dataset:
5125 Severe Gestational Thyrotoxicosis Leading to Unwarranted Treatment
Authors: Bell C , Barbour L A
Published: October 2024

Disclosure: C. Bell: None. L.A. Barbour: None.

Introduction: Gestational transient thyrotoxicosis (GTT) is the most common cause of thyrotoxicosis in pregnancy yet is often confused with Graves’. Although usually mild, we present a severe case leading to the unsupported use of anti-thyroid drugs (ATDs), which could have resulted in fetal hypothyroidism if continued. Case: A 30-year-old female G1P0 at 10 wks with a single gestation presented with 4 wks of vomiting, palpitations, and weight loss. She had no history of thyroid disease. She was diaphoretic and ill-appearing and had a non-tender, smooth normal-sized thyroid, a stare without exophthalmos, and a fine tremor. TSH was < 0.01, FT4 5.57 ng/dL (0.89-1.76), and TT3 201 ng/dL (60-181). TPO Ab 51 (< 60). TRAb, TSI Ab, and TgAb were negative. β-hCG level was 334,106 mIU/mL. She was diagnosed with GTT and briefly hospitalized for dehydration but was re-hospitalized 2 wks later with worsening symptoms and 25 lb weight loss. Unexpectedly, her FT4 and TT3 rose to 6.24 ng/dL and 339, respectively. A thyroid ultrasound showed mildly increased vascularity. PTU was started for seronegative Graves’ at 50 mg tid with metoprolol. After 3 days, her FT4 improved to 3.59 ng/dL and TT3 was 176. Further consultation recommended stopping PTU. She was sent home with metoprolol. Her symptoms and FT4 levels improved. FT4 was normal and hCG levels dropped to 54,821 by 18 wks. Discussion: GTT is caused by a transient elevation in T4 due to direct hCG stimulation of the TSH receptor. It is more common with multiple or molar gestations and hyperemesis gravidarum, also mediated by hCG. It typically results in mild thyrotoxicosis, highlighting the uniqueness of this case. Only a couple of case reports exist where GTT presented as severe thyrotoxicosis or thyroid storm and persisted this long. It is critical to distinguish GTT from Graves’ given their different outcomes and treatment. GTT is commonly misdiagnosed as Graves’ as both result in thyrotoxic labs and symptoms and can present in 1st trimester. GTT typically presents at 8-10 wks and lasts until 14-16 wks when hCG levels fall, but Graves’ may also improve by 2nd trimester due to the immune suppression of pregnancy. It is also possible for both to co-exist. hCG levels >100,000 are associated with GTT but due to the variable sialylation of hCG, which changes its affinity to the TSH receptor and half-life, they are unreliable diagnostically. Key clues supporting GTT include no goiter, exophthalmos, or symptoms pre-pregnancy, negative TRAb and TSI, and, notably, a lower T3/T4 ratio compared to Graves’, as seen in this case. To conclude, GTT is often mistaken for Graves’ but inappropriate use of ATDs can result in fetal hypothyroidism and does not improve outcomes. Although the severity of our case is unusual, accurate distinction from Graves’ by endocrinologists is crucial to ensure optimal maternal-fetal outcomes.

Presentation: 6/1/2024
7443 Severe Hypothyroidism and Adrenal Insufficiency in a 27-Year-Old Male with Klippel-Feil Syndrome: A Case Report
Authors: Almardini Shaza , Haddadin Fadi , Aoun Laurence , Saliba Fares , Zaidan Julie
Published: October 2024

Disclosure: S. Almardini: None. F. Haddadin: None. L. Aoun: None. F. Saliba: None. J. Zaidan: None.

Background: Klippel-Feil syndrome (KFS) is a rare congenital disorder characterized by improper segmentation of the cervical vertebrae. The classical clinical triad consists of short neck, low posterior hairline, and limited neck mobility. It is uncommonly associated with endocrine abnormalities. We present a rare case of KFS with severe primary hypothyroidism. Case Presentation: A 27-year-old male with KFS presented for evaluation of profound fatigue and lack of energy. His vital signs revealed a heart rate of 50 and a borderline low blood pressure. On physical exam patient was noted to be lethargic and icteric, thyroid exam was limited due to patient short neck. Labs were consistent with severe hypothyroidism TSH of 825 mIU/L, total T4 <0.4 mcg/dL, low 8 AM cortisol of 4.3 mcg/dL, elevated LDL at 333 mg/dL, elevated liver enzymes AST 491 U/L, ALT 294 U/L, neutropenia with WBC 2.69 x10^3/uL 20% neutrophils and anemia Hb 12 g/dL. TPO and thyroglobulin antibodies were positive at 149.0 and 109.0 IU/mL respectively, 21 hydroxylase antibodies were negative. Thyroid Ultrasound showed small and diffusely heterogenous thyroid. Patient was started on Levothyroxine 125 mcg daily and hydrocortisone with improvement in his symptoms as well as normalization of his lipid panel, liver enzymes and neutropenia. The patient was continued on levothyroxine 125 mcg, hydrocortisone was tapered and repeat cortisol levels were normal. Discussion: This case demonstrates an unusual association between KFS and hypothyroidism secondary to Hashimoto thyroiditis, likely representing an incidental finding rather than a causative relationship. The cervical spinal abnormalities and short neck characteristic of KFS could potentially lead to compression of neurological and vascular structures in the neck. However, this is unlikely to fully explain our patient's hypothyroidism. There are few published case reports of KFS with endocrine disorders in the literature that describe incidental findings like autoimmune thyroiditis and hypoparathyroidism, but there is no known biological mechanism linking KFS and endocrine dysfunction. Moreover, there is no evidence in either our patient's case or in existing literature to suggest a higher occurrence of autoimmune disorders like Hashimoto in such individuals. Conclusion: we present a novel case of KFS found incidentally with primary hypothyroidism. While these endocrine disorders could compound the growth delay and developmental issues typically seen in KFS, they do not appear to be causally related. This case highlights the need to monitor endocrine function in KFS patients and serves as a reminder that common conditions may co-occur simply by chance.

