Hyperinsulinemic Hypoglycemia Research Articles

Glucagon-Like Peptide-1 Receptor-Targeted PET/CT With 68 Ga-HBED-CC-Exendin-4 in Localizing Insulinoma : A Head-to-Head Comparison to 68 Ga-NOTA-Exendin-4.

Modifying glucagon-like peptide-1 receptor (GLP-1R)-targeted PET agent to achieve faster renal clearance and preserved high affinity to GLP-1R is clinically relevant. The aim of this study is to assess the performance of a newly developed GLP-1R-targeted agent, 68 Ga-HBED-CC-exendin-4 in localizing insulinoma, and its biodistribution, as compared with previously introduced 68 Ga-NOTA-exendin-4. Nineteen patients with endogenous hyperinsulinemic hypoglycemia were enrolled and referred for 68 Ga-HBED-CC-exendin-4 PET/CT and 68 Ga-NOTA-exendin-4 PET/CT within 2 consecutive days. Diagnostic performance of the 2 tracers in localizing insulinoma was evaluated, and SUV of the lesion, normal pancreas background, kidneys, and bladder were measured. 68 Ga-HBED-CC-exendin-4 and 68 Ga-NOTA-exendin-4 PET/CT exhibited an equivalent efficacy in detection rate (both sensitivity of 100%). Although SUV max of the tumor in 68 Ga-HBED-CC-exendin-4 was significantly lower than that in 68 Ga-NOTA-exendin-4 (20.01 ± 9.41 vs 31.78 ± 15.46, P < 0.001) at 50 minutes postinjection, there was no significant difference in the tumor-to-background ratio between the 2 agents (8.61 ± 3.57 vs 8.18 ± 3.38, P = 0.326), and the lesions could be visible as early as 4 minutes postinjection for both agents in patients who underwent dynamic PET/CT. In addition, 68 Ga-HBED-CC-exendin-4 exhibited approximately 30% decrease of the renal accumulation compared with 68 Ga-NOTA-exendin-4 (SUV mean , 42.21 ± 5.79 vs 58.58 ± 10.06 at 50 minutes, P < 0.001). 68 Ga-HBED-CC-exendin-4 is an effective agent for localizing insulinoma showing similar detectability and tumor-to-background ratio compared with 68 Ga-NOTA-exendin-4. Notably, 68 Ga-HBED-CC-exendin-4 exhibits significantly lower renal uptake than 68 Ga-NOTA-exendin-4, which might potentially benefit the detection of the tumors adjacent to the left kidneys.

Insulin autoimmune syndrome induced by omeprazole in an Asian Male with HLA-DRB1*0406 Subtype: A case report

Insulin autoimmune syndrome (IAS) is characterized by hyperinsulinemic hypoglycemia and elevated anti-insulin antibodies. While thiol-containing drugs commonly induce IAS, cases induced by proton pump inhibitors are rare. We report a case of IAS induced by omeprazole in a 27-year-old Chinese man with the HLA-DRB1*0406 subtype. This patient presented with Whipple’s triad after taking omeprazole without concurrent insulin use. The mixed-meal tolerance test (MMTT) and insulin-C-peptide release tests revealed a rapid surge in insulin levels within one hour, with a non-significant increase in C-peptide and a significant rise in insulin after precipitation. Further examination revealed high-titer positive insulin autoantibodies, leading to a diagnosis of insulin autoimmune syndrome (IAS). Symptoms resolved upon discontinuation of omeprazole and adherence to dietary recommendations, with insulin autoantibody levels decreasing after a 6-month follow-up. This case highlights omeprazole’s potential to induce IAS, underscoring the need for vigilance due to widespread use of proton pump inhibitor.

Insulinoma with suspected mutant somatostatin receptor expression according to histological examination.

This case highlights the possibility of an insulinoma expressing an aberrant form of SSTRs resulting in a discrepancy between the preoperative octreotide assessment and postoperative SSTR expression. Insulinoma is a pancreatic disease that causes hyperinsulinemic hypoglycemia. The first-line treatment is surgery; however, somatostatin derivatives are administered in cases where surgery is not a viable option and to prevent preoperative hypoglycemia. Here, we report a case in which preoperative examination indicated a potential tumor with low somatostatin receptor 2 (SSTR2) and SSTR5 expression, whereas postoperative pathological examination indicated strong SSTR expression. We report the case of a 69-year-old Japanese female who experienced hypoglycemia-like symptoms for a decade such as sweating, fatigue, hunger, and confusion with an increase in episode frequency per year. Dynamic computed tomography revealed a 13-mm diameter nodule and aberrant blood flow in the pancreatic tail. Subsequently, the patient was diagnosed with pancreatic insulinoma. A preoperative octreotide test did not relieve hypoglycemia, and no uptake of 111indium-pentetreotide was observed, suggesting an insulinoma with low SSTR expression. However, postoperative histological studies suggested that the intracellular domain of SSTRs were highly expressed, while the extracellular domain may be mutated. We present a rare case of insulinoma expressing an aberrant form of SSTRs resulting in a discrepancy between the preoperative octreotide assessment and postoperative SSTR expression.

Improved Localization of Insulinomas Using 68Ga-NODAGA-Exendin-4 PET/CT.

Precise anatomic localization of insulinomas is crucial for surgical treatment. Current routine noninvasive imaging techniques, including CT, MRI, and 68Ga-DOTA-somatostatin analog (DOTA-SSA) PET/CT, have limited sensitivity. Endoscopic ultrasound is highly sensitive but invasive. In this prospective multicenter study, we compared the diagnostic accuracy of 68Ga-NODAGA-exendin-4 (exendin) PET/CT with all routine imaging procedures for the localization of insulinomas. Methods: Sixty-nine adults with biochemically proven adult endogenous hyperinsulinemic hypoglycemia underwent exendin PET/CT and current routine imaging. Images were evaluated in a clinical reading and in an expert reading. Image quality was determined by quantitative analysis. Results: Based on clinical readings, the accuracy of exendin PET/CT (94.4%; 95% CI, 84.6%-98.8%) was greater than that of DOTA-SSA PET/CT (64.8%; 95% CI, 50.6%-77.3%), contrast-enhanced CT/contrast-enhanced diffusion-weighted imaging-MRI (83.3%; 95% CI, 70.7%-92.1%), and endoscopic ultrasound (82.8%; 95% CI, 64.1%-94.1%). In 13% of patients, a correct diagnosis was only reached after exendin PET/CT. Interobserver agreement between readings was higher for exendin PET/CT than for DOTA-SSA PET/CT and contrast-enhanced CT/contrast-enhanced diffusion-weighted imaging-MRI (Cohen κ, 1.0 vs. 0.5 and 0.55). Exendin PET/CT provided a higher insulinoma-to-background ratio (15.3 ± 6.7 vs. 5.2 ± 3.0) and contrast-to-noise ratio (22.6 ± 11.1 vs. 5.1 ± 3.7) than did DOTA-SSA PET/CT. Conclusion: This study demonstrates the superiority of exendin PET/CT in a unique prospective comparison to all current routine imaging modalities for preoperative localization of benign insulinomas, providing the level of evidence needed for clinical implementation.

