Liver Function Research Articles

Evaluating the effectiveness of Toxfin and Novasil as dietary aflatoxin-binding agents in broilers for sustaining hepatic antioxidant capacity and intestinal health status during aflatoxin B1 exposure.

To assess the efficacy of Toxfin and Novasil as aflatoxin-binding agents in broilers exposed to aflatoxin B1 (AFB1) from 11 to 30days, 288 mixed-sex Ross 308 broiler chickens were randomly allocated to four dietary groups: control feed, control feed + 0.25mg/kg AFB1, AFB1 feed + 0.3% Toxfin, and AFB1 feed + 0.3% Novasil. The evaluation encompassed growth performance for the grower (11-20days), finisher (21-30days), and overall (11-30days) phases, carcass characteristics, serum biochemical components, liver function enzymes, hepatic antioxidant capacity, AFB1 residue in the liver and kidney, and ileal morphology at 30days, and apparent nutrient digestibility during 29-30days. Exposure to AFB1 significantly resulted in reduced growth efficiency, lowered carcass yields, liver hypertrophy, impaired metabolic and hepatic functions, liver oxidative stress, disrupted ileum architecture, diminished nutrient digestibility, and accumulated AFB1 in the liver and kidney. Conversely, supplementation of Toxfin or Novasil significantly augmented body weight gain (BWG) and reduced feed conversion ratio (FCR) during the finisher and overall phases, elevated BWG in the grower phase, heightened levels of glucose, hepatic protein, and glutathione peroxidase, declined malondialdehyde content, improved apparent metabolizable energy, and lowered AFB1 residues in the liver and kidney. Furthermore, Toxfin inclusion significantly reduced FCR during the grower phase, enhanced European production efficiency factor during the grower and overall phases, augmented dressing percentage, declined proportional liver weight, elevated concentrations of total protein, albumin, and total antioxidant capacity, heightened villus surface area, and boosted crude protein digestibility. To conclude, incorporating 0.3% Toxfin into broilers' feeds confers a more effectual safeguard than Novasil against the deleterious consequences of AFB1 exposure.

Multifunctional biomimetic nanosystem for retinoblastoma treatment

The nanodelivery carrier was modified with tumor cell membrane and dendritic cell membrane to create a double-membrane fusion biomimetic nanomedicine, termed FM@mPDA/DOX/JQ-1. This research introduces a biologically inspired platform for multimodal combined tumor therapy. Because fusion membrane nanomedicines inherit the homologous targeting properties of tumor cells, chemotherapy drugs can be delivered to tumor lesions. In addition, the fusion membrane carries abundant and complete tumor cell membrane antigens. Based on the professional antigen presentation characteristics of dendritic cells, it directly or indirectly promotes the uptake of cell membrane-bound tumor antigens and downstream immune responses. In ectopic and orthotopic tumor-bearing mouse models, FM@mPDA/DOX/JQ-1 can induce a durable immune response to inhibit the rebound of primary tumors after chemotherapy and photothermal therapy (PTT). FM@mPDA/DOX/JQ-1 demonstrates no adverse impact on liver and kidney function, as well as blood indicators in mice, affirming its excellent safety profile. This tumor-specific immunotherapy-based nanoplatform holds promise for extension across various tumor types, offering a viable approach for multimodal combined tumor therapy.

8016 Resolution of Refractory Hypoglycemia Following Pancreatic Solitary Fibrous Tumor Resection

Abstract Disclosure: M.E. Horowitz: None. S. Stefan: None. Introduction: Solitary fibrous tumors (SFT) are exceptionally rare mesenchymal tumors, accounting for only 3.7% of all cases of soft-tissue sarcoma with an incidence of 0.35 cases per 100,000 persons per year. SFT may arise in various anatomical locations, approximately 30% occuring in the abdomen. SFT can manifest with paraneoplastic syndromes, with the most commonly described being non-islet cell hypoglycemia. We present a case of refractory hypoglycemia which resolved following the resection of a large pancreatic SFT. Clinical Case: A 75-year-old male with a history of hypertension presented from oncology clinic with hypoglycemia. Two weeks prior, a 26cm mass of the pancreatic head was identified after he presented to the hospital for one month of abdominal pain and distention, and biopsy of the mass confirmed an SFT. The patient complained of nighttime weakness, confusion, nausea, vomiting, and urinary incontinence for two nights prior to arrival. During this time, the patient had multiple fingersticks showing hypoglycemia below 70 mg/dL, the lowest at 37 mg/dL. On arrival, fingerstick glucose was 38 mg/dL and serum glucose was 27 mg/dL, with a c-peptide level of 0.28 ng/mL (1.00-4.00 ng/mL). Despite hypoglycemia, he was asymptomatic at the time of presentation, indicating hypoglycemia unawareness. Investigation into the cause of hypoglycemia included normal morning cortisol levels, normal thyroid function tests, and normal liver and renal function tests. Further assessment for paraneoplastic disease was conducted, revealing an IGF1 level of 36 ng/dL (5-34 ng/dL) and IGF2 241 ng/dL (267-616 ng/dL), with a ratio of IGF2:IGF1 of 6.7:1. He underwent surgical removal of the large abdominal mass with distal gastrectomy and Billroth-I reconstruction. Pathology was consistent with a 34cm retroperitoneal SFT, STAT6 positivity, and negative margins. Following surgery, the patient did not experience any further hypoglycemia or related symptoms, and glucose ranged 78-135 mg/dL through discharge. Clinical Lessons: Refractory hypoglycemia resulting from a tumor's production of IGF2 is a rare paraneoplastic syndrome known as Doege-Potter Syndrome. This syndrome is observed in fewer than 5% of patients with SFT. The first documented case of hypoglycemia in a patient with "fibrous sarcoma" dates back to 1930. To establish a diagnosis, a ratio of IGF2:IGF1 exceeding 3:1 is suggestive of tumor-mediated production, while a ratio exceeding 10:1 is considered diagnostic. A positive immunohistochemical stain for STAT6 confirms the diagnosis. Patients with these tumors should be routinely monitored for hypoglycemia and related symptoms. Presentation: 6/3/2024