Presentation: 6/3/2024
7527 Subacute Thyroiditis in First Trimester of Pregnancy: Rare Cause of Thyrotoxicosis
Authors: Wilcher K , Gupta A
Published: October 2024

Disclosure: K. Wilcher: None. A. Gupta: None.

Background: Subacute thyroiditis (SAT) is extremely rare in pregnancy with only 8 prior cases reported in the literature. SAT can result in maternal and fetal complications. In this case report, we describe a case of subacute thyroiditis presenting in the first trimester of pregnancy. Case Presentation: A 38-year-old female with past medical history of stillbirth presented with thyrotoxicosis in gestational week 10 of her pregnancy. The patient has a history of stillbirth in gestational week 38 of her first pregnancy requiring cesarean section one year prior to presentation. She was in the process of getting in vitro fertilization (IVF) and had an egg retrieval. During the process, she started on thyroxine 50 mcg daily for blood thyroid-stimulating hormone (TSH) 3.77 mcIU/mL. She became pregnant without the help of IVF and stopped thyroxine. One month later, labs showed low TSH 0.022 mcIU/mL (reference range: 0.4-4.5 mcIU/mL) and high blood free thyroxine (FT4) 1.87 ng/dL (reference range: 0.7-1.8 ng/dL). Repeat labs two weeks later showed low blood TSH 0.012 mcIU/mL, high FT4 2.08 ng/dL, and high blood free triiodothyronine (FT3) 5.2 pg/mL (reference range: 2.3-4.2 pg/mL). She was referred to endocrinology for evaluation. She reported mild intermittent right sided neck pain since diagnosis of pregnancy. She denied any history of viral infection, cough, or fever. She reported symptoms of severe nausea, mild constipation, and mild anxiety. She denied diarrhea, tremors, changes in voice, palpitations, or weight loss. Her family history is significant for hypothyroidism in her father. Physical exam demonstrated a non-tender, symmetric thyroid without enlargement or nodules. Ultrasound showed heterogenous thyroid with an ill-defined heterogenous area in the right lobe appearing pseudo-nodule, and increased vascularity. At this time, the patient was diagnosed with mild gestational hyperthyroidism with a plan to monitor thyroid hormone levels. Repeat labs two weeks later showed low blood TSH 0.005 mcIU/mL, high FT4 2.35 ng/dL, and high FT3 6.4 pg/mL. TSH-receptor antibodies, thyroid stimulating immunoglobulin, and thyroid peroxidase antibodies were normal on testing. In gestational week 16, labs showed normal TSH 2.76 mcIU/mL, low FT4 0.56 ng/dL, and low FT3 2.1 pg/mL. At that time, she started on levothyroxine 75 mcg daily and was diagnosed with subacute thyroiditis. Follow up labs in gestational weeks 18, 20, and 24 showed improvement in TSH and FT4 on thyroid hormone supplementation. Conclusion: This case report discusses the findings of SAT in first trimester pregnancy. Currently, she is in gestational week 28 and still requiring thyroid hormone supplementation. SAT in pregnancy is very rare. This case report significantly contributes to the literature and current knowledge of the prevalence, presentation, and disease process of subacute thyroiditis in first trimester pregnancy.

Presentation: 6/2/2024
6423 The Storm in a Healthy 26-year-old Hispanic Female
Authors: Reyes-Torres Paola M , Hernandez-Hernandez Marimar
Published: October 2024

Disclosure: P.M. Reyes-Torres: None. M. Hernandez-Hernandez: None.

Uncontrolled hyperthyroidism can cause thyrotoxicosis and lead to end-organ dysfunction known as thyroid storm. The incidence is .20 and .76 per 100,000 persons per year, with an incidence of 4.8–5.6 per 100,000 hospitalized patients. Of those hospitalized with thyrotoxicosis in the U.S., thyroid storm is diagnosed in 16%. Most commonly affects females, middle-aged patients, and Caucasians. Can be precipitated by acute illnesses, surgery, or non-compliance with medications. Symptoms are characterized by fever, cardiac and gastrointestinal dysfunction, and altered mentation along with impaired thyroid function tests.A 26-year-old Hispanic female presented to our ER complaining of palpitations, general malaise, dysphagia, and fevers after attending a social event 3 days before. Physical examination revealed a fever of 101F, restless patient with pressured speech, and diffusely enlarged non-tender thyroid without discrete nodules. Labs were remarkable for WBC: 12 000, urinalysis, b-HCG, and CXR were all negative. Burch-Wartofsky Point Scale: 55 and biochemical tests (TSH: 0.005 ml/UL, free T4 >5 ng/dL, Total T3: 8.5 ng/mL, Total T4: 28.87 uG/DL, Thyroglobulin 34.81 ng/mL) for which diagnosis of thyroid storm was made. She was transferred to the ICU and treatment was initiated with fluids, Propranolol 60 mg PO q4hrs, PTU 250 mg PO q4hrs, and Hydrocortisone 300 mg IV as loading dose then 100mg IV q8hrs. TSI and TRAb were ordered. Thyroid US remarkable for bulky thyroid gland with heterogeneous, increased vascularity, no obvious cystic/solid lesions seen. Repeated tests showed a decreasing trend of free T4: 4.71 ng/dL and Total T3: 2.42ng/dL for which PTU was discontinued and Methimazole 15 mg PO BID was started. Five days after treatment started, the patient continued symptom-free and was discharged with Propranolol 60 mg PO q6hrs and Methimazole 15 mg PO BID. TSI and TRAb samples were obtained but results were pending before discharge. Follow-up was scheduled in 2 weeks with routine labs but the patient was lost to follow-up.This case highlights the importance of early recognition and treatment of thyroid storm in Hispanics, undiagnosed patients given the presenting nonspecific, life-threatening symptoms. We conclude that our patient's cause of thyrotoxicosis was an undiagnosed case of Graves Disease and the storm was most likely triggered by an upper viral respiratory tract infection. This case could potentially help physicians identify hyperthyroidism in an earlier phase, reducing incidence, mortality, and hospitalizations of thyroid storm since a variety of mimics make the diagnosis challenging. Furthermore, we could contribute to updated statistical knowledge regarding the risk of patients with thyrotoxicosis developing thyroid storm which despite advancements in technology, are currently lacking.