Crashing into Discovery: Nesidioblastosis in Adult, Unmasked post-Motor Vehicle Accident - A Case Study and Literature Review

Abstract Introduction/Objective Nesidioblastosis, characterized by pancreatic duct-derived B-islet cell proliferation, typically manifests with hypoglycemic symptoms. While more common in newborns, it can rarely affect adults. Here, we report an incidental finding of nesidioblastosis in a 37-year-old female following abdominal trauma due to a motor vehicle crash (MVC). Methods/Case Report A 37-year-old female with no notable medical history presented with blunt abdominal trauma following an MVC. The emergency evaluation revealed a grade 4 traumatic splenic laceration and severe hemoperitoneum. Preoperative lab results showed decreased hemoglobin, elevated white cell count, prolonged prothrombin time, and reduced calcium and magnesium levels. The patient underwent a splenectomy along with a distal pancreatectomy. While grossly unremarkable, microscopic examination revealed maintained acinar architecture with focal hyperplasia around pancreatic ducts. Enlarged acinar cells with pleomorphic nuclei and prominent nucleoli were consistent with focal nesidioblastosis. Results (if a Case Study enter NA) NA Conclusion Multiple studies have documented the first reported case of nesidioblastosis in adults was in 1975. While its exact incidence is uncertain, most sources suggest a relative frequency of 0.5 – 7% of persistent hyperinsulinemic hypoglycemia, with estimated overall an annual rate of around 9 per 100,000, with a higher occurrence among females. This unusual incidental discovery of nesidioblastosis in an asymptomatic patient undergoing pancreatic resection for unrelated reasons highlights the likelihood of underestimating the actual prevalence of this disease.

6799 RZ358 Therapy. A Novel Approach to Hyperinsulinemia in Metastatic Neuroendocrine Tumor Patients

Abstract Disclosure: J. Noreña: None. T. Akcan: None. S. Patel: None. W. Madeleine: None. S. Shaheen: None. M. Tan: None. RZ358, an intravenously administered monoclonal antibody, targets a unique allosteric site on the insulin receptor. It is under investigation for hypoglycemia due to congenital hyperinsulinism. We present a case of its efficacy in treating refractory hyperinsulinemic-hypoglycemia (HH) due to a metastatic pancreatic neuroendocrine tumor (pNET). Clinical Case: A 50-year-old woman with a 6-year history of HH initially presented in 2016 with epigastric pain and was diagnosed with gastrin secreting pNET pT3N1. After Whipple surgery and cholecystectomy. A well-differentiated, WHO grade 2 NET, positive in immunohistochemistry for AE1/3, synaptophysin and Ki-67 index of 9.2% was confirmed. She presented recurrent disease with liver metastasis requiring somatostatin analogue Lanreotide. Subsequently despite Lanreotide, hypoglycemia persisted, and 72-hour fast confirmed HH. DOTATATE scan showed progression to new liver lesions. Everolimus was started and subsequently peptide receptor radionuclide therapy (PRRT) with fair hypoglycemia control. Unfortunately, her disease progressed. Oral glucose, cornstarch, and diazoxide failed. After a left hepatectomy and transarterial chemoembolization, her severe hypoglycemia improved briefly. Despite high-dose dexamethasone (up to 4 mg daily), octreotide 400 mcg every 8 hours, and high-calorie total parenteral nutrition (TPN) (over 800 grams of carbohydrates daily), she required multiple hospitalizations for persistent symptomatic hypoglycemia. Moreover, these therapies led to significant side effects, including recurrent episodes of volume overload, 240 pounds weight gain over a year, and Cushingoid features. Given RZ358's reports in reversing HH in rodents, humans, and a recent report of successful use in a malignant insulinoma case, we aimed to start RZ358 in our patient. We obtained, emergency use authorization from the FDA, IRB of Stanford University School of Medicine approval, and patient written informed consent. RZ358 was started at 6 mg/kg biweekly, along with octreotide, dexamethasone, and TPN. RZ358 dosage was later increased to 9 mg/kg weekly, allowing a substantial reduction in dexamethasone to physiological doses and a 50% reduction in TPN carbohydrate requirements. She achieved normoglycemia and returned home, but missing a single weekly RZ358 dose caused recurrent severe hypoglycemia until the next dose administration.As her disease progressed, the patient opted for comfort care, discontinuing TPN and RZ358. Conclusion: RZ358 represents a novel and unique treatment option for refractory HH in patients with metastatic NETs and can improve clinical outcomes when standard interventions fail. This case underscores the potential of RZ358, a monoclonal antibody, to treat HH beyond its approved use for congenital cases, suggesting its applicability to cases of hyperinsulinemia secondary to NETs in adults. Presentation: 6/2/2024

9286 RZ358 Therapy. A Novel Approach To Hyperinsulinemia In Metastatic Neuroendocrine Tumor Patients

Abstract Disclosure: J. Noreña: None. T. Akcan: None. S. Patel: None. M. Welsh: None. S. Shaheen: None. M. Tan: None. RZ358, an intravenously administered monoclonal antibody, targets a unique allosteric site on the insulin receptor. It is under investigation for hypoglycemia due to congenital hyperinsulinism. We present a case of its efficacy in treating refractory hyperinsulinemic-hypoglycemia (HH) due to a metastatic pancreatic neuroendocrine tumor (pNET). Clinical Case: A 50-year-old woman with a 6-year history of HH initially presented in 2016 with epigastric pain and was diagnosed with gastrin secreting pNET pT3N1. After Whipple surgery and cholecystectomy. A well-differentiated, WHO grade 2 NET, positive in immunohistochemistry for AE1/3, synaptophysin and Ki-67 index of 9.2% was confirmed. She presented recurrent disease with liver metastasis requiring somatostatin analogue Lanreotide. Subsequently despite Lanreotide, hypoglycemia persisted, and 72-hour fast confirmed HH. DOTATATE scan showed progression to new liver lesions. Everolimus was started and subsequently peptide receptor radionuclide therapy (PRRT) with fair hypoglycemia control. Unfortunately, her disease progressed. Oral glucose, cornstarch, and diazoxide failed. After a left hepatectomy and transarterial chemoembolization, her severe hypoglycemia improved briefly. Despite high-dose dexamethasone (up to 4 mg daily), octreotide 400 mcg every 8 hours, and high-calorie total parenteral nutrition (TPN) (over 800 grams of carbohydrates daily), she required multiple hospitalizations for persistent symptomatic hypoglycemia. Moreover, these therapies led to significant side effects, including recurrent episodes of volume overload, 240 pounds weight gain over a year, and Cushingoid features. Given RZ358's reports in reversing HH in rodents, humans, and a recent report of successful use in a malignant insulinoma case, we aimed to start RZ358 in our patient. We obtained, emergency use authorization from the FDA, IRB of Stanford University School of Medicine approval, and patient written informed consent. RZ358 was started at 6 mg/kg biweekly, along with octreotide, dexamethasone, and TPN. RZ358 dosage was later increased to 9 mg/kg weekly, allowing a substantial reduction in dexamethasone to physiological doses and a 50% reduction in TPN carbohydrate requirements. She achieved normoglycemia and returned home, but missing a single weekly RZ358 dose caused recurrent severe hypoglycemia until the next dose administration.As her disease progressed, the patient opted for comfort care, discontinuing TPN and RZ358. Conclusion: RZ358 represents a novel and unique treatment option for refractory HH in patients with metastatic NETs and can improve clinical outcomes when standard interventions fail. This case underscores the potential of RZ358, a monoclonal antibody, to treat HH beyond its approved use for congenital cases, suggesting its applicability to cases of hyperinsulinemia secondary to NETs in adults. Presentation: 6/2/2024