8236 Hepatocyte Vitamin D Receptor (VDR) Regulates Liver Regeneration

Abstract Disclosure: J.E. Gunton: None. Harendran Elangovan [1], Rebecca A. Stokes [1], Jeremy Keane [1], Sarinder Chahal [1], Caroline Samer [1], Miguel Agoncillo [1], Josephine Yu [1], Jennifer Chen [1], Michael Downes 2, Ronald M. Evans 2, Christopher Liddle [1],2, Jenny E. Gunton [1] [1]Centre for Diabetes, Obesity and Endocrinology, The Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, Australia 2 Salk Institute for Biological Studies, La Jolla, CA. USA Background: Vitamin D signals through the vitamin D receptor (VDR) to induce its end-organ effects. Hepatic stellate cells control development of liver fibrosis in response to stressors and vitamin D signaling decreases fibrogenesis. VDR expression in hepatocytes, however, is low in healthy liver, and the role of VDR in hepatocyte proliferation is unclear. Methods: In these studies, hepatocyte-VDR null mice (hVDR) were used to assess the role of VDR and vitamin D signaling in hepatic regeneration. Mice underwent 2/3 partial hepatectomy and liver regeneration and function were studied. Results: hVDR mice had impaired liver regeneration with impaired hepatocyte proliferation. This was associated with significant differential changes in bile salts. Notably, mice lacking hepatocyte VDR had significant increases in expression of conjugated bile acids after partial hepatectomy, consistent with failure to normalize hepatic function by the 14-day time point tested. CDCA (chenodeoxycholate) is an FXR ligand, which was increased after surgery in controls but not in hVDR mice. FXR signaling is important for hepatocyte proliferation. Real-time PCR of hVDR and control livers showed significant changes in expression of cell cycle genes including cyclins D1 and E1 and cyclin-dependent kinase 2. Gene expression profiling of hepatocytes treated with vitamin D or control showed regulation of groups of genes involved in liver proliferation, hepatitis, liver hyperplasia / hyperproliferation and liver necrosis / cell death. Conclusions: Together these studies demonstrate an important functional role for VDR in hepatocytes during liver regeneration. Combined with the known profibrotic effects of impaired VDR signaling in stellate cells, these studies provide a mechanism whereby vitamin D deficiency would both reduce hepatocyte proliferation and permit fibrosis, leading to significant liver compromise. Presentation: 6/2/2024

12450 Beyond the Surface: A Deep Dive into Pancreatic Insulinoma

Abstract Disclosure: S. Bhandari: None. R. Elhag: None. J. Singh: None. N. Rastogi: None. Background: Pancreatic neuroendocrine tumors (NET) are rare lesions that are typically sporadic, solitary and usually <2cm in diameter, with reported incidence of 4 cases per 1 million patients per year[1]. The most common hormone secreting NET are insulinomas. The hallmark of insulinomas is hypersecretion of insulin, leading to neuroglycopenic symptoms and uncontrolled sympathoadrenal activity. Clinical case: 51 years old female with no significant past medical history was referred to endocrine clinic by her primary care physician for hypoglycemia with a blood glucose level of 48 mg/dl. She reported an increased frequency of headaches and dizziness which began with intermittent fasting (10-12 hours) for past 6 months. These symptoms improved upon increasing meal frequency. Initial laboratory investigations revealed glucose of 54 mg/dl, normal HbA1c, and negative sulfonylurea panel. The patient had normal liver and kidney function with no malnutrition or malabsorption issues. Further work up showed C-peptide level 1.56 ng/ml (n 0.80-3.85ng/ml), insulin level 7.9 uIU/mL (n <18.4 uIU/mL), pro-insulin level significantly elevated at 77.6 pmol/L (n </= 18.8pmol/L) and beta hydroxybutyrate of 0.12 mmol/l (n 0.02-0.27mmol/l). Insulin like growth factor was normal. Insulin antibodies were negative, and pituitary hormones were within normal limits. Pancreatic ultrasound was normal. CT abdomen/pelvis showed a 0.8x1.1 cm homogenously hypervascular anterior pancreatic body soft tissue lesion consistent with NET. Patient was started on diazoxide and continuous glucose monitoring (CGM). She was referred to general surgery and underwent successful tumor resection. Insulinoma is suggested by Whipple's triad, which is presence of hypoglycemic symptoms, documented hypoglycemia and resolution of hypoglycemic symptoms after glucose administration. As clinical manifestations are non-specific, diagnosing an insulinoma is challenging and depends on collateral history and a high index of suspicion. The gold standard of diagnosis is supervised 72-hour fasting test with plasma glucose, insulin, C-peptide, and proinsulin level measurements. Medical management of insulinoma includes the use of diazoxide, calcium channel blockers, propranolol, and glucocorticoids. Surgery is definitive treatment for insulinomas, with cure rates ranging from 77 to 100%. Conclusion: Insulinomas are benign and curable in most cases but can be fatal if misdiagnosed. Incidental findings of hypoglycemia should warrant thorough diagnostic workup to facilitate timely diagnosis and management.

VCAM-1 targeted nanocarriers of shRNA-Smad3 mitigate endothelial-to-mesenchymal transition triggered by high glucose concentrations and osteogenic factors in valvular endothelial cells

Endothelial to mesenchymal transition (EndMT) of valvular endothelial cells (VEC) is a key process in the development and progression of calcific aortic valve disease (CAVD). High expression of the Smad3 transcription factor is crucial in the transition process. We hypothesize that silencing Smad3 could hinder EndMT and provide a novel treatment for CAVD. We aimed at developing nanoparticles encapsulating short-hairpin (sh)RNA sequences specific for Smad3 targeted to the aortic valve. We synthesized VCAM-1-targeted lipopolyplexes encapsulating shRNA-Smad3 plasmid (V-LPP/shSmad3) and investigated their potential to reduce the EndMT of human VEC. VEC incubation in a medium containing high glucose concentrations and osteogenic factors (HGOM) triggers EndMT and increased expression of Smad3. Exposed to lipopolyplexes, VEC took up efficiently the V-LPP/shSmad3. The latter reduced the EndMT process in VEC exposed to HGOM by downregulating the expression of αSMA and S100A4 mesenchymal markers and increasing the expression of the CD31 endothelial marker. In vivo, V-LPP/shSmad3 accumulated in the aortic root and aorta of a murine model of atherosclerosis complicated with diabetes, without affecting the liver and kidney function. The results suggest that targeting activated VEC with lipopolyplexes to silence Smad3 could be an effective, novel treatment for CAVD mediated by the EndMT process.