Presentation: 6/1/2024
7046 Thyroid Storm After Thyroidectomy Without Underlying Hyperthyroidism
Authors: White-Cotsmire A J , Kodali B , McHenry C , Rahhal M N
Published: October 2024

Disclosure: A.J. White-Cotsmire: None. B. Kodali: None. C. McHenry: None. M. Rahhal: None.

Background: Thyroid storm is a feared complication of total thyroidectomy; however, this is a rare phenomenon seen primarily in patients with undiagnosed or poorly controlled thyrotoxicosis from Graves’ disease. Preoperative treatment of patients with hyperthyroidism with beta-adrenergic blockers and anti-thyroid medication to ensure that patients are euthyroid prior to thyroidectomy have largely eliminated this risk of thyroid storm. (1) We report a case of thyroid storm caused by release of preformed thyroid hormone, following extensive manipulation and resection of a large retrosternal nontoxic multinodular goiter. To our knowledge, this has not yet been previously described. Clinical Case: A 57yo female underwent a total thyroidectomy with resection of a large benign multinodular goiter with retrosternal extension, which was causing compressive symptoms. She had a nodular goiter for 7 years that was increasing in size. Fine needle aspiration 2 years prior to surgery demonstrated colloid and adenomatoid nodules with Hurthle cell changes. She had no history of hypo- or hyperthyroidism. TSH prior to surgery was 0.576µIU/ml (normal = 0.450-5.330µIU/ml). Extensive manipulation was required to deliver the goiter from beneath the manubrium. Pathology from her thyroid revealed a multinodular goiter without evidence of malignancy. Post-operative course was uncomplicated, and after an overnight stay, the patient was discharged home with 150mcg (1.5mcg/kg) levothyroxine daily. She presented to the emergency department 4 days later and was admitted to the intensive care unit with diffuse abdominal pain, nausea, vomiting, and myalgias, and she was diagnosed with atrial fibrillation with rapid ventricular response. TSH on admission was 0.020 µIU/ml, thyroglobulin levels were >2,250.0ng/mL (n=0.8 – 48.0 ng/mL), thyroglobulin antibodies were negative. Her levothyroxine was stopped, her heart rate was controlled with metoprolol, and she was started on oral anticoagulation with rivaroxaban. She was discharged after a 7-day hospital stay. At 3 weeks follow-up her TSH was 35.67µIU/ml and her thyroglobulin levels were 23.9ng/mL. Her symptoms had resolved, and levothyroxine was resumed at a lower dose of 137mcg daily. Six weeks later her TSH level was 7.785µIU/ml, and her thyroglobulin was 1.8ng/mL. Conclusion: To our knowledge, this is the first case of thyroid storm reported following thyroidectomy in a patient with nontoxic multinodular goiter in a clinically and biochemically euthyroid patient. Massive increase in thyroglobulin postoperatively and rapid resolution of symptoms suggest that the release of preformed thyroid hormone related to vigorous thyroid manipulation was likely the cause. Reference: (1) Christou N, Mathonnet M. Complications after total thyroidectomy. Journal of Visceral Surgery. 2013;150(4):249-256. doi:10.1016/j.jviscsurg.2013.04.003

Presentation: 6/1/2024
8238 Thyroidectomy for Thyroid Storm Complicated by Drug-Induced Hepatotoxicity and Thyrotoxic Cardiopulmonary Disease
Authors: John Tara A , Suarez Audry C , Genkil Jessica , Patil Shivaraj , Anastasopoulou Catherine
Published: October 2024

Disclosure: T.A. John: None. A.C. Suarez: None. J. Genkil: None. S. Patil: None. C. Anastasopoulou: None.

Case Presentation: A 59-year-old female with hypertension and type 2 diabetes presented with palpitations, and several months of hyperthyroid symptoms, lower extremity swelling, and dyspnea on exertion. On presentation, patient was diaphoretic, tachycardic, volume overloaded and had symmetric swelling of the thyroid gland. Lab results revealed FT4 3.28 ng/dL, total T3 384.59 ng/dL, TSH < 0.01 µIU/mland elevated TSI. Electrocardiogram showed sinus tachycardia. Chest radiography showed pulmonary edema. Echocardiography showed a reduced ejection fraction of 35%, dilation of right ventricle, severe mitral and tricuspid regurgitation, and severely elevated pulmonary artery systolic pressure (55-60 mm Hg). Thyroid ultrasound revealed enlarged, heterogeneous thyroid gland with normal vascularity. The diagnosis of thyroid storm due to Graves' disease was made with a score of 50 on the Burch-Wartofsky Point Scale. Patient was started on propylthiouracil (PTU), metoprolol tartrate and furosemide. Corticosteroid therapy was not utilized due to the risk of worsening heart failure from sodium retention. After two days of PTU, patient developed drug induced liver injury (DILI). Patient was then transitioned to methimazole which was also discontinued thereafter due to progression of DILI. She was started on potassium iodide to suppress thyroid hormone production, and N-Acetyl cysteine (NAC) for DILI. Due to persistent thyrotoxicosis, the patient underwent a total thyroidectomy on hospital day 13 and was started on levothyroxine for post-surgical hypothyroidism. Liver function returned to normal on day 16. A surveillance echocardiogram obtained 3 months later showed recovered biventricular function (ejection fraction 55-60%), mild mitral and tricuspid regurgitation and normal pulmonary pressures. Educational value: Thyroid storm is an uncommon, life-threatening emergency. Thioamides remain the cornerstone of treatment, but rarely, they can result in adverse events such as hepatotoxicity. When thioamides are contraindicated, other agents (e.g., iodine, lithium, potassium perchlorate, cholestyramine, glucocorticoids) can be utilized; however, refractory cases might require total thyroidectomy as definitive treatments. Our patient had marked recovery of cardiac function and resolution of pulmonary hypertension and DILI after timely surgical intervention. Multidisciplinary care is pivotal for the successful management of thyroid storm.