6799 RZ358 Therapy. A Novel Approach To Hyperinsulinemia In Metastatic Neuroendocrine Tumor Patients

Abstract Disclosure: J. Noreña: None. T. Akcan: None. S. Patel: None. W. Madeleine: None. S. Shaheen: None. M. Tan: None. RZ358, an intravenously administered monoclonal antibody, targets a unique allosteric site on the insulin receptor. It is under investigation for hypoglycemia due to congenital hyperinsulinism. We present a case of its efficacy in treating refractory hyperinsulinemic-hypoglycemia (HH) due to a metastatic pancreatic neuroendocrine tumor (pNET). Clinical Case: A 50-year-old woman with a 6-year history of HH initially presented in 2016 with epigastric pain and was diagnosed with gastrin secreting pNET pT3N1. After Whipple surgery and cholecystectomy. A well-differentiated, WHO grade 2 NET, positive in immunohistochemistry for AE1/3, synaptophysin and Ki-67 index of 9.2% was confirmed. She presented recurrent disease with liver metastasis requiring somatostatin analogue Lanreotide. Subsequently despite Lanreotide, hypoglycemia persisted, and 72-hour fast confirmed HH. DOTATATE scan showed progression to new liver lesions. Everolimus was started and subsequently peptide receptor radionuclide therapy (PRRT) with fair hypoglycemia control. Unfortunately, her disease progressed. Oral glucose, cornstarch, and diazoxide failed. After a left hepatectomy and transarterial chemoembolization, her severe hypoglycemia improved briefly. Despite high-dose dexamethasone (up to 4 mg daily), octreotide 400 mcg every 8 hours, and high-calorie total parenteral nutrition (TPN) (over 800 grams of carbohydrates daily), she required multiple hospitalizations for persistent symptomatic hypoglycemia. Moreover, these therapies led to significant side effects, including recurrent episodes of volume overload, 240 pounds weight gain over a year, and Cushingoid features. Given RZ358's reports in reversing HH in rodents, humans, and a recent report of successful use in a malignant insulinoma case, we aimed to start RZ358 in our patient. We obtained, emergency use authorization from the FDA, IRB of Stanford University School of Medicine approval, and patient written informed consent. RZ358 was started at 6 mg/kg biweekly, along with octreotide, dexamethasone, and TPN. RZ358 dosage was later increased to 9 mg/kg weekly, allowing a substantial reduction in dexamethasone to physiological doses and a 50% reduction in TPN carbohydrate requirements. She achieved normoglycemia and returned home, but missing a single weekly RZ358 dose caused recurrent severe hypoglycemia until the next dose administration.As her disease progressed, the patient opted for comfort care, discontinuing TPN and RZ358. Conclusion: RZ358 represents a novel and unique treatment option for refractory HH in patients with metastatic NETs and can improve clinical outcomes when standard interventions fail. This case underscores the potential of RZ358, a monoclonal antibody, to treat HH beyond its approved use for congenital cases, suggesting its applicability to cases of hyperinsulinemia secondary to NETs in adults. Presentation: 6/2/2024

9286 RZ358 Therapy. A Novel Approach to Hyperinsulinemia in Metastatic Neuroendocrine Tumor Patients

Abstract Disclosure: J. Noreña: None. T. Akcan: None. S. Patel: None. M. Welsh: None. S. Shaheen: None. M. Tan: None. RZ358, an intravenously administered monoclonal antibody, targets a unique allosteric site on the insulin receptor. It is under investigation for hypoglycemia due to congenital hyperinsulinism. We present a case of its efficacy in treating refractory hyperinsulinemic-hypoglycemia (HH) due to a metastatic pancreatic neuroendocrine tumor (pNET). Clinical Case: A 50-year-old woman with a 6-year history of HH initially presented in 2016 with epigastric pain and was diagnosed with gastrin secreting pNET pT3N1. After Whipple surgery and cholecystectomy. A well-differentiated, WHO grade 2 NET, positive in immunohistochemistry for AE1/3, synaptophysin and Ki-67 index of 9.2% was confirmed. She presented recurrent disease with liver metastasis requiring somatostatin analogue Lanreotide. Subsequently despite Lanreotide, hypoglycemia persisted, and 72-hour fast confirmed HH. DOTATATE scan showed progression to new liver lesions. Everolimus was started and subsequently peptide receptor radionuclide therapy (PRRT) with fair hypoglycemia control. Unfortunately, her disease progressed. Oral glucose, cornstarch, and diazoxide failed. After a left hepatectomy and transarterial chemoembolization, her severe hypoglycemia improved briefly. Despite high-dose dexamethasone (up to 4 mg daily), octreotide 400 mcg every 8 hours, and high-calorie total parenteral nutrition (TPN) (over 800 grams of carbohydrates daily), she required multiple hospitalizations for persistent symptomatic hypoglycemia. Moreover, these therapies led to significant side effects, including recurrent episodes of volume overload, 240 pounds weight gain over a year, and Cushingoid features. Given RZ358's reports in reversing HH in rodents, humans, and a recent report of successful use in a malignant insulinoma case, we aimed to start RZ358 in our patient. We obtained, emergency use authorization from the FDA, IRB of Stanford University School of Medicine approval, and patient written informed consent. RZ358 was started at 6 mg/kg biweekly, along with octreotide, dexamethasone, and TPN. RZ358 dosage was later increased to 9 mg/kg weekly, allowing a substantial reduction in dexamethasone to physiological doses and a 50% reduction in TPN carbohydrate requirements. She achieved normoglycemia and returned home, but missing a single weekly RZ358 dose caused recurrent severe hypoglycemia until the next dose administration.As her disease progressed, the patient opted for comfort care, discontinuing TPN and RZ358. Conclusion: RZ358 represents a novel and unique treatment option for refractory HH in patients with metastatic NETs and can improve clinical outcomes when standard interventions fail. This case underscores the potential of RZ358, a monoclonal antibody, to treat HH beyond its approved use for congenital cases, suggesting its applicability to cases of hyperinsulinemia secondary to NETs in adults. Presentation: 6/2/2024