7247 Adrenal Insufficiency In Advanced Cirrhosis: A ‘Shocky’ Clinical Dilemma

Abstract Disclosure: L. Aboishava: None. A. Pareek: None. A. Mertens: None. A. Erokhin: None. Background: In patients with advanced cirrhosis, profound hypoproteinemia can complicate the laboratory assessment of the hypothalamic-pituitary-adrenal axis, but a clinical phenotype of persistent hypotension and suboptimal cortisol response to ACTH stimulation raises the question of whether adrenal insufficiency could also be a contributing factor. Clinical Case: A 65-year-old man with a history of cirrhosis complicated by esophageal varices, ascites, encephalopathy and hepatorenal syndrome was admitted to the ICU with worsening fatigue, profound hypotension, and respiratory arrest. He was started on pressors, antibiotics and was also intubated for a short time. A broad workup was negative for cardiac or infectious causes of shock and showed decreased total protein and albumin (1.6 g/dl (3.5-5.2), with normal serum sodium and potassium. The patient had no previous history of adrenal disease or corticosteroid use. Workup for adrenal insufficiency was initiated and showed decreased morning blood serum cortisol (10.6 ug/dl (2.5-19.5)) and ACTH (<5.0 pg/ml (7.2-63)), as well as suboptimal cortisol response on ACTH stimulation testing (12.5 ug/dl initially, 16.7 ug/dl after stimulation). Head CT on admission was negative for intracranial pathology, and lab results showed normal TSH and mildly increased prolactin of 36.2 ng/ml (4.0-15.0). Pt was started on IV hydrocortisone 50 mg TID. Glucocorticoid therapy didn’t improve his state significantly but was continued with a gradual tapering down of the dose. After intense treatment in the ICU the patient’s state was stabilized. Unfortunately, an endoscopy performed for worsening anemia and blood in stools showed gastric cancer. The patient was transferred to comfort care after a discussion of goals of treatment and died within the next 24 hours. Conclusion: The nature of decreased cortisol levels in patients with cirrhosis is most likely multifactorial, due to impaired hepatic synthetic function, dysregulation of hormone-binding protein balance, abnormal ACTH secretion, and other factors. Impaired corticosteroid-binding globulin synthesis might affect the ratio of globulin-bound and free hormone fractions and alter the accuracy of cortisol assays. Whether adrenal insufficiency is truly one of the complications of advanced cirrhosis contributing to persistent hypotension, or a mere laboratory finding is difficult to answer. It is also yet to be determined whether patients with advanced cirrhosis might benefit from screening and treatment of adrenal insufficiency in circumstances of persistent hypotension, and studies are needed to decide on optimal diagnostic tests to recognize the disease and develop treatment algorithms. Presentation: 6/3/2024

6898 A Case Report Of Drug-Induced Liver Injury Secondary To Sublingual Estradiol In A Transgender Woman

Abstract Disclosure: F. Manas: None. E. Davydov: None. A. Caines: None. K. Estrada: None. J.E. Shill: None. Drug-induced liver injury (DILI), the leading cause of acute liver failure in the United States, occurs in response to a medication or natural compound. Estrogens can lead to idiosyncratic DILI. According to LiverTox [livertox.nih.gov], estrogen has a likelihood score of A (highly likely) to cause DILI, whereas spironolactone has a likelihood score of D (rare). The current formulations of estrogens usually produce a mixed or cholestatic pattern of liver enzyme elevations, however very early, the ALT levels can be markedly elevated (5- to 20-fold). One can be asymptomatic. Often the liver injury resolves after removing the offending agent. We present a case of DILI with elevations of both alanine transferase (ALT) and aspartate transferase (AST), secondary to sublingual estradiol (E2). A 23-year-old transgender female presented for feminizing gender-affirming care. She was started on sublingual E2 2 mg once daily and spironolactone 100 mg orally twice daily. Approximately 14 weeks later, sublingual E2 was increased to 2 mg twice daily for a below-target E2 level, and spironolactone was decreased to 50 mg twice daily due to gas and nausea. Routine blood work three weeks later showed elevated liver function tests (LFTs) in a hepatocellular pattern with ALT of 216 IU/L (normal:<52IU/L), AST of 223 IU/L (normal:<35 IU/L), with normal total bilirubin and alkaline phosphatase. LFTs were normal six months prior. At the time of liver injury, she had consumed six alcoholic beverages in the previous fourteen days, and two doses of acetaminophen. She had no personal history of autoimmunity and no family history of liver disease. Acute hepatitis screen was normal. Abdominal US with liver Doppler was unremarkable. E2 and spironolactone were discontinued. Evaluation by hepatology lead to a diagnosis of DILI from sublingual E2, based on the temporal relationship between initiation of E2 and LFT elevation. Other potential causes of elevated LFTs were excluded. Although she reported alcohol use, the AST/ALT elevation was not in a classic 2:1 pattern. Three weeks after cessation of E2 and spironolactone, her LFTs normalized. Spironolactone was resumed along with E2 by patch, but due to skin-adherence issues she was transitioned to injectable E2 valerate. Her LFTs have remained normal since. This case illustrates a rare but potentially dangerous adverse event of DILI secondary to sublingual E2. Due to the low incidence of liver injury in various studies of individuals with gender incongruence on hormone therapy, current evidence does not support routine liver enzyme monitoring. Clinicians should be aware of the potential risk of liver injury and counsel patients accordingly. As in this case, patients may be successfully rechallenged with the offending DILI medication. Further studies on different formulations of hormone therapy and their effects on the liver would be beneficial in this unique population. Presentation: 6/2/2024

8481 A 32 Year Old Male With Recurrent Acute Pancreatits and Severe Hypertriglyceridemia: Importance of Considering Genetic Variants