Presentation: 6/3/2024
12598 Tides of the Thyroid: Myxedema Ascites Unveiled
Authors: O’Neal Eric , Duong Diana , Caplan Michael , Bird Kimberly
Published: October 2024

Disclosure: E. O'Neal: None. D. Duong: None. M. Caplan: None. K. Bird: None.

Background: Primary hypothyroidism is a common clinical condition, complicated by ascites in less than 4% of cases. Myxedema ascites, caused by hypothyroidism, is also a rare cause of ascites in less than 1% of new onsets. Clinical Case: We present a 78-year-old female who initially presented to the hospital for abdominal swelling. CT of the abdomen/pelvis revealed a large amount of ascites in the abdomen and pelvis, along with bilateral pleural effusions. Labs were remarkable for a TSH level of 149 uIU/mL and a free T4 level of 0.41 ng/dL. A review of the patient’s chart showed a period of hyperthyroidism in 2022, and the patient had been placed on methimazole 10 mg by mouth daily. After several months, the patient transitioned to hypothyroidism. Methimazole was discontinued and levothyroxine was initiated. Improper medication reconciliation later occurred when she was admitted into a nursing home, causing the patient to be on methimazole and levothyroxine concomitantly in the outpatient setting. During the patient’s hospitalization, three liters of ascitic fluid were removed via ultrasound-guided paracentesis. The etiology of hypothyroidism-induced ascites includes multiple theories. This unique phenomenon can be explained by the following: increasing capillary permeability due to low levels of circulating thyroid hormone, formation of hyaluronic acid-albumin complexes, low nitric oxide, increased Vascular Endothelial Growth Factor, and diminished free water clearance due to excess Antidiuretic Hormone. When capillary permeability is elevated, this allows for protein extravasation. Lymphatic homeostasis becomes compromised, and this leads to the development of ascites. Investigations for this condition include an abdominal paracentesis and ascitic fluid analysis, which demonstrates an elevated protein count and lymphocyte count, with variability in leukocyte count and serum-ascites albumin gradient. Treatment for this reversible condition requires adequate thyroid replacement therapy. Our patient’s levothyroxine was increased to 100 mcg by mouth daily, and the patient demonstrated an appropriate response with monitoring of TSH. Discussion: Although ascites is typically thought to be of hepatic or cardiac origin, it is important to remember to rule out other potential causes such as thyroid disease. Reference: [1] Khalid, S., Asad-Ur-Rahman F., Abbass, A., Gordon, D., Abusaada, K. Myxedema Ascites: A Rare Presentation of Uncontrolled Hypothyroidism. Cureus 2016 Dec;8(12); e912.

Presentation: 6/2/2024
7962 Transformation of Poorly Differentiated Papillary Thyroid Carcinoma to Anaplastic Thyroid Carcinoma, an Atypical Course!
Authors: Altaweel Tamara , Makadsi Sarah , Hussein Marwah , Samantray Julie
Published: October 2024

Disclosure: T. Altaweel: None. S. Makadsi: None. M. Hussein: None. J. Samantray: None.

Introduction: Anaplastic thyroid cancers are undifferentiated, rare and aggressive. The transformation of papillary thyroid cancer to anaplastic thyroid cancer is documented in literature, however, rare. In this report, we present a case of Anaplastic thyroid carcinoma likely arising from a co-existing poorly differentiated Papillary carcinoma. Case Presentation: A 74-year-old male with past medical history of tobacco smoking who presented with the onset of voice hoarseness for 6 months. He has also noticed a left neck mass that is in the mid supraclavicular region. A Neck CT neck was performed at the time of presentation and was significant for a 4.6x3.4x5.9 cm left thyroid mass with displacement of the trachea. FNA biopsy showed papillary carcinoma with focal features of Tall Cell Variant. Poorly differentiated components with fragments of stroma and muscle were seen and suggested invasion. These findings raised the possibility of anaplastic thyroid carcinoma in the setting of papillary carcinoma and poorly differentiated carcinoma. BRAF V600E pathogenic variant mutation along with TERT mutation were found. Patient underwent direct laryngoscopy, bronchoscopy with biopsies, and tracheostomy with surgical pathology confirming papillary thyroid cancer with muscles invasion. Combination dabrafenib and trametinib were started. No surgical resection of thyroid tissue was planned. A follow up CT showed a significant decrease in the low-density soft tissue involving the medial thyroid gland bilaterally, consistent with interim positive response to therapy. Three months later, CT neck showed near complete resolution of low-density soft tissue involving the medial thyroid and parathyroid glands and subglottic trachea consistent with further interim positive response to therapy. Six months post initiation of therapy, CT Neck showed focal low density in the mid and inferior right thyroid gland which may represent residual and/or recurrent thyroid carcinoma. That density was further demonstrated on a repeat CT neck as a 1.8 cm hypodense nodule in the inferior right thyroid gland and concerning for recurrent thyroid tumor with possible infiltration of the trachea. Conclusion: ATC prognosis is affected by many factors such as metastasis, age, treatment strategies, socioeconomic status and the presence of BRAF V600E and TERT mutations. Diagnosis can be challenging. Our patient presented months after his symptoms started and this is an atypical course of Anaplastic Thyroid Carcinoma as it usually progresses aggressively and rapidly. Given the pathology reports and the more slow presentation of this patient’s carcinoma, it can be suggested that this is a case of papillary carcinoma with a later transformation to ATC. In these cases, surgical resection

Presentation: 6/2/2024
7617 Two Cases of Severe Beta-hCG-Mediated Hyperthyroidism with Gestational Trophoblastic Disease
Authors: Morvant A , Mashayekhi M
Published: October 2024

Disclosure: A. Morvant: None. M. Mashayekhi: None.