8207 Insights From a Case of Insulinoma and Possible Genetic Variants in a Young Woman With Recurrent Hypoglycemia

Abstract Disclosure: M.A. Brandao: None. A. Bharara: None. V.I. Moncada Castro: None. T.C. Tsai: None. Y. Wu: None. S. Marquez Flores: None. K. Divari: None. Introduction: Insulinomas are neuroendocrine neoplasms causing hyperinsulinemic hypoglycemia. They are rare, with a prevalence of 1-4 people per million of the general population. Key features are symptoms of hypoglycemia, low plasma glucose, and symptom relief by correcting hypoglycemia. Here, we report a patient with recurrent hypoglycemia who was found to have insulinoma. Several variants of uncertain significance (VUS) were detected in this patient. This gives us some insights into a broader perspective. Clinical case: A 28-year-old healthy female was found unresponsive by her partner. Blood glucose (BG) was 40 mg/dL when paramedics arrived. She received dextrose and rapidly recovered. She was briefly hospitalized and received glucose infusion with improvement. Subsequently, the patient developed episodes of blurry vision and weakness. She had been eating more frequently to prevent symptoms. Her weight was stable at 65.77 kg. She had not been on any medications. She continued to experience hypoglycemic episodes with BG dropping to 30 mg/dL, so she sought evaluation from an endocrinologist. Laboratory work-up showed Proinsulin of 530.6 pmol/L, C-peptide 5 ng/ml, TSH 1.01 mciu/ml, Beta-hydroxybutyrate (BHOB) 0.7 mg/dL, hemoglobin A1c 4.7%, calcium 8.9 mg/dL, albumin 4.1. Abdominal computed tomography (CT) scan showed an 11 mm nodule anterior to the pancreatic tail. No discrete calcification was noted. Magnetic resonance imaging (MRI) of the abdomen redemonstrated the 10 x 6mm, slightly exophytic lesion in the pancreatic tail. Therefore, she underwent laparoscopic enucleation with pathology showing a 1.7cm well-differentiated grade 2 neuroendocrine tumor, with positive margins. Given its indolent nature, further surgical resection was not recommended. Germline testing showed several VUS: the AXIN2 gene (c.1822C&amp;gt;G), GPC3 gene (c.565G&amp;gt;T), NF2 gene (c.296A&amp;gt;G), RECQL4 gene (c.2791C&amp;gt;G). However, no pathogenic variants were identified. Surveillance MRI of the abdomen six months after the surgery has shown no evidence of recurrent disease. The patient has remained euglycemic and symptoms have not recurred. Conclusion: Insulinomas are typically sporadic but may occur due to an activating T372R mutation in the Yin Yang. It may also occur in the setting of multiple endocrine neoplasia type 1 (MEN-1) syndrome caused by MEN1 gene mutations. Although no pathogenic variant mutations associated with insulinoma were found, several VUS that have not yet been described as related to insulinoma were detected in this patient. Routine genetic testing in newly diagnosed patients is not always recommended. Therefore, further efforts are required to understand genetic mutations and epigenetic modifiers associated with insulinoma. Validation of identified VUS and additional genetic testing in young patients with insulinoma are crucial. Presentation: 6/2/2024

9194 Generation of a Human-Induced Pluripotent Stem Cell Line From a Patient With Hypopituitarism and a Novel Nonsense Variant in FOXA2

Abstract Disclosure: M.A. Camilletti: None. G.T. Chirino Felker: None. G. Amin: None. S. Castañeda: None. F. Zabalegui: None. C. Romano Florit: None. A. Waisman: None. M. Ciaccio: None. M.I. Di Palma: None. E. Vaiani: None. A. Belgorosky: None. S.G. Miriuka: None. L.N. Moro: None. M.I. Perez-Millan: None. Congenital Hypopituitarism (CH) is a genetically complex disease characterized by one or more pituitary hormone deficiencies. Forkhead Box A2 (FOXA2, 600288) is a pioneer transcription factor associated with development of multiple tissues in humans and mice. Heterozygous loss of function mutations in FOXA2 were recently shown to cause CH with hyperinsulinemic hypoglycemia, but little is known about the molecular mechanism of FOXA2 action during pituitary development. We identified a novel, heterozygous nonsense variant in FOXA2 (c.686C&amp;lt;A; p.S229X) in a patient diagnosed with GH deficiency at 1.7 years of age, with anterior lobe hypoplasia and absent pituitary stalk, asymptomatic hypoglycemia, and craniofacial malformations. To discover the mechanism of FOXA2 regulation of pituitary development we generated an induced pluripotent stem cell line (FOXA2mut-iPSC) from the patient’s polymorphonuclear blood cells (PBMCs) using an EF1a-hSTEMCCA-loxP vector containing the pluripotency genes OCT-4, SOX-2, c-MYC and KLF4. FOXA2mut-iPSC clone R1 had a normal karyotype and embryonic stem cell-like morphology. These cells express endogenous pluripotency-associated markers NANOG, SOX2, and OCT4, have alkaline phosphatase activity, and can differentiate into all three developmental layers, indicating that these cells are pluripotent. Short tandem repeat (STR) analysis confirmed that FOXA2mut-iPSC R1 clone profiles matched those of the donor PBMCs. Next, we compared pituitary differentiation of FOXA2mut-iPSC vs. control-iPSCs in vitro. Cells were cultured in a differentiation medium containing BMP4, the smoothened agonist SAG, and fibroblast growth factor (FGF), as described in Zimmer et al., 2016 (1). Gene expression analysis (by qRT-PCR) of samples collected on days 0, 4, 7, and 15 of the differentiation protocol showed an increased expression of genes associated with anterior pituitary development including OTX2, PITX1/2, and SIX1 in both cell lines (n=2). These preliminary data suggest that pituitary cell fate can be induced in the heterozygous FOXA2mut-iPSC clone. Ongoing studies will assess pituitary hormone-producing cell differentiation after longer periods of FOXA2mut-iPSC cell culture. In sum, patient iPSC differentiation is a promising tool for assessment of normal and variant FOXA2 function in human pituitary development, and for enlightening the mechanisms of FOXA2 action in human pituitary development. (1) Zimmer et al., Stem Cell Reports. 2016 Jun 14;6(6):858-872. Presentation: 6/1/2024