Abstract Disclosure: M.F. Salazar Zelaya: None. J.D. Sibaja Jiménez: None. Background : Hypertriglyceridemia is a common medical scenario in daily practice, causing a variety of symptoms including recurrent episodes of acute pancreatits, which can be severe. Multiple genetic variants can lead to different spectrums of the disease. CLINICAL CASE: A 32 year old male police officer presented to our Endocrinology Outpatient Clinic with a history of long standing hypertriglyceridemia and six previous episodes of acute pancreatits, two in the last twelve months. Familiy history was negative for lipid disorders. The patient had adecuate adherence to diet and exercise as well to prescribed medications, which included Fenofibrate 250 mgs/day and Rosuvastatin 40 mgs/day. The patient denied consumption of alcoholic beverages. Recent abdominal ultrasound was reported without abnormalities. His lipid panel reported elevated triglycerides at 5831 mg/dl (n<150 mg/dl), Total Cholesterol normal at 147 (n<200 mg/dl), low HDL levels at 12 mg/dl (range 12-92 mg/dl) and direct LDL Cholesterol at 120 mg/dl. His TSH value was normal at 1.02 uUI/mL (range 0.55-4.78 uUI/mL). Creatinine level was normal at 0.81 mg/dl (range 0.7-1.3 mg/dl). Liver function tests were normal with AST level at 25 IU/L (range 13-39 IU/L) ALT levels at 22 IU/L (range 7-52 IU/L) and alcaline phosphatase at 62 IU/L (range 34-104 IU/L).His fasting glucose level were normal at 82 mg/dl (n<100 mg/dl). Due to a high Familial Chylomicronemia Syndrome clinical score (13 points) we proceeded with genetic analysis of this patient. Next Generation Sequencing for genes related with chylomicronemia (APOA5, APOC2, GPIHBP1,LMFI, LPL) was performed to determine gene sequence plus copy number variation.Two heterocigote variants were reported, both in the LPL gene. The first one: LPL (NM 000237.3) c.644>A;p.Gly215Glu heterozygous is a missense variant already reported in the literature, registered in ClinVar (ID 1522) and the Leiden Open Variation Database. This variant is classified as pathogenic according to criteria PS3, PM1, PP3, PP5 of the American College of Medical Genetics and Genomics. The second one: LPL (nm 000237.3): c.383C>A;p.Thr128Asn;heterozygous is also a missense variant which to the extent of our knowledge has previously been reported only once in the literature: ClinVar (ID 1520537). This variant is classified currently as of unknown clinical significance according to PM2 criteria. There is however and entry reported (PMID: 8778602) of another variant affecting the same codon (p.Thr128AIa) that is associated to chylomicronemia syndrome. Conclusion: In cases of severe hypertriglyceridemia, suspicion and determination of gene variants are of great importance nowadays as they could eventually guide treatment, given the availability in some countries (and currently pending FDA approval) of new pharmacological therapies such as apo C-III inhibitors. Presentation: 6/2/2024

Characterizing metabolomic and transcriptomic changes, and investigating the therapeutic mechanism of Psoralea corylifolia linn. In the treatment of kidney-yang deficiency syndrome in rats

Kidney-yang deficiency syndrome (KYDS) is characterized by a metabolic disorder stemming from neuroendocrine dysregulation, often associated with hepatic dysfunction. In traditional Chinese medicine, Psoralea corylifolia Linn. (BGZ) is commonly utilized for treating KYDS. However, the specific therapeutic effects of BGZ on liver function regulation remain unclear. To evaluate the protective effects of BGZ against KYDS in rats, organ index, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and other biochemical indices were analyzed. Hematoxylin and eosin (HE) staining was utilized to assess liver histopathology. Additionally, transcriptomic and metabolomic analyses were conducted to identify potential biomarkers. BGZ treatment led to a significant reduction in ALT and AST levels, accompanied by improvements in liver histopathology in rats with KYDS. Moreover, BGZ induced significant alterations in 92 differentially expressed genes (DEGs) and 20 metabolites in the KYDS rat model. The comprehensive examination of metabolites and DEGs identified potential mechanisms underlying the therapeutic effects of BGZ, highlighting the neuroactive ligand-receptor interaction, cAMP signaling pathway, calcium signaling pathway, and cytokine-cytokine receptor interaction as key mechanisms. Validation of key targets within the cAMP pathway was substantiated through enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction. The cAMP pathway emerges as a plausible mechanism through which BGZ exerts protective effects against KYDS. The findings of this study contribute to an improved understanding of the therapeutic actions of BGZ and establish a groundwork for further research into the complex pathways involved, as well as the potential for drug-targeted therapies for KYDS.

6849 Insulin Edema in newly diagnosed T1DM Pediatric Patient

Abstract Disclosure: A. Ansar: None. K. McNerney: None. Background: Insulin edema is a rare complication of insulin therapy, especially in the pediatric populations. The pathogenesis is not fully understood but has been linked to Insulin’s role in renal sodium handling and vascular permeability. It has been seen with the initiation of insulin in newly diagnosed patients or the intensification of insulin therapy in those with poor glycemic control.Clinical Case: A previously healthy 12 year old girl presented to the ED with polyuria, polydipsia and fatigue. She was alert and oriented but had kussmaul breathing. She was tachycardic but all other vitals were appropriate. Lab work up showed that she was in DKA with pH 7.07 and bicarbonate 7 mmol/L. Her corrected sodium and electrolytes were normal. Her HbA1C was elevated at 11.7% (4.0-5.6%). Initial fluid resuscitation was performed with 20 mL/kg NS fluids. She was transferred to our Pediatric ICU and was started on the DKA protocol consisting of intravenous insulin infusion at 0.1 unit/kg per hour and 2-bags of dextrose and non-dextrose containing intravenous fluids. She was given a new diagnosis of Type 1 Diabetes. She was transitioned to subcutaneous insulin 22 hours later with multiple daily injections with insulin lispro and glargine, with total dose of insulin at 0.7 unit/kg per day. She was transferred to the general care floor and received diabetes education while in the hospital. On the fifth day after discharge, patient started complaining of leg tightness, puffiness around her eyes and generalized swelling of both feet. She returned to the ED, where she was found to be hemodynamically stable and normotensive with a blood pressure of 113/54 mmHg. Her weight had increased 8.8 kg from the weight at discharge. Her physical exam was notable facial and bilateral periorbital edema, abdominal distension, and 2+ bilateral non-pitting non-tender edema of both legs extending to her medial malleolus. Neurologic exam was performed which was unremarkable. Work up was performed to rule out other causes of edema, including a complete blood count, electrolytes, kidney and liver function tests, all of which were normal. She received 20 mg of furosemide and was instructed to perform fluid restriction to 1 L/m2/day and sodium restriction to <2 grams per day at home. She followed up in clinic 3 days after her ED visit where her weight had decreased by 4.2 kg and her edema had mostly resolved with only 1+ bilateral non-pitting edema. Her total dose of insulin remained at 0.7 unit/kg per day, with acceptable blood glucose levels at home. Her fluid restriction was discontinued and patient was instructed to follow up as usual, and she had no further edema in follow-up. Conclusion: This was a rare case of a newly diagnosed pediatric patient presenting with Insulin edema, which is essential for clinicians to recognize, so they can identify patients presenting with this uncommon side effect to rule out conditions that may present in a similar manner. Presentation: 6/2/2024