Introduction: Hyperthyroidism is most commonly caused by Graves’ disease and toxic nodules and affects 2.5% of the world’s population. Hyperthyroidism due to elevations in beta-hCG (b-hCG), which has thyroid-stimulating activity due to homology with TSH, is a rare process that requires high clinical suspicion. We present two cases of hyperthyroidism caused by severely elevated b-hCG due to gestational trophoblastic disease (GTD), with rapid resolution of hyperthyroidism after treatment of the underlying conditions. Clinical Cases Case 1: A 35-year-old at 28-weeks gestation presented with dyspnea, palpitations, and 6-pound weight loss over the prior month. Labs revealed b-hCG 5.2 million (0-5 mIU/mL), TSH <0.015 (0.35-3.6 mcU/mL), and free T4 2.42 (0.7-1.37 ng/dL). Imaging revealed extensive pulmonary lesions concerning for metastatic disease and a 2.4 cm ovarian mass. Due to worsening respiratory distress and the need to start chemotherapy urgently, she underwent Cesarean section to deliver the viable infant and take out the ovarian mass. Pathology confirmed choriocarcinoma. Methimazole was started post-operatively, and she started chemotherapy. Labs after cycle one of chemotherapy showed b-hCG 1.3 million, TSH <0.015, and free T4 1.46. The methimazole dose was decreased and ultimately stopped as free T4 levels decreased with subsequent chemotherapy cycles. After three cycles, labs showed b-hCG 4,652, TSH 1.55, and free T4 0.68. She was discharged without thyroid-targeting therapy. Case 2: A 33-year-old woman at 12-weeks gestation presented with nausea, vomiting, and 10-pound weight loss over 1 month. Labs showed TSH <0.015, free T4 2.39, and total T3 351 (58-160 ng/dL), which were thought to be due to hyperemesis gravidarum. Two months later she presented with vaginal bleeding and imaging showed an enlarged placenta with a moth-eaten appearance and theca lutein cysts concerning for partial molar pregnancy. Beta-hCG level was 3.3 million, TSH <0.015, free T4 1.76, and total T3 289. She underwent dilation and evacuation and pathology confirmed partial hydatidiform mole. Beta-hCG level decreased to 1.8 million and free T4 normalized after surgery, with b-hCG 3,300, normal TSH, and normal total T3 one month later. Conclusion: These cases highlight the importance of considering possible GTD when evaluating a patient with hyperthyroidism, particularly in women of childbearing age and cases of early pregnancy when the degree of hyperthyroidism seems out of proportion to that expected. Clinicians should consider checking a b-hCG level in consultation with an obstetrician when indicated. Treatment is aimed at the GTD and can yield rapid resolution of hyperthyroidism. References: Pereira JV, Lim T. Hyperthyroidism in gestational trophoblastic disease - a literature review. Thyroid Res. 2021 Jan 14;14(1):1. doi: 10.1186/s13044-021-00092-3. PMID: 33446242; PMCID: PMC7807451.

Presentation: 6/2/2024
8062 Uncommon Presentation Of Multiple Myeloma As A Rapidly Growing Thyroid Goiter Initially Thought To Be Hashimoto's Thyroiditis
Authors: Singh Shah Mahabir , Humayon Salman , Paul Sanu Kevin , Peñaherrera Carlos
Published: October 2024

Disclosure: M.S. Shah: None. S. Humayon: None. K.P. Sanu: None. C. Peñaherrera: None.

We present a unique case of an 85-year-old female with rapidly growing anterior neck swelling and subclinical hyperthyroidism, initially suggestive of Hashimoto's thyroiditis. The goiter initially responded well to steroids but rebounded back in size despite two courses of prednisone. This prompted further diagnostic workup which revealed unexpected findings, ultimately leading to the diagnosis of multiple myeloma involving the thyroid parenchyma and lymph nodes. The patient had no history of thyroid disorders or recent upper respiratory tract infections. She exhibited sudden neck swelling, mild subclinical hyperthyroidism, and positive TPO antibodies. Initial fine needle aspiration suggested lymphoid tissue with Hurthle cell differentiation, raising suspicion of Hashimoto's thyroiditis. Flow cytometry supported this diagnosis, but the potential for a Hurthle cell neoplasm persisted. Prednisone temporarily reduced thyroid size, but disease recurrence necessitated surgical excisional and incisional biopsies. Subsequent biopsies revealed plasma cell neoplasms consistent with multiple myeloma. The pathologic report confirmed MYC rearrangement, indicative of multiple myeloma involvement in lymph nodes and thyroid tissue. Protein electrophoresis revealed two restricted bands migrating in the gamma globin region. The patient experienced subclinical hyperthyroidism that evolved into euthyroidism over a month. Incidental findings included non-invasive, low grade papillary urothelial carcinoma. Disease progression was evident in a follow-up PET/CT, prompting oncology consultation. The patient initiated Revlimid with chemotherapy. Levothyroxine was prescribed for postoperative hypothyroidism, with adjustments based on thyroid panel results. This case report illustrates the intricate diagnostic challenges posed by multiple myeloma masquerading as a thyroid disorder. The unexpected evolution of the disease, marked by MYC rearrangement and metastatic spread, emphasizes the need for heightened vigilance in managing such cases. Clinicians should consider alternative diagnoses when treatment efforts fail to provide adequate response. This will ensure timely and appropriate management in clinical practice. This report contributes valuable insights into the diagnostic complexities and multidisciplinary considerations for addressing similar presentations in endocrine and oncology settings.