8262 Non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS) after gastric sleeve surgery

Abstract Disclosure: R.E. Thomas: None. A. Charales: None. B. Bangash: None. S. Haider: None. S. Ouais: None. Introduction: Non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS) is a rare condition characterized by endogenous hyperinsulinemic hypoglycemia after meals. This article explores NIPHS, emphasizing its occurrence post-gastric sleeve surgery. We delve into clinical features, diagnosis, treatment, and challenges, using a case presentation to illustrate complexities.Clinical Features and Classification:NIPHS entails endogenous hyperinsulinemic hypoglycemia without islet cell neoplasms, featuring islet cell hypertrophy. Formerly "Nesidioblastosis," post-RYGB cases constitute a distinct diagnosis. Common features include postprandial hyperinsulinemic hypoglycemia, negative radiologic localization, and a positive calcium stimulation test.Patients present postprandial hypoglycemia 2-4 hours after meals, with symptoms like tachycardia, tremors, confusion, and occasional seizures. Lab findings include elevated insulin, C peptide, and pro-insulin, low beta-hydroxybutyrate, and negative sulfonylurea/meglitinide screen.Diagnostic Workup:Evaluate glucose, insulin, pro-insulin, C peptide, beta-hydroxybutyrate, and sulfonylurea/meglitinide. Ultrasound differentiates insulinoma from diffuse processes. If negative, conduct SACST for localization.Case Presentation:A 37-year-old female post-gastric sleeve surgery presented with severe hypoglycemia. Symptoms included confusion, nausea, and palpitations, occurring postprandially, relieved by food or juice. Glucagon was administered, and consultations sought. Diazoxide stabilized blood glucose.Treatment Modalities:Dietary modifications reduce free carbohydrate intake, spaced meals minimize hyperinsulinemic episodes. Medical management (octreotide, verapamil, diazoxide, acarbose) proves effective, especially post-gastric bypass. Sub-total pancreatectomy is considered in severe refractory cases.Multidisciplinary Approach:Management involves endocrinologists, surgeons, radiologists, and dietitians. Regular monitoring assesses efficacy, adjusts medications, and addresses complications. Challenges and Future Perspectives: NIPHS complexities include variable presentation and diagnostic challenges. Research should refine criteria, explore interventions, and understand pathophysiology. Conclusion: Non-insulinoma pancreatogenous hypoglycemia syndrome, especially post-gastric sleeve surgery, presents complexities. This exploration highlights clinical aspects, diagnostics, and management challenges, emphasizing the need for a multidisciplinary approach. Continued research aims to enhance diagnostic precision and improve outcomes for those affected by this intriguing syndrome. Presentation: 6/3/2024

6538 Find me if you can! A Case of a "Well Placed Solitary Insulinoma" in "The Center" of an SACST

Abstract Disclosure: R. Kennedy: None. D.A. D'Alessio: None. A.V. Vella: None. Introduction: Selective arterial calcium stimulation testing (SACST) can be utilized in patients to localize solitary insulinomas when imaging is non diagnostic. While a heterogenous stimulation pattern suggests NIPHS, or multiple insulinomas this case uniquely demonstrates such a pattern with a solitary insulinoma. Clinical Case: The patient is a 48 year old female who presented to the emergency department (ED) for bizarre behavior which resolved with a sweetened drink. Serum glucose was 62 mg/dL, she was treated with IV dextrose and was discharged from the ED. She was referred to outpatient endocrinology for further evaluation where continuous glucose monitoring confirmed predominantly fasting hypoglycemia. Adrenal insufficiency was excluded. She was admitted for a 72 hour inpatient fast where the patient achieved hypoglycemia within 24 hours, with glucose 46 mg/dL (associated with neuroglycopenic symptoms), beta hydroxybutyrate &amp;lt; 0.18 mmol/L, insulin 3.9 mcIU/mL, proinsulin 157pmol/L, c-peptide 1.4 ng/mL and a glucose rise greater than 25mg/dL after glucagon administration. Sulfonylurea screen and insulin antibodies were negative; IGF1 within normal limits. These labs were consistent with hyperinsulinemic hypoglycemia. An MRI pancreas however did not reveal an insulinoma. The patient therefore underwent a SACST, demonstrating a 10 fold response in the territory of the gastroduodenal artery and splenic artery, as well as a 3 fold response in the superior mesenteric artery. This heterogenous pattern in addition to the marked response in each arterial territory raised the possibility of multiple insulinomas. However as there were no tumors present on imaging, medical management was initiated with close follow up. She was trialed with months of somatostatin analogs and diazoxide with minimal improvement in the frequency and severity of her hypoglycemia. About a year after her initial diagnosis, repeat abdominal imaging (CT and MRI) revealed an 8 mm arterial hyper-enhancing lesion in the body of the pancreas concerning for neuroendocrine tumor. Repeat SACST was performed, this time showing a greater than 10 fold response in all three arterial territories. Angiography showed a tumor blush that was visible when each of the three major arteries were injected sequentially. She underwent laparoscopic pancreatic enucleation. The lesion was located on the body of the pancreas, with histology confirming an insulinoma. The patient responded promptly post operatively; her symptoms resolved without further need of medical management. Conclusion: Our case shows that the interpretation of an SACST should take into account the arterial anatomy before ascribing a non-focal response to multiple territories of insulin hypersecretion. Presentation: 6/1/2024