8238 Thyroidectomy for Thyroid Storm Complicated by Drug-Induced Hepatotoxicity and Thyrotoxic Cardiopulmonary Disease

Abstract 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

8243 Euglycemic Diabetic Ketoacidosis Unveiled: Delayed Presentation and Complications of SGLT-2 Inhibitor Therapy in a Multimorbid Patient - A Case Report

Abstract Disclosure: T. Amin: None. A.K. Bala: None. M.A. Jones: None. M.S. Akula: None. K. Chalasani: None. M. Patel: None. J. Cheng: None. Introduction: Normal serum glucose levels (<200 mg/dL) in euglycemic diabetic ketoacidosis (EDKA) can complicate the typical clinical presentation of diabetic ketoacidosis (DKA), posing a diagnostic challenge. SGLT-2 inhibitors, a class of antihyperglycemic drugs, have been rarely but significantly associated with EDKA. These inhibitors enhance renal glucose clearance by preventing glucose reabsorption via sodium-glucose cotransport. The increased renal clearance may contribute to the euglycemic picture, potentially leading to an underestimation of required insulin dosage, thereby precipitating ketoacidosis in EDKA. Although the mechanisms of EDKA are not fully understood, the association with SGLT-2 inhibitors is becoming increasingly evident. Case A 53-year-old male with a medical history of type 2 Diabetes Mellitus, coronary artery disease, chronic kidney disease, hyperlipidemia, was admitted to the trauma bay after a fall. Medications included empagliflozin, metformin, aspirin, amlodipine, spironolactone, and carvedilol. Upon presentation, he had a brief loss of consciousness, complained of headache and chest pain, and was found to have an epidural hematoma with regional brain compression on the CT head. Admission labs showed a blood glucose level of 172, an unremarkable anion gap, and normal renal and liver function tests. Due to traumatic brain injury, he was admitted to the ICU for neurological monitoring. Despite remaining neurologically stable, he developed hypoxia, necessitating intubation. After successful extubation, he exhibited worsening metabolic acidosis on the fourth day, with an elevated anion gap of 22 and a blood glucose level of 174. Arterial blood gas analysis revealed a pH of 7.3 (and elevated beta-hydroxybutyrate (>4), while lactic acid levels remained normal. Urine analysis showed elevated blood glucose (>1000) and ketones (>40). Home medications, metformin, and empagliflozin were appropriately withheld, but euglycemic DKA attributed to empagliflozin was diagnosed. Treatment included intravenous fluid resuscitation and insulin infusion, leading to resolution of acidosis and improved mentation within 24 hours. Conclusion: EDKA is a diagnosis of exclusion often overlooked in ICU patients due to diverse causes of high-anion gap metabolic acidosis. Typical cases occur while the patient is using the drug, often associated with triggers like illness, alcohol use, surgery, or starvation. SGLT2 inhibitors, such as empagliflozin, with a half-life of 12.4 hours, are expected to clear the bloodstream in about 48 hours, yet this case suggests an association with EDKA both during use and after drug cessation. This delayed presentation highlights additional risk considerations associated with SGLT2 inhibitors, guiding future clinical diagnoses of EDKA even several days post discontinuation. Presentation: 6/3/2024

Comparative effectiveness of five Chinese patent medicines for non-alcoholic fatty liver disease: A systematic review and Bayesian network meta-analysis

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a metabolically stressed liver injury closely related to insulin resistance and genetic susceptibility and has become the leading chronic liver disease in China. PurposeTo analyze the effectiveness of five Chinese patent medicines used alone or in combination with western medications (WM) for NAFLD using Bayesian network meta-analysis. MethodsSearches were conducted in Embase, Cochrane Library, PubMed, CNKI, Wanfang Database, VIP, and SinoMed for randomized controlled trials (RCTs) on Danning tablets, Huazhi Rougan granules, Dangfei Liganning capsules, Kezhi capsules, and Qianggan capsules, either alone or in combination with WM for NAFLD, up to January 10, 2024. This study was screened based on pre-designed inclusion and exclusion criteria, and the risk of bias was evaluated using the Cochrane ROB2 tool. The primary outcome was clinical efficacy rate, while secondary outcomes included levels of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Triglycerides (TG), and Low-density lipoprotein cholesterol (LDL-C). These data will be analyzed using WinBUGS 1.4.3 and then visualized using Stata 14.0 software. ResultsA total of 77 RCTs involving 7770 patients were included. The results indicated that Huazhi Rougan granules combined with WM (OR = 0.13, 95 % CI 0.05 ∼ 0.26) had a SUCRA probability value of 81.7 %, ranked first in clinical efficacy and significantly improved blood lipids levels including TG, High-density Lipoprotein Cholesterol (HDL-C), and LDL-C, Total cholesterol (TC). For the Chinese patent medicines alone, Danning tablets led with a 75.3 % clinical efficacy rate. Huazhi Rougan granules significantly increased levels of ALT (96.2 %) and AST (MD = -14.48, 95 % CI -23.38 ∼ -5.32). Dangfei Liganning capsules demonstrated significant efficacy in improving TG (73.1 %) and TC (83 %) levels. ConclusionIn the treatment of NAFLD, the combination of Huazhi Rougan granules and WM demonstrated significant clinical effectiveness and improvement in blood lipid profiles. For different outcome indicators, Danning tablets used alone showed the highest clinical efficacy, while significant improvement in liver function indicators was best achieved with Huazhi Rugan granules used alone.

