7940 Insulinoma as a Rare Manifestation of MEN4

Abstract Disclosure: H. Han: None. J. Moalem: None. A.R. Shih: None. B.J. Gigliotti: None. Background/Objective: Multiple endocrine neoplasia 4 (MEN4) is a rare syndrome that is caused by germline mutations in CKDN1B. Its phenotypic expression is similar to multiple endocrine neoplasia 1 (MEN1). Manifestations include primary hyperparathyroidism (PHPT), pituitary adenomas, and pancreatic neuroendocrine tumors (NET). Prevalence of MEN4 is less than one per million. Case Report: A 55-year-old female with history of hypercalcemia presented with symptomatic hypoglycemia. She had a fasting plasma glucose of 41mg/dL, proinsulin of 84.3 pmol/L, insulin level of 24 uIU/mL, c-peptide of 5.2 ng/mL, and beta hydroxybutyrate level of 0.34 mmol/L, consistent with endogenous hyperinsulinism. She was incidentally noted to have PHPT. CT abdomen showed a 1.5 x 1.1 x 1.0 cm pancreatic lesion consistent with an insulinoma. Pathology from subsequent Whipple surgery showed that it was a well-differentiated neuroendocrine tumor with no metastasis. She became normoglycemic after surgery. Germline testing revealed a variant of unknown significance in CDKN1B (p.R93W). Discussion: Increasing evidence suggests that MEN4 exhibits subtle differences in penetrance and natural history compared to MEN1. A recent systemic review of MEN4 cases showed that most gastrointestinal NETs in MEN4 are non-functional NETs and gastrinomas; to date, no insulinomas have been reported. PHPT in MEN4 may exhibit a lower risk of recurrence after parathyroidectomy. This case highlights the importance of germline genetic testing when a patient presents with clinical manifestations of MEN1. Conclusion: This is the first reported case of insulinoma in MEN4. Presentation: 6/3/2024