8396 Growth Hormone Secretion after Glucagon Stimulation is Increased in Individuals with History of Bariatric Surgery

Abstract Disclosure: L. Pei: None. C. Cummings: None. H. Saeed: None. M. Farahmandsadr: None. A. Amore: None. A. Sheehan: None. R. Ferraz-Bannitz: None. D.C. Simonson: Stock Owner; Self; GI Windows. Other; Self; wife owns Phase V Technologies. M. Patti: Advisory Board Member; Self; data and safety monitoring board on Fractyl Health. Consulting Fee; Self; AstraZeneca, Hamni, MBX Biosciences. Grant Recipient; Self; Receive investigator-initiated research funding from Dexcom. Background: Growth hormone (GH) is an important counterregulatory hormone and regulator of hepatic glucose metabolism. Previous studies demonstrated increased plasma GH and reduced plasma growth hormone receptor (GHR) after bariatric surgery in both rodents and humans. Moreover, plasma GHR was identified as mediator of improved glycemic control after Roux-en-Y gastric bypass (RYGB). We now test the hypothesis that altered GH and/or GHR levels contribute to post-bariatric hypoglycemia (PBH). Methods: Cross-sectional studies were performed at a single academic institution. GH secretion was assessed after 1mg IV glucagon (GCG) and during hyperinsulinemic-hypoglycemic clamp in 3 groups: 1) post-RYGB without hypoglycemia symptoms (RnonH) (20F, age 51±11 (mean±SD) y, BMI 35±8 kg/m2, HbA1c 5.2±0.3%, 10.6±5.3 years post-surgery), 2) PBH (18F/2M, age 54±12y, BMI 30.5±4.6 kg/m2, HbA1c 5.2±0.3%, 9.4±6.0 years post-surgery), 3) weight-similar controls without upper GI surgery (CON) (6F/4M, age 47.1±13.1y, BMI 31.9±5.7 kg/m2, HbA1c 5.4±0.3%). Plasma GHR and GH were measured via ELISA. Results: Fasting GH did not differ between groups (mean±SE, CON: 285±78, RnonH: 860±179, PBH: 980±284 pg/mL, P=0.16). Peak incremental glucose response to GCG, ranging from 46-59 mg/dL, did not differ between groups. At 120 min after GCG, GH was significantly higher in both PBH and RnonH vs. CON (PBH: 3018±678, RnonH: 2521±656, CON: 481±137 pg/mL, ANOVA P= 0.012, PBH vs. CON P=0.003, RnonH vs. CON P=0.02). Peak GH in PBH was significantly higher vs. CON (3431± 655 vs. 547±153 pg/mL, P=0.03), but did not differ in RnonH vs. PBH. Peak GH was inversely correlated with postoperative duration in PBH only (r=-0.49, P=0.03), with BMI in both surgical groups (PBH: r=-0.49, P=0.03, RnonH: r=-0.57, P=0.009) and with percent body fat (impedance plethysmography) in the combined surgical group (r=-0.51, P=0.0007). In contrast, GH during hyperinsulinemic hypoglycemia did not differ between groups (CON: 9660 ±2588, RnonH: 7759±1751, PBH: 7309±1549 pg/mL, P=0.3) at similar degrees of hypoglycemia (CON: 54.8±1.5, RnonH: 50.7±1.0, PBH: 50.9±1.4 mg/dL). Fasting plasma GHR did not differ (CON: 23.3±3.8, RnonH: 19.4±2.8, PBH: 13.8±2.1 ng/mL, P=0.10). GHR was correlated with percent fat mass in the combined surgical group (r=0.56, P=0.0003) but not in CON. Conclusion: Plasma GH did not differ as a function of prior RYGB, with or without hypoglycemia, in the fasting state or in response to insulin-induced hypoglycemia. However, GCG-stimulated GH levels were 5-6-fold higher in individuals with history of RYGB, numerically higher in PBH, and inversely related to body fat and postop duration. Together these results suggest that reduced GH is not likely driving hypoglycemia in PBH, but that alterations in glucagon-mediated GH secretion and/or action may contribute to observed metabolic effects of RYGB. Presentation: 6/1/2024

7151 Generation of a Human-Induced Pluripotent Stem Cell Line From a Patient With Hypopituitarism and a Novel Nonsense Variant in FOXA2

Abstract Disclosure: M.A. Camilletti: None. G.T. Chirino Felker: None. G. Amin: None. S. Castañeda: None. F. Zabalegui: None. C. Romano Florit: None. A. Waisman: None. M. Ciaccio: None. M.I. Di Palma: None. E. Vaiani: None. A. Belgorosky: None. S.G. Miriuka: None. L.N. Moro: None. M.I. Perez-Millan: None. Congenital Hypopituitarism (CH) is a genetically complex disease characterized by one or more pituitary hormone deficiencies. Forkhead Box A2 (FOXA2, 600288) is a pioneer transcription factor associated with development of multiple tissues in humans and mice. Heterozygous loss of function mutations in FOXA2 were recently shown to cause CH with hyperinsulinemic hypoglycemia, but little is known about the molecular mechanism of FOXA2 action during pituitary development. We identified a novel, heterozygous nonsense variant in FOXA2 (c.686C&amp;lt;A; p.S229X) in a patient diagnosed with GH deficiency at 1.7 years of age, with anterior lobe hypoplasia and absent pituitary stalk, asymptomatic hypoglycemia, and craniofacial malformations. To discover the mechanism of FOXA2 regulation of pituitary development we generated an induced pluripotent stem cell line (FOXA2mut-iPSC) from the patient’s polymorphonuclear blood cells (PBMCs) using an EF1a-hSTEMCCA-loxP vector containing the pluripotency genes OCT-4, SOX-2, c-MYC and KLF4. FOXA2mut-iPSC clone R1 had a normal karyotype and embryonic stem cell-like morphology. These cells express endogenous pluripotency-associated markers NANOG, SOX2, and OCT4, have alkaline phosphatase activity, and can differentiate into all three developmental layers, indicating that these cells are pluripotent. Short tandem repeat (STR) analysis confirmed that FOXA2mut-iPSC R1 clone profiles matched those of the donor PBMCs. Next, we compared pituitary differentiation of FOXA2mut-iPSC vs. control-iPSCs in vitro. Cells were cultured in a differentiation medium containing BMP4, the smoothened agonist SAG, and fibroblast growth factor (FGF), as described in Zimmer et al., 2016 (1). Gene expression analysis (by qRT-PCR) of samples collected on days 0, 4, 7, and 15 of the differentiation protocol showed an increased expression of genes associated with anterior pituitary development including OTX2, PITX1/2, and SIX1 in both cell lines (n=2). These preliminary data suggest that pituitary cell fate can be induced in the heterozygous FOXA2mut-iPSC clone. Ongoing studies will assess pituitary hormone-producing cell differentiation after longer periods of FOXA2mut-iPSC cell culture. In sum, patient iPSC differentiation is a promising tool for assessment of normal and variant FOXA2 function in human pituitary development, and for enlightening the mechanisms of FOXA2 action in human pituitary development. (1) Zimmer et al., Stem Cell Reports. 2016 Jun 14;6(6):858-872. Presentation: 6/1/2024