5074 Licorice Root Supplement As A Cause Of Hypokalemic Hypertension

Abstract Disclosure: G. Gill: None. S.M. Harman: None. L.A. Robles: None. A 67-year-old female Veteran presented to an emergency room with a one-day history of high blood pressure, chest tightness, and exertional dyspnea. Her blood pressure was 162/90 mm Hg, pulse regular at 71 BPM, and pain level 5/10. She had a history of hypertension, stable on hydrochlorothiazide alone, hyperlipidemia, anxiety, and depression. Physical exam was benign. EKG revealed normal sinus rhythm at 60 BPM, normal axis, a prolonged QT interval of 510 ms, and no ST changes. Lab evaluation showed a low potassium of 2.4 mEq/L, sodium 145 mEq/L. Other lab measurements (CBC, liver function tests and cardiac enzymes) were within laboratory reference ranges. Medications included topiramate for migraine and over-the-counter supplements for constipation, “thyroid health,” and a topical “testosterone booster” prescribed by a non-allopathic practitioner. Her hypokalemia was attributed to hydrochlorothiazide and topiramate and both were discontinued. She was started on nifedipine for blood pressure control and 40 mEq/day of potassium for hypokalemia. Within 2 weeks of discharge, she presented again with elevated blood pressure and a plasma potassium of 4.0 mMol/L. Further history revealed that her constipation supplement consisted of licorice root (glycyrrhiza glabra) extract 900 mg per capsule, of which she took 3 to 4 capsules daily. The patient was advised to discontinue all supplements. Thyroid function tests were within normal limits. Due to a suspicion of hyperaldosteronism, the ED physician requested an abdominal CT scan which showed a 1 cm, -17.5 Hounsfield unit, right adrenal nodule. Also consistent with hyperaldosteronism, plasma renin activity (PRA) was suppressed at 0.07 ng/mL/hr. However, a serum aldosterone level was less than 1 ng/dL. Her 24-hour urinary metanephrines were normal and a 24-hour urine free cortisol was 31.6 mcg/dL. Morning plasma cortisol was 5.1 mcg/dL. A tentative diagnosis of licorice-induced hyperaldosteronism was made and the patient was treated with a taper of spironolactone. After discontinuing spironolactone, blood pressure was 116/70mmHg and serum potassium was 4.5 mMol/L with a PRA of 0.66 ng/mL/hr and serum aldosterone of <5.0 ng/dL. The syndrome of factitious hyperaldosteronism due to licorice consumption has been well described. The mechanism, inhibition of renal (type 2) 11-beta-hydroxysteroid dehydrogenase by glycyrrhizic acid, allowing cortisol to exercise its considerable mineralocorticoid action, is well understood. Most prior reports have been in patients habitually consuming licorice candy, usually imported, since conventional licorice sold in the U.S. is artificially flavored. Our report illustrates the importance of obtaining a history of use of over-the-counter supplements and assessing their ingredients and the fact that presence of an adrenal nodule and a low PRA does not always indicate endogenous hyperaldosteronism. Presentation: 6/2/2024

6570 Treatment of Cushing’s With Levoketoconazole: A Case Series

Abstract Disclosure: N. Chamorro-Pareja: None. M. Haines: None. L.E. Dichtel: Consulting Fee; Self; Lumos Pharma. Research Investigator; Self; Recordati, NovoNordisk, Perspectum Ltd, Lumos Pharma, Pfizer, Inc.. Stock Owner; Self; Marea Therapeutics. Other; Self; Third Rock Ventures. B.M. Biller: Consulting Fee; Self; Xeris Pharmaceuticals, Recordati Rare Diseases, Sparrow, Lundbeck. Background: Endogenous Cushing’s syndrome (CS) is a rare condition of excess cortisol secretion; the most common cause is a pituitary corticotroph tumor (Cushing’s disease [CD]). Medical treatment for CD is primarily used to control hypercortisolism in patients with persistent or recurrent disease after transsphenoidal surgery (TSS). Levoketoconazole (LKCZ), a steroidogenesis inhibitor, was FDA approved in January 2022 for CS treatment. This reports 3 cases of patients who were treated with LKCZ for recurrent CS. Clinical Cases: Case 1: 44-year-old (yo) male (M) with a history of CD with urinary free cortisol (UFC) >26x upper limit of normal (ULN) who was treated preoperatively with ketoconazole (KCZ) 1000 mg/day with UFC improved to 6x ULN. KCZ was discontinued at TSS, and he achieved remission post-operatively. He was lost to follow-up and re-presented after several years with worsening hypertension, muscle weakness, edema, and anxiety with UFC 28x ULN and a recurrent pituitary lesion on MRI. He declined repeat TSS and underwent radiation therapy (RT) and medical treatment. LKCZ was initiated at 150 mg twice daily (BID) and increased to 300 mg BID. At LKCZ 300 mg BID, he had a low UFC and mild nausea but an adequate serum morning cortisol (10.4 ug/dL, ref:6-18.4 ug/dL); LKCZ was reduced to 150 mg BID with resolution of symptoms (sxs) and normal UFC. Case 2: 56 yo M with a history of CD (UFC >3x ULN) who underwent 2 TSSs and RT over 10 years prior with eventual remission, but later recurred. Sxs included brain fog and mood disturbances. He achieved control with pasireotide but discontinued due to abnormal liver function tests. He was then treated with KCZ 400 mg/day but remained hypercortisolemic (LNSC 1.1x ULN) and was interested in trying a new medication, so was switched to LKCZ 150 mg BID with significant improvement of sxs and normalization of LNSC. Case 3: 54 yo F with presumed cyclic CD (negative whole-body and octreotide scans) with UFC 1.7x ULN and LNSC 3x ULN. TSS was performed with negative pathology; she had persistent hypercortisolemia and sxs including insomnia, fatigue, and mood disturbances. She was intolerant to and/or uncontrolled on 4 medications, including KCZ at 1000 mg/day that was discontinued due to a rash. She was started on LKCZ 150 mg BID and achieved normal LNSC and UFC after about 1 month. The drug was discontinued due to the development of a rash similar to that with KCZ. Conclusion: LKCZ is a new option for the treatment of CS in patients whose disease persists after TSS. These 3 patients had improvement of sxs and normalization of cortisol levels while on LKCZ, although one patient discontinued LKCZ due to a rash that was previously experienced with KCZ. The other two patients are being carefully monitored for liver function test elevation, QTc abnormalities and adrenal insufficiency with no issues to date. To our knowledge, this is the first case series of CS patients treated clinically with LKCZ. Presentation: 6/1/2024