Presentation: 6/1/2024
12452 Unraveling An Intriguing Clinical Sequence: Thyrotoxicosis Antecedent To Stiff Person Syndrome
Authors: Jain Ashali , Natasha Rayan Melanie
Published: October 2024

Disclosure: A. Jain: None. M.N. Rayan: None.

Title: Unraveling an Intriguing Clinical Sequence: Thyrotoxicosis Antecedent to Stiff Person Syndrome Background: Stiff Person Syndrome (SPS) is an autoimmune phenomenon resulting in the progressive rigidity of limbs and trunk muscles. It is associated with GAD-positive antibodies in the CSF and serum and is linked to Type 1 Diabetes, Celiac disease, and other autoimmune diseases. Clinical Case: A 34-year-old female with no past medical history was brought into the ED by family for paranoia, suicidal ideations, and visual and auditory hallucinations. She was found to be tachycardic and altered in the ED. Endocrinology was initially consulted for concerns of hyperthyroid pathology due to lab work showing a TSH of <0.008 uIU/mL and free T4 of 4 pg/mL. Thyroid ultrasound revealed heterogeneous, hypervascular thyroid tissue. Further investigation revealed TRAB 4.05 IU/L (n 0-0.9 IU/L) and TSI 3 IU/L (n < 0.577 IU/L). A diagnosis of Graves’ disease was made, and she was started on methimazole 20mg daily and metoprolol 25mg daily. Due to a lack of response to methimazole, other organic causes were investigated including psychiatric and neurological etiology. The patient's symptoms continued to worsen, with new tremors of the upper and lower extremities. Thyroid labs showed improvement, and hence thyrotoxicosis was not thought to be the underlying etiology of her encephalopathy. Neurology was consulted, and EEG and MRI Brain were performed which were unrevealing. Lumbar puncture revealed elevated oligoclonal bands and GAD-65 antibodies, suggesting autoinflammatory encephalitis. High-dose steroids were started, with no improvement. Due to the failure of steroids to treat her symptoms, she was given 5 days of plasmapheresis and a dose of rituximab. Slowly, the patient began to improve and could follow commands and communicate with staff. A formal diagnosis of SPS was made at this time. Upon seeing her in follow-up 1 month after discharge, her TRAB and TSI antibodies were negative, and she was able to be titrated off of methimazole. Conclusion: SPS is strongly associated with autoimmune diseases, with up to 30-40% having T1DM. The association between hyperthyroidism and SPS, however, is exceedingly rare and the etiology remains unclear.

Presentation: 6/1/2024
7695 Impact Of Day Of Admission On Outcomes Of Adrenal Insufficiency- A National Inpatient Sample Study
Authors: Karki Sunita , Neupane Binita , Neupane Shila , Bhandari Abhishek , Farooq Umer , Rajamani Krishnakumar
Published: October 2024

Disclosure: S. Karki: None. B. Neupane: None. S. Neupane: None. A. Bhandari: None. U. Farooq: None. K. Rajamani: None.

Introduction: Admission day (weekend vs. weekday) significantly influences hospital outcomes and mortality in various diseases, with evidence suggesting higher mortality rates associated with weekend admissions. However, the “weekend effect” on adrenal insufficiency remains underexplored in national inpatient samples. Objective of the study:To assess the impact of admission day on mortality rates, hospital stays, costs, and overall outcomes in adrenal insufficiency patients. Methods: A retrospective cohort study encompassing adult patients (age>18 years) was conducted using the National Inpatient Sample (NIS) data spanning from 2017 to 2020. The International Classification of Disease (ICD-10) was used to select codes for diseases and outcomes. STATA was employed for statistical analysis, using multivariate regression analysis to calculate adjusted odds ratios and account for potential confounding variables. Continuous variables were compared using the student t-test, while proportions were compared using the Fisher exact test. The primary outcome was mortality, with secondary outcomes encompassing length of stay (LOS), total hospitalization charges, acute coronary syndrome (ACS), septic shock, pulmonary edema, acute respiratory failure (ARF), mechanical ventilation, acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and cerebrovascular accidents (CVA). Results: A total of 150,005 patients diagnosed with adrenal insufficiency were included in the analysis. Patients with adrenal insufficiency were categorized into two groups based on the day of admission: weekend and weekday. Weekend admissions constituted 23.5% of the total cases of adrenal insufficiency, with 35,330 patients. Significant differences in outcomes were observed in septic shock (aOR=1.16, 7.24 % vs. 6.30 %, p=0.007), ARF (aOR=1.23, 11.82% vs. 9.87%, p<0.001), mechanical ventilation (aOR=1.35, 6.29% vs. 4.76%, p<0.001), ARDS (aOR=1.83, 0.57% vs. 0.33%, p=0.003), and AKI (aOR=1.15, 24.74% vs. 22.58%, p<0.001) in weekend vs weekday admissions. However, no significant differences were observed in mortality rates, mean length of hospital stay, total hospital costs, ACS, pulmonary edema, and CVA. Conclusion: Weekend admissions for adrenal insufficiency showed poorer outcomes which prompts further investigation into underlying factors. Insights gained might be helpful for strategic planning at state and national levels, aiding in outcome improvement.