8255 Munchausen Syndrome After Partial Pancreatectomy for Insulinoma: A Case Report

Abstract Disclosure: C.R. de Macedo: None. T.D. Bertolacini da Silva: None. I.P. de Magalhães: None. M.A. Pereira: None. I.C. Marques: None. J.L. Pinheiro Filho: None. G.F. Darce: None. D.M. Lourenço Junior: None. Background: Insulinoma is a rare, insulin-secreting pancreatic neuroendocrine tumor, most commonly benign, solitary, sporadic, well differentiated and with a slight female predominance. The investigation of hypoglycemia requires a fasting test to exclude, among other causes, factitious hypoglycemia. Clinical Case: A 27-year-old woman was admitted to the emergency room after seizure by hypoglycemic crisis (capillary blood glucose &amp;lt; 55 mg/dL). She had recurrent episodes of adrenergic/neuroglycopenic symptoms since the age of 14, occurring during fasting, mainly in the morning, with improvement after eating. After confirming Whipple's triad, a fasting test showed hyperinsulinemic hypoglycemia (glycemia 53 mg/dL, normal value &amp;gt;55 mg/dL; insulin 11.5 mcU/mL, nv &amp;lt;3mcU/mL) and increased C-peptide (3.83 ng/mL, nv &amp;lt;0,6 ng/mL). Abdominal magnetic resonance showed a 1.4 cm nodule in the pancreas tail. During hospitalization, she experienced Raynaud's phenomenon, leading to the diagnosis of Raynaud's disease (RD). Distal pancreatectomy was performed, confirming the diagnosis of insulinoma by immunohistochemistry. There was brief remission of the hypoglycemic episodes once they recurred two weeks later. As imaging tests did not show new pancreatic lesions, somatostatin analogue was begun, resulting in improvement for a few more weeks. Due to recurrent hypoglycemia and new seizures, she required continuous intravenous infusion of glucose during hospitalization. A new fasting test revealed hyperinsulinemic hypoglycemia (glycemia 42 mg/dL, insulin 43.3 mcU/mL), low C-peptide (0.5 ng/mL) and normal proinsulin (2.39 pmol/L, nv &amp;lt;5 pmol/L) values. Due RD, auto-immune hypoglycemia was excluded by negative anti-insulin antibodies. Insulinomatosis was also considered, as potential etiology, but review of surgical specimen excluded this hypothesis. After 4 months of hospitalization, due suspicious behavior, a review of her personal belongings revealed insulin vials and needles for injection. The patient confessed to applying insulin to simulate the symptoms, also revealing a history of childhood trauma and previous suicide attempts. After psychiatric evaluation, borderline personality disorder was identified, and Munchausen syndrome was considered. Since then, the patient did not require intravenous glucose with no recurrence of hypoglycemia. Conclusion: The investigation of hypoglycemia can be challenging, requiring appropriate diagnostic protocols. Even in patients who appear to have a well-defined diagnosis, as in our case with anatomopathological confirmation of insulinoma, it is always important to rule out factitious hypoglycemia. The incorrect diagnosis can lead to inappropriate invasive and surgical procedures with definitive consequences, such as exogenous pancreatic insufficiency and insulin-dependent diabetes mellitus. Presentation: 6/1/2024

7799 Nesidioblastosis Concurrent with Anatomically Confirmed Metastatic Gastric Cancer

Abstract Disclosure: Y. Cho: None. K. Jo: None. J. Han: None. S. Moon: None. E. Kim: None. Background: Nesidioblastosis is a rare condition that should be considered in cases of pancreatogenic hyperinsulinemic hypoglycemia without evidence of insulinoma on imaging. We present the first case of nesidioblastosis concomitant with anatomically confirmed metastatic gastric cancer of the pancreas. Case Report A 57-year-old male presented with recurrent episodes of loss of consciousness and hypoglycemia, with a glucose level of 26 mg/dl upon arrival at the emergency room. Despite a history of advanced gastric cancer and previous chemotherapy, the patient had not been diagnosed with diabetes and was not taking medications associated with hypoglycemia. Four months prior, he underwent total gastrectomy. The fasting plasma glucose levels was 38 mg/dl, accompanied by C-peptide levels of 6.10 ng/mL, insulin levels exceeding 1000 uIU/ml, and proinsulin levels at 8.8 pmol/L. The insulin antibody level was more than 100%, and the highest cortisol level reached 15.60 ug/dL during the rapid ACTH stimulation test. The patient's postprandial 2-hour glucose level reached 233 mg/dl during the 75g glucose tolerance test. Imaging studies, including whole-body PET CT and abdominal CT, showed no evidence of suspected metastatic lesions, and the pancreas appeared normal on MRI. Endoscopic ultrasound could not be performed due to anatomical changes following the surgery. A selective arterial calcium stimulation test demonstrated a substantial over twofold increase in insulin concentrations in the gastroduodenal artery, splenic artery, and superior mesenteric artery. The patient received methylprednisolone 125 mg once daily but insulin levels remained elevated, exceeding 1000 uIU/ml, requiring continuous dextrose infusion. Octreotide therapy was initiated, resulting in an improvement in insulin levels to 589 uIU/ml, although discontinuation of dextrose fluid remained unfeasible. After consultation with the surgeon, a open subtotal pancreatectomy was performed, allowing discontinuation of dextrose on the second post-surgery day, with improved glucose and insulin levels. Histological examination showed three clusters of atypical cells with perineural infiltration. Immunostaining indicated negative synaptophysin and positive CK20, suggesting possible gastric cancer metastasis, consistent with prior gastrectomy findings. Moreover, an increased number of variable-sized Langerhans islets exhibited positive insulin and glucagon immunostaining within the islets, indicative of nesidioblastosis. Conclusion: Nesidioblastosis should be considered in cases of unexplained post-surgery hypoglycemia following metastatic gastric cancer treatment. Furthermore, given the potential link with metastatic gastric cancer, which may elude detection via imaging alone, aggressive surgical intervention should be contemplated as a nesidioblastosis treatment strategy. Presentation: 6/3/2024

6981 Atypical hypoglycemia in a teenage boy with prediabetes

Abstract Disclosure: N. Shahid: None. C. salgado: None. N. Gurtunca: None. Background: Hypoglycemia in teenagers is seen less commonly than in younger children. Overweight children with prediabetes presenting with hypoglycemia symptoms are often considered to have reactive post-prandial hypoglycemia due to the degree of hyperinsulinemia with insulin resistance seen in these children. We present a 13-year-old boy with prediabetes, who presented with episodes of altered mental status and was found to have hypoglycemia due to a solitary insulin secreting tumor. Case presentation: A 13-yr old boy with pre-diabetes presented to the ER with altered consciousness and non-ketotic, non-acidotic hypoglycemia [25 mg/dl] &amp; trace ketonuria in the setting of Influenza A infection. Weight and BMI above the 99th%ile and acanthosis nigricans in the skin creases. No access to oral hypoglycemic agents. Urine toxicology was negative. EEG was normal. Euglycemia and level of consciousness restored after IV dextrose &amp; this was considered a possible hypoglycemic seizure episode secondary to poor oral intake. 4 months later he had another episode of altered mental status, jittery movements and was found to be hypoglycemic [41 mg/dl]. He was admitted for further workup of recurrent hypoglycemia. Adrenal insufficiency was ruled out and a diagnostic fast was started. After 15 hours, he developed non-ketotic hypoglycemia [&amp;lt;50 mg/dl]. Critical sample [Table 1] and Glucagon challenge [Table 2] at the termination of the fast confirmed hyperinsulinemic hypoglycemia. Given the unusual age and presentation, an MRI abdomen was done which showed a 1.6 cm lesion in the pancreatic body [Fig 1]. Dotatate whole body PET scan confirmed the insulinoma with no evidence of nodal or distant metastasis [Fig 2]. He underwent surgical enucleation of the insulinoma. Intraoperative secretin showed no evidence of pancreatic duct dilatation or leakage. Hereditary endocrine tumor panel including multiple endocrine neoplasia [MEN] gene analysis was negative. The postoperative course was complicated by a persistent pancreatic leak and pancreatitis eventually requiring an ERCP and stent placement 2 months post operatively. Conclusion: Insulinomas are very rare neuroendocrine tumors in pediatric population, with a prevalence of one in 250,000 and median age at presentation of 45-50 years. About 90% insulinomas are benign and less than 10% are associated with MEN-1 syndrome. Chronic hypoglycemia irrespective of the underlying insulin resistance of prediabetes can be seen with insulinoma and can cause hypoglycemia unawareness as seen in our patient. This has also been reported in literature to be misdiagnosed as refractory epilepsy or psychiatric disorders. Hypoglycemic symptoms at any age should be promptly worked up. Ruling out associated neuroendocrine hereditary tumor syndromes is crucial and prognosis of benign solitary insulinomas after surgical removal is mostly favorable. Presentation: 6/3/2024