6517 Cardiac Tamponade Secondary to Occult Primary Hypothyroidism

Abstract Disclosure: L. Javed: None. H. Al jumaili: None. A. Mahaldar: None. I. Goyal: None. N. Shakir: None. E. Punni: None. Introduction: The incidence of pericardial effusion in hypothyroidism seems to correlate with severity and duration of the condition and ranges from 3% to 37%. Cardiac tamponade resulting from hypothyroidism is exceptionally rare. We present a case of a patient presenting with this complication.Case Summary:A 38-year-old woman presented during a routine clinic visit with symptoms of fatigue and was found to have elevated liver functions enzymes with ALT 107 (N<48 U/L ) and AST 70 (N<47 U/L)Further evaluation through abdominal imaging revealed incidental finding of a partially imaged moderate pericardial effusion. A subsequent echocardiogram showed circumferential pericardial effusion with early tamponade physiology, necessitating immediate referral to the emergency room (ER) for further assessment and management.Upon admission to the ER, the patient reported progressive fatigue, increased sleep and menorrhagia over 8 months. There were no accompanying symptoms of weight gain or constipation. Family history was positive for thyroid disease in her grandmother. Initial vital signs on admission were Blood pressure: 119/86, Pulse: 55, Respiratory Rate: 13, Temp: 36.7 °C. Electrocardiogram showed sinus bradycardia. Laboratory findings were significant for: Hgb 8.7 (N>11.5), MCV 77.5 (N>80 fL), mildly elevated ALT 56, markedly elevated TSH 255 (N<5 IU/mL), low free T4 <0.1 (N ≥ 0.7 ng/dL), low free T3 <0.6 (N ≥2.0 pg/m), and elevated TPO 472 (N 35 IU/mL). Infectious and rheumatologic work-up were negative. Thyroid ultrasound showed heterogenous echogenicity consistent with thyroiditis.Patient underwent urgent pericardiocentesis draining 750 ml of clear yellowish pericardial fluid. Simultaneously, the patient was initiated on daily levothyroxine at a dose of 112 mcg.Stability in hemodynamics and repeat echocardiogram showcasing no pericardial effusion facilitated the patient’s discharge. Notable improvement with reduction in TSH from 260 to 20 was seen at the one-month follow-up in endocrinology clinic. Conclusion: Hypothyroidism should be considered in patients diagnosed with cardiac tamponade presenting with bradycardia, as in this case. It's been observed that hypothyroidism can affect LFTs which typically resolve with thyroid replacement. Treatment of cardiac tamponade depends on the patient's hemodynamic status. For early mildly affected cases of tamponade, a conservative approach involving close monitoring and limiting fluid intake may suffice, but drainage is often necessary. Since the pericardial effusion and tamponade stem from hypothyroidism, there's a high chance of effusion recurring after drainage. Hence, administering levothyroxine is essential, often leading to effusion resolution within 2-12 months without recurrence. Presentation: 6/3/2024

8197 A Captivating Case Report of Teprotumumab Induced Hyperglycemic Hyperosmolar State

Abstract Disclosure: K.M. Tuna: None. J.P. Perdomo Rodriguez: None. Introduction: Teprotumumab, a monoclonal antibody targeting the IGF-1 receptor, is increasingly utilized for moderate to severe thyroid eye disease. Initial trials noted mild hyperglycemia in patients with diabetes, while recent trials revealed a significant elevation in Hemoglobin A1c (HbA1c) among those with diabetes or pre-diabetes post-infusion. Here, we discuss a case of a patient with diet-controlled diabetes who developed hyperglycemic hyperosmolar state (HHS) two months after Teprotumumab infusion. Case Presentation: A 43-year-old male, with class III obesity, obstructive sleep apnea, dyslipidemia, coronary artery disease, and diet-controlled diabetes (HbA1c 6.5%) presented with worsening proptosis, decreased color vision, severe visual field depression. Laboratory evaluation revealed elevated TSH (6.3 mIU/ml), normal free T4 (0.67 ng/dl, ref: 0.60-1.2 ng/dl), and undetectable Thyroid Stimulating Immunoglobulin (<0.1 IU/L). Blood cell count, renal and liver function tests were normal. Due to high clinical suspicion of thyroid eye disease, he was treated with timolol, dorzolamide, brimonidine, and methylprednisolone 1g daily for 3 days. Glycemic control was achieved with 30 units of daily insulin while on pulse steroids. On outpatient ophthalmology follow-up, Teprotumumab was initiated and he received 2 doses. Eight weeks later, the patient was hospitalized with altered mental status caused by HHS (glucose 617 mg/dl, serum osmolality 316 osm). HbA1c was found to be significantly increased to 12% and the patient required 150 units total daily insulin and metformin upon discharge. Of note, the patient did not have significant weight changes during this time. GAD, IA2, and Zinc Transporter-8 antibodies were obtained prior to discharge and results are pending. Discussion: The IGF-1 receptor, a partial homologue of the insulin receptor, plays a pivotal role in glucose homeostasis. Inhibiting this receptor can lead to hyperglycemia. Initial randomized controlled trials (RCTs) reported a 10% incidence of mild hyperglycemia. A recent RCT from a cohort of 42 patients demonstrated a 50% incidence of hyperglycemia, in which two-thirds of the patients remained in a dysglycemic state with one patient with pre-existing prediabetes developing diabetic ketoacidosis (DKA). Our patient mirrored this scenario with no identifiable confounding factors. Conclusion: Teprotumumab-induced hyperglycemia, though rare, can lead to life-threatening complications. Baseline glycemic assessment, identification of high-risk patients, and comprehensive discussions on risks and benefits are crucial before initiating therapy. Close monitoring, especially in those with prediabetes, is recommended. Patient education plays a pivotal role in early symptom recognition, averting delayed diagnoses, and subsequent hospitalization. Presentation: 6/3/2024

