MON-022 Rare, Meet Rarer: Insulinoma Found in MEN Type 4

Abstract Disclosure: K. Akella: None. A.C. Zuzek: None. Y. Dai: None. Introduction: Insulinoma, a rare pancreatic neuroendocrine tumor, is a source of increased endogenous insulin production that causes hypoglycemia. It is associated with genetic disorders, including Multiple endocrine neoplasia type 1 (MEN1). Its evidence in Multiple endocrine neoplasia type 4 (MEN4) has only been recently established. This case highlights a patient with insulinoma-induced recurrent hypoglycemia associated with MEN4 syndrome. Case Description: A 39-year-old male with no significant family history presented to the hospital with recurrent, progressive episodes of severe hypoglycemia over five months. The initial workup revealed a blood glucose level of 46 mg/dL (70-100 mg/dL), proinsulin level of 11.4 pmol/L (0.0-10.0 pmol/L), insulin level of 3.28 uIU/mL (3.20-16.3 uIU/mL), c-peptide level of 0.88 ng/mL (0.8-4.20 ng/mL), and a beta-hydroxybutyrate concentration of 0.08 mmol/L (0.02-0.27 mmol/L). The urine sulfonylurea screen was negative. A computed tomography (CT) scan of the abdomen and pelvis with intravenous contrast raised concerns for two tumors: one located in the pancreatic body/tail and another in the uncinate process/duodenal wall. An endoscopic ultrasound confirmed the presence of a hypoechoic mass in the pancreatic body/tail, with fine needle aspiration pathology confirming a neuroendocrine tumor. The insulinoma in the pancreatic tail was successfully enucleated, and laparoscopic examination did not reveal any lesions in the uncinate process. Hypoglycemia did not recur after the surgery. Genetic testing later identified a heterozygous c.429delG mutation in the CDKN1B gene. Of note, an MRI of the head with and without contrast to rule out pituitary lesions was negative and laboratory studies ruling out other lesions did not indicate hyperparathyroidism or abnormalities in pituitary hormone levels. Discussion: MEN4 is a rare disorder associated with mutations in CKDN1B gene. The syndrome most commonly affects the parathyroid, pituitary glands, and gastrointestinal tract. Only one reported insulinoma was previously in patients with MEN4. In this case, only the pancreas was affected, whereas the pancreas and parathyroid were affected in the first published report. Presentation: Monday, July 14, 2025