Presentation: 6/1/2024
8072 Crosstalk Between E-Cadherin Loss And Estrogen Receptor Drives Tumorigenesis In Invasive Lobular Carcinoma
Authors: Ufondu Chinasa A , Musick Maggie , Joseph Sikora Matthew , Hanson Ostrander Julie
Published: October 2024

Disclosure: C.A. Ufondu: None. M. Musick: None. M.J. Sikora: None. J.H. Ostrander: None.

Estrogen receptor (ER) expression and E-cadherin (CDH1) loss are the two major molecular hallmarks of invasive lobular carcinoma (ILC) of the breast; however, it is unclear how ER signaling and E-cadherin loss crosstalk during ILC tumor formation. Furthermore, the risk of ILC is increased by estrogen-only hormone replacement treatment, but not that of the more frequent invasive ductal carcinoma (IDC), suggesting that ER may have a unique role in the initiation and progression of ILC. We hypothesize that E-cadherin loss accelerates estrogen-driven tumorigenesis by reprogramming ER DNA binding through the dysregulation of pathways and transcription factors linked to E-cadherin. To test the effect of E-cadherin loss during estrogen driven tumorigenesis, we established a CRISPR/Cas9 approach for knocking out CDH1 in primary human mammary epithelial cells (HMECs). Since primary HMECs did not show robust ER expression, we also re-expressed ER using lentiviral transduction of ESR1 into HMECs. We performed RNAseq from two independent CDH1 targeting gRNAs vs non-targeting gRNA (NTG) control (-/+ ER). Importantly, when comparing the two independent CDH1 gRNAs to NTG there were 2882 shared genes (1436 upregulated only, 1407 downregulated only) that were differentially regulated. Analysis of these shared genes showed the enrichment of estrogen response, PI3K signaling and cell cycle pathways in the CDH1 knockout cells vs control. We also observed the repression of epithelial mesenchymal transition, hypoxia-related genes and p53 in the CDH1 knockout samples vs control. Overall, analysis of the RNAseq data suggests that the loss of E-cadherin in HMECS impacts proliferation and EMT, which will be explored in future studies. In addition, we hope to identify mediators that drive estrogen-induced tumorigenesis using the mouse mammary intraductal (MIND) model, which better recapitulates the progression of ILC and response to estrogen in vivo. We injected control and CDH1 knockout cells into the mammary glands of adult female NSG mice, with estrogen supplemented in their drinking water, and assessed for engraftment using bioluminescence imaging (BLI). BLI suggests enhanced engraftment of CDH1 knockout cells compared to CDH1 wild-type HMECs and a survival advantage for HMECs expressing ESR1. Importantly, analysis of mammary glands two-month post-MIND injections showed engraftment of human cells positive for cytokeratin-5 and lamin a/c. Ongoing studies aim to assess the estrogen response in the CDH1-knockout versus control HMECs in vitro and in vivo to determine whether loss of E-cadherin contributes to ILC-specific ER activity. Understanding the unique interactions between E-cadherin loss and ER in ILC could lead to novel therapeutic approaches for the prevention and treatment of ILC.

Presentation: 6/2/2024
9389 Defining The Effects Of PARP Inhibition On Androgen Receptor Function In Homologous Recombination-Proficient Prostate Cancer
Authors: Wheeler Esmé , Traphagen Nicole , Li Rong , Tewari Alok , Qiu Xintao , Brown Myles
Published: October 2024

Disclosure: E. Wheeler: None. N. Traphagen: None. R. Li: None. A. Tewari: None. X. Qiu: None. M. Brown: None.

Recent clinical trials have explored the combination of androgen receptor (AR) pathway inhibitors and poly (ADP-ribose) polymerase (PARP) inhibitors as a potential treatment for advanced prostate cancer. Despite promising preclinical evidence, this combination therapy has shown limited efficacy in patients with homologous recombination (HR)-proficient tumors. As such, combination AR pathway inhibition and PARP inhibition has been approved by the US FDA only in the HR-deficient setting. To elucidate this discrepancy between preclinical and clinical results, we aimed to comprehensively profile the effects of PARP inhibition on AR function in HR-proficient prostate cancer models. In pursuit of this goal, we conducted experiments using HR-proficient prostate cancer cell lines, including LNCaP, 22RV1, VCaP, LN95, and LNCaP-abl, and assessed the effects of the PARP1/2 inhibitors olaparib, rucaparib, talazoparib, and the PARP1-selective inhibitor AZD-5305. Our findings reveal impacts of PARP inhibitor treatment on AR function. RNA-sequencing analysis demonstrates inhibition of AR transcriptional function in PARP inhibitor-treated cells. Treatment with PARP inhibitors inhibited androgen-induced expression of a subset of genes, with analysis revealing enrichment for Hallmark MYC targets in this gene set. Conversely, treatment with PARP inhibitors also inhibited androgen-induced repression of a subset of genes. However, despite these PARP inhibitor-mediated effects on AR function, our testing of the combination of PARP inhibitors and enzalutamide showed no evidence of synergy or enhanced growth-inhibitory effects at physiologically relevant doses of these inhibitors. Additionally, contrary to previously published data, we observed no evidence that androgen deprivation inhibits the expression of DNA damage response gene sets. This is concordant with the lack of synergy between PARP inhibitors and AR inhibition found in these HR-proficient models. Finally, our analysis comparing PARP1/2 with PARP1-selective inhibitors suggests that these drugs exhibit similar biological effects, both in terms of their growth-inhibitory effects and in modulating AR activity. Collectively, our results indicate that while PARP inhibitors influence AR transcriptional function, they do not synergize with androgen deprivation or AR inhibition in HR-proficient prostate cancer cells.