7165 A Case of Severe Myxedema Coma with Levothyroxine Allergy

Abstract Disclosure: A. Rothstein Costris: None. A. Yaseen: None. S. Levy: None. Introduction: Myxedema coma is a life threatening condition with a mortality rate of 25-60%. Untreated, it can lead to fatal physiological changes. The treatment is thyroid hormone replacement therapy, alongside supportive care for complications. Clinical Case: A 65-year-old woman, who has been dealing with untreated hypothyroidism since 2012 and reported allergies to various levothyroxine brands, presented with falls, weakness, and exacerbated leg numbness. During the examination, she exhibited periorbital edema, non-pitting edema in the lower extremities, bradycardia, and hypothermia. The blood work revealed an elevation in TSH levels at 301 uIU/L (0.45-5.33 uIU/mL). The patient was administered IV Synthroid (200 mcg), Atropine, and Hydrocortisone due to concerns about myxedema coma. After four hours, the patient experienced angioedema and hypotension, necessitating intubation. This situation was complicated by a pulseless electrical activity (PEA) arrest. Following cardiopulmonary resuscitation and the administration of epinephrine, the patient achieved return of spontaneous circulation. The allergy team assessed the patient for potential anaphylactic shock from IV Synthroid. Subsequently, the patient was initiated onIV Liothyronine and Hydrocortisone, leading to improvement in mental status over a period of a few weeks, and no adverse effects were reported. Thyroid labs improved to TSH of 53 (0.45-5.33 uIU/mL), FT3 of 3.3 (2.5-4.4 pg/mL) and total T3 of 133 (87-178 ng/dl). Upon discharge, the patient was prescribed Liothyronine, with plans to perform a Levothyroxine desensitization test in the outpatient setting. Conclusion: Myxedema coma is an endocrine emergency. Patients usually present with deteriorating mental status, hypothermia, and multiple organ system abnormalities. The diagnosis relies more on the clinical presentation and physical examination than on laboratory results. Thyroid replacement therapy serves as the cornerstone of treatment, with a preference for T4 due to its greater availability and lower likelihood of adverse events compared to Liothyronine, which may increase the risk of mortality at higher doses. Despite associated risks, incorporating low doses of Liothyronine is still considered in treatment plans, driven by concerns about reduced T4 to T3 conversion in myxedema patients. Hypersensitivity reactions to Levothyroxine are uncommon but may manifest as widespread hives, swelling, eczema-like skin rashes, elevated body temperature, and compromised liver function, with only one case reporting an anaphylactic reaction to Levothyroxine. In summary, the potential for experiencing an anaphylactic reaction to Levothyroxine exists, highlighting the need to contemplate alternative treatments, such as Liothyronine. Desensitization methods can be considered once the patient's condition is stable. Presentation: 6/2/2024

8113 Thyroid Storm in a Patient with Thyroid Nodule on Anticoagulation

Abstract Disclosure: R. Kulkarni: None. S.S. Krishnasamy: None. N. Mon: None. R. Downs: None. Background: There are very few case reports related to hyperthyroidism due to anticoagulation use. We describe a case, of a less common cause of hyperthyroidism due to hemorrhagic thyroiditis in a patient on anticoagulation and history of metastatic colon cancer. Clinical case: A 67-year-old white male with PMH significant for colon cancer with liver metastasis s/p exploratory laparotomy with sigmoid colectomy, end-colostomy with Hartman's pouch creation, pre-diabetes, recent left IJ & axillary vein thrombus on Eliquis, and thyroid nodule; presented with complaints of shortness of breath, difficulty swallowing and dizziness. Other symptoms included weight loss, complaints of heart racing and generalized body aches. The patient had a recent admission for similar complaints and was newly diagnosed with left IJ/axillary vein thrombus and expanding hemorrhagic thyroid nodule on imaging. He was discharged on anticoagulation for the DVT with 2 week follow up for elective thyroidectomy for goiter. The patient was admitted to the ICU for worsened respiratory status needing ventilatory support and pressor support. Physical findings on admission included jaundice, sinus tachycardia, lethargy with agitation. Initial labs showed TSH 0.02 uIU/mL, FT4 4.85 ng/dL and FT3 6.8 pg/mL, LFTs >500 U/L. Burch-Wartofsky Point Scale score was >60 suggestive of thyroid storm. Imaging with PET CT was concerning for thyroid enlargement with multiple nodules with increased uptake. Thyroid US was consistent with heterogenous gland with hemorrhagic nodules. Based on clinical history, physical findings, diagnostic labs, and imaging the patient was diagnosed with severe hyperthyroidism with thyroid storm secondary to hemorrhagic thyroid nodules in the setting of anticoagulation. The patient underwent thyroid artery angiogram with particle embolization of left inferior and right superior thyroid arteries. Endocrinology started the patient on methylprednisolone, cholestyramine and propranolol. Thionamide was held since the patient had abnormal liver function tests in the setting of shock liver. The patient’s thyroid function slowly improved on current regimen to TSH 0.05 uIU/mL, FT4 1.7 ng/Dl and FT3 4.1 pg/mL on day 3. At the family interdisciplinary meeting, due to guarded prognosis, family opted for comfort care, and the patient finally succumbed to multiple co-morbidities. Conclusion: The case presented discusses diagnosis and management of less common causes of hyperthyroidism and management of thyroid storm in liver dysfunction. The patient would have needed a thyroid biopsy at a later date to rule out colonic metastasis as a cause of hemorrhage if he had survived the thyroid storm and comorbid illnesses. Presentation: 6/3/2024