SUN-274 A Rare Case of Glucagonoma in a Patient with Multiple Endocrine Neoplasia-Type 1 (MEN1)

Abstract Disclosure: H. El Amri: None. H. Dihowm: None. S. Shannon: None. E. Samoilova: None. A. Swied: None. M.G. Jakoby: None. Introduction: MEN1 is an autosomal dominant disorder caused by mutations in the MEN1 gene that classically manifests as neuroendocrine tumors of the pituitary, parathyroid glands, and pancreas. It is the most important heritable etiology of pancreatic neuroendocrine tumors (pNETs), though glucagonomas in MEN1 are rare. We present a case of glucagonoma in a patient with MEN1. Case: A 70-year-old male was diagnosed with MEN1 at age 62 years after presenting with primary hyperparathyroidism due to two parathyroid adenomas and pNETs. MEN1 missense mutation c.514G>T (p.D172Y) was confirmed. The patient had three pNETs in the head of the pancreas, one in the body, and one in the tail measuring 0.7-1.3 cm in largest diameter and stable in size on annual computed tomography (CT) since initial diagnosis. Historically, he denied symptoms concerning for a functional pNET, and chromogranin A, gastrin, vasoactive intestinal peptide, gastrin, insulin, and glucagon levels were unremarkable on multiple measurements. However, prediabetes was diagnosed on the patient’s most recent yearly evaluation, and two glucagon levels were approximately 2-fold elevated (highest 463 pg/mL, expected < 208). The patient reported borborygmi and mild diarrhea, and a violaceous, plaque-like rash was noted on the forearms and dorsum of both hands. PET dotatate scan demonstrated increased activity localizing to the five pNETs observed on CT and two additional areas in the pancreas, and endoscopic ultrasound guided biopsy of the pNET in the body of the pancreas yielded tissue that stained for glucagon. Treatment with octreotide was started for control of hyperglucagonemia. Conclusion: Glucagonomas are rare pNETs; most are sporadic, though 10-20% occur in cases of MEN1. However, glucagonomas occur in only about 3% of MEN1 cases. Major manifestations of glucagonomas are weight loss, hyperglycemia, necrolytic migratory erythema (NME), and venous thrombosis, and in this patient’s case mild hyperglycemia, rash, and diarrhea were the manifestations at diagnosis. Serum glucagon was < 500 pg/mL and the patient did not have florid glucagonoma syndrome, but this was likely due to early diagnosis as part of annual metabolic and imaging surveillance. The patient’s mutation is located in exon 2 of the MEN1 gene and leads to replacement of aspartic acid with tyrosine at codon 172. This amino acid is highly conserved in vertebrate species, and in silico analysis predicts the mutation to be deleterious. In fact, c.514G>T has been reported in multiple patients with familial and sporadic MEN1, including a patient with an insulinoma. To the best of our knowledge, this is the first case of MEN1 with a glucagonoma caused by the c.514G>T mutation. There are rare cases of MEN1 patients with multiple pNETs and polyhormonal pathology, and this patient is at risk as his mutation is also documented in an insulinoma. Presentation: Sunday, July 13, 2025