Presentation: 6/2/2024
12406 Epidemiology Of Multiple Endocrine Neoplasia Type 1 In South Korea: A Nationwide Cohort Study
Authors: Jin Kim Kyoung , Hwang Yoon-a , Heui Yu Min , Moon Shinje , Hong Namki , Rhee Yumie
Published: October 2024

Disclosure: K. Kim: None. Y. Hwang: None. M. Yu: None. S. Moon: None. N. Hong: None. Y. Rhee: None.

Multiple Endocrine Neoplasia Type 1 (MEN1) is one of the rarest endocrine disorders, with a scarcity of comprehensive epidemiological data globally. This deficiency in data is even more pronounced in Asian populations, where MEN1 remains an under-researched area. Therefore, our aim is to identity the prevalence, demographic characteristics, and patterns of comorbidities associated with MEN1.This nationwide cohort study assessed likely MEN1 cases from the Korean National Health Insurance Service database (2003-2020), selected via two operational definitions: one requiring an ICD-10 code for MEN1 (D44.8) and the other mandating at least two related procedures for MEN1-associated conditions (Primary Hyperparathyroidism, Pituitary Adenomas, and Duodenopancreatic Neuroendocrine Tumors). Cases were 1:10 matched by age, sex, and index year with controls who did not have any MEN-1 associated tumors. Our study evaluated 412 patients with likely MEN1 (mean age 43.6 ± 15.8 years; 35.4% male) against an age-sex matched control group of 4,120. Baseline characteristics showed a higher prevalence of comorbidities in MEN1 patients, including diabetes mellitus (22.6% vs 4.8%), hypertension (38.1% vs 16.4%), and dyslipidemia (20.6% vs 11.2%), all with p<0.001. Cancer prevalence was markedly elevated in MEN1 patients across most types, compared to controls. Adrenal involvements were observed in 34.7% of MEN1 patients, with adrenal adenoma being the most common (31.6%). Parathyroid, pituitary, and duodenopancreatic involvements were identified in 58.6%, 22.3%, and 19.9% of MEN1 patients, respectively. Mortality analysis revealed MEN1 patients had a higher mortality rate (16.0 per 1000 person-years) and a younger mean age at death (60.1 years) compared to controls (68.0 years), with an adjusted mortality hazard ratio of 3.1. Additionally, mortality risk varied with organ involvement; parathyroid involvement showed an adjusted HR of 2.7, pituitary involvement 4.7, and duodenopancreas involvement 4.0. The risk increased significantly with multi-organ involvement, where patients affected in more than two organs had HRs from 2.8 to 7.3. Our findings indicate that MEN1 significantly impacts patient morbidity and mortality, necessitating improved surveillance and tailored management to enhance early detection and optimize care for this vulnerable patient group. These insights underscore the pressing need for further research into MEN1 and other rare diseases to advance patient care and outcomes.

Presentation: 6/2/2024
12234 Gα13 Promotes Clonogenic Growth By Increasing Tolerance To Oxidative Metabolic Stress In Prostate Cancer Cells
Authors: Wu Di , Kiang Lim Wei , Chai Xiaoran , Seshachalam Veerabrahma P , Rasheed Suhail A K , Ghosh Sujoy , Casey Patrick J
Published: October 2024

Disclosure: D. Wu: None. W. Lim: None. X. Chai: None. V.P. Seshachalam: None. S.A. Rasheed: None. S. Ghosh: None. P.J. Casey: None.

Gα13 and Gα12 are members of the G12 family of Gα proteins that, along with their associated Gβγ subunits, mediate signaling from specific G protein-coupled receptors. Analyses of tumor specimens indicate that Gα13 expression correlates with patient survival in several solid cancers. We previously reported a role for Gα13 in cell migration and invasion in prostate cancer cell lines. Interestingly, patient data supports the notion that mitochondrial superoxide dismutase 2 (SOD2) correlates with prostate cancer risk and prognostic Gleason scores. Gα13 lower-expressing LNCaP cells also have lower SOD2 protein levels compared to the Gα13 higher-expressing PC3 cells. Hence, we explored the role of Gα13 in prostate tumorigenesis, and its effect on cellular processes such as cell survival and mitochondrial metabolism, in human prostate cancer cell lines PC3 and LNCaP. We stably knocked-down GNA13 expression in PC3 cells and overexpressed GNA13 in LNCaP cells. We found that Gα13 promoted anchorage-independent cell growth in PC3 and LNCaP cell lines, as assessed by soft agar colony formation, spheroid formation, and xenograft tumor growth. Whole-genome transcriptome analyses suggested that Gα13-regulated genes are functionally enriched in the mitochondria compartment and that GNA13 expression positively correlated to SOD2 transcript levels in PC3 cells. We found that silencing GNA13 sensitized PC3 cells to long-term oxidative metabolic stress when cultured in media containing non-glycolytic metabolites, namely galactose, glutamate plus malate, and succinate. Furthermore, Gα13 levels impacted the abundance of SOD2 protein in the mitochondria, as well as SOD2 promoter activity and mRNA expression. In addition, silencing GNA13 increased mitochondrial superoxide levels in PC3 cells when cultured in galactose medium, as assessed by MitoSOX staining and flow cytometry. Moreover, overexpression of SOD2 could rescue the effect of Gα13 loss on suppression of anchorage-independent cell growth in PC3 cells. Importantly, anchorage-independent cell growth was not rescued when a catalytically-inactive SOD2(Q167A) mutant was expressed. Likewise, stable knockdown of SOD2 suppressed the effect of overexpression of Gα13 on anchorage-independent cell growth in LNCaP cells. We propose a novel biological route of Gα13-mediated anchorage-independent growth and response to oxidative metabolic stress through regulation of SOD2 expression in prostate cancer cells. Given that SOD2 protein levels correlate with prostate cancer Gleason grade, identifying the upregulated GPCRs that signal through Gα13 in prostate cancer could lead to novel preventive or therapeutic strategies.

Presentation: 6/1/2024