2026-06-24 | Near-Total Pancreatectomy for Congenital Hyperinsulinemic Hypoglycemia: A Single-Center Experience From a Low-Resource Setting in Sudan

Background and objective Congenital hyperinsulinemic hypoglycemia (CHH) is the leading cause of persistent hypoglycemia in neonates and infants. In high-resource settings, diagnosis and management depend on rapid genetic testing and advanced imaging to differentiate focal from diffuse disease. However, in low-resource settings, limited diagnostic capacity and lack of access to medications often necessitate early surgical intervention. This study aimed to evaluate the clinical features, surgical intervention, and outcomes in infants undergoing pancreatectomy for congenital hyperinsulinism at Al Ribat University Hospital, Sudan. Methods A retrospective descriptive study was conducted, involving all pediatric patients who underwent pancreatectomy for CHH from January 2019 to December 2024. Data were extracted from operative logs and medical records, including demographics, diagnostic investigations, medical therapy, surgical procedures, postoperative complications, histopathology, and one-year outcomes. Descriptive statistics and appropriate inferential statistical tests were used for the analysis. Results Thirty-two patients were included, of whom 19 (59.4%) were female. The majority were diagnosed during the first week of life (n = 19, 59.4%). Diazoxide was administered to 30 (93.75%) patients, with only eight (26.7%) showing a therapeutic response. Restricted access to genetic testing (n = 8, 25%) and imaging (n = 6, 18.8%) resulted in the predominance of near-total pancreatectomy (n = 31, 96.9%). Intraoperative complications were minimal, with bleeding occurring in two cases (6.25%) and vascular injury in one case (3.1%). Early postoperative hypoglycemia was noted in 13 patients (40.6%), whereas hyperglycemia was noted in one patient (3.1%). Surgical complications included wound infection in seven patients (21.9%) and intestinal obstruction in one patient (3.1%). Histopathology confirmed CHH in all cases, with diffuse disease in 27 patients (84.4%). During a one-year follow-up period, three patients (9.4%) died, including two (6.3%) due to recurrent hypoglycemia. Conclusions Near-total pancreatectomy remains a practical and life-saving option for infants with medically unresponsive CHH in low-resource settings where diagnostic and pharmacologic limitations restrict individualized care. Despite limited access to preoperative localization and the predominance of diffuse disease, surgical outcomes were acceptable, with low intraoperative morbidity and manageable rates of postoperative complications. Persistent postoperative hypoglycemia and late mortality highlight the need for structured endocrine follow-up and improved access to medical therapy. Strengthening diagnostic capacity, ensuring medication availability, and establishing coordinated multidisciplinary care pathways are essential to improving long-term outcomes for children with CHH in resource-limited environments.

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2026-06-10 | Structural basis of insulin receptor antagonism by bivalent site 1-site 2 ligands S961 and Ins-AC-S2.

Congenital hyperinsulinism is a rare genetic disease characterized by overproduction of insulin. One class of potential treatments is insulin receptor antagonists like S961 and Ins-AC-S2, which comprise segments for binding each of the two insulin-binding sites (site 1 and site 2) on the receptor. Notably, S597 - containing the same receptor binding segments as S961 but in the opposite order (site 2-site 1) - is an insulin receptor agonist rather than an antagonist. Using cryo-EM, we show how both S961 and Ins-AC-S2 bind an inactive conformation of the receptor, thereby explaining their antagonism. Furthermore, our structures reveal how agonist vs. antagonist activity is influenced by the order of site 1- and site 2-binding modules in bivalent ligands. Additionally, we show subtle differences between the receptor-binding mechanisms of S961 and Ins-AC-S2, which include displacement or engagement of αCT, and a binding interface between the Ins-AC-S2 insulin and the receptor FnIII-2/insert domains. These structural insights may inform development of next generation insulin receptor antagonists for treatment of congenital hyperinsulinism.

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2026-06-01 | Beyond BRUE (Brief Resolved Unexplained Event): Recurrent Unexplained Events Revealing Congenital Hyperinsulinism in Infancy.

Brief resolved unexplained events (BRUEs) are uncommon yet clinically significant presentations in infancy that require careful risk stratification, as recurrent episodes may herald serious occult pathology. We report a four-month-old term female infant with a notable family history of sudden unexplained sibling deaths who was admitted to and later discharged from our institution twice for recurrent BRUE episodes following an initially unrevealing workup. She subsequently presented again with vomiting, diarrhea, dehydration, metabolic acidosis, and persistent hypoglycemia, necessitating admission to the pediatric intensive care unit (PICU).  During PICU admission, the infant developed recurrent hypoglycemia despite escalating intravenous glucose infusion rates (GIRs). Critical sampling demonstrated inappropriately detectable insulin and C-peptide, absent ketonuria, suppressed β-hydroxybutyrate, and a diagnostically significant glycemic response to glucagon, confirming hyperinsulinemic hypoglycemia (HH) consistent with congenital hyperinsulinism (CHI). She responded promptly to diazoxide and hydrochlorothiazide, allowing successful weaning from intravenous glucose and transition to full oral feeds. This case compellingly demonstrates how seemingly benign recurrent BRUE episodes may, in fact, constitute the earliest clinical clue to a serious yet treatable occult disorder.

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