8721 A Case of Congenital Hyperinsulinism Manifesting as Transient Hypoglycemia During Illness Due to Mosaic Variant of Unknown Significance in ABCC8

Abstract Disclosure: E.E. Bell-Sambataro: None. L. Mamilly: None. Background: Congenital hyperinsulinism (CHI) is characterized by inappropriate secretion of insulin during periods of low blood glucose. CHI can lead to significant complications such as seizures, developmental delays and neurologic damage. CHI can be caused by multiple genetic variants. The most common genetic etiologies are loss of function mutations in the genes ABCC8 and KCNJ11 encoding the pancreatic Beta (β)-cell ATP-sensitive potassium channel causing over secretion of insulin from the β-cells. We report a challenging pediatric case with a clinical presentation of CHI in an infant with a de novo mosaic ABCC8 gene variant of unknown significance manifesting only during times of illness. Clinical Case: A male infant born at 36 weeks gestational age was transferred to a tertiary center NICU secondary to seizure activity and hypoglycemia after the 24 hours of life with glucose levels as low as 32 mg/dL. His birth weight was normal and there was not maternal history of diabetes mellitus. The hypoglycemia persisted throughout the first week of life and required a glucose infusion rate of 11 mg/kg/min, without success in obtaining a critical sample. He had multiple seizures and MRI brain showed signs of hypoglycemic encephalopathy. Subsequently, he was weaned off IV dextrose and completed a 6 hour safety fast prior to discharge. Rapid genome testing resulted in a de novo, mosaic variant of unknown significance in ABCC8 (C.3622G&amp;gt;A resulting in amino acid substitution p.Glu1208Lys). His family reported significant but transient hypoglycemia during times of illness. At the age of 11 months, he was hospitalized for significant hypoglycemia during an episode of acute gastroenteritis and was treated with dextrose-containing fluids for 36 hours. A subsequent diagnostic fasting study resulted in hypoglycemia within 5.5 hours with capillary glucose of 49 mg/dL. At the time of hypoglycemia, beta hydroxybutyrate was inappropriately low at 0.78 mm, insulin level was suppressed &amp;lt;2 mcIU/mL. Glucagon (30 mcg/Kg) was administered after the initial sample was drawn with a significant increase in glucose from 49 mg/dL to 103 mg/dL. Based on the positive glucagon response and low serum ketone, the clinical diagnosis of CHI was made and diazoxide was initiated while awaiting other results. After the second dose of diazoxide, all glucose levels remained above 80 mg/dL. He was sent home on a continuous glucose monitor and diazoxide. Conclusion: CHI can occur due to autosomal recessive or autosomal dominant ABCC8 loss-of-function mutations of which more than half are not responsive to diazoxide. In this case report, we describe the diagnosis of hyperinsulinemic hypoglycemia in an infant with an ABCC8 variant classified with unknown significance. We describe a good initial response to diazoxide in normalizing blood glucose levels in this infant. Presentation: 6/2/2024

6567 Novel Indication of GLP-1 Receptor Agonists Beyond Weight Loss: Addressing Post-Gastric Bypass Late Dumping Syndrome

Abstract Disclosure: G. Arevalo: None. S. Gra Menendez: None. D. Soliman: None. R.J. Galindo: Consulting Fee; Self; Novo Nordisk, Eli Lilly &amp; Company, Sanofi, Bayer, Inc., Boehringer Ingelheim, Pfizer, Inc., Abbott Laboratories. Grant Recipient; Self; National Institute of Diabetes and Digestive and Kidney Diseases (2P30DK111024), National Institute of Diabetes and Digestive and Kidney Diseases (K23DK123384). Other; Self; Novo Nordisk, Eli Lilly &amp; Company, Dexcom. Background: Late dumping syndrome, characterized by postprandial hyperinsulinemic hypoglycemia (PHH), represents a complex clinical challenge in post-bariatric patients. GLP-1 receptor agonists are being explored as an effective therapeutic option. Clinical Case: A 47-year-old overweight (BMI of 29.86 kg/m²) woman, with a medical history of scleroderma and esophageal dysmotility, underwent a gastric sleeve gastrectomy later requiring conversion to Roux-en-Y gastric bypass to improve esophageal motility. Eleven months post-bypass, she began experiencing recurrent episodes of hypoglycemia (venous glucose 49-70 mg/dL, n &amp;gt;70 mg/dL) accompanied by sweating, palpitations, drowsiness, and weakness. Initial tests were consistent with postprandial hyperinsulinemic hypoglycemia: serum insulin (13.5 µIU/mL, n &amp;lt; 3 µIU/mL), and c-peptide (4.1 ng/mL, n &amp;lt; 0.6 ng/mL). The Sigstad score and the Arts dumping severity score were positive for late dumping syndrome with a score of 26 and 14, respectively. During glucagon administration, the patient's blood glucose level increased by up to 50 mg/dL within 10 minutes of administration. Both sulfonylurea screening and insulin antibody tests were negative. Real-time CGM measurements showed patterns of postprandial hyperglycemic peaks, up to 160-180 mg/dL (n &amp;lt;140 mg/dL), approximately 30 to 60 min after meals, followed by rapidly declining glucose (1-2 hours later), resulting in hypoglycemic events as low as 49 mg/dL. Initial management with dietary changes and pharmacological treatment was unsuccessful due to poor medication tolerability of acarbose and diazoxide, and low adherence to the prescribed diet due to her esophageal dysmotility. The CGM patterns and symptom presentation raised suspicion that late dumping syndrome was triggered by rapid hyperglycemic responses after oral ingestions of typical meals, resulting in the desynchronization of hormonal responses (insulin and GLP-1), and post-prandial hypoglycemia. Hence, the consideration for a GLP-1 receptor agonist emerged. A weekly subcutaneous injection of a long-acting GLP-1 receptor agonist, semaglutide 0.25 mg exhibited marked improvement in her glycemic profile: fewer episodes of postprandial hyperglycemia, and the subsequent descents in blood glucose were less pronounced. The patient demonstrated a favorable response with no severe hypoglycemic episodes reported during a follow-up period of three months. Conclusion: This is the first case to demonstrate semaglutide's efficacy as a standalone treatment for PHH in post-bariatric patients. In this case, semaglutide effectively controlled glycemia and improved the patient's quality of life, presenting a promising therapeutic option for such complex cases. Presentation: 6/1/2024