SUN-022 Severe Secretory Diarrhea With Mildly Elevated VIP Levels From A Pancreatic Neuroendocrine Tumor Without VIP Expression In A Patient With Prior Prolactinoma

Abstract Disclosure: F. Abdo: None. L. Sayyed Kassem: None. Pancreatic neuroendocrine tumors (pNETs) are rare, and vasoactive intestinal peptide-secreting tumors (VIPomas) are among the least common functional subtypes. We present the case of a 75-year-old male with a background of prolactinoma on cabergoline therapy who developed progressively worsening diarrhea over two years. His symptoms, initially attributed to irritable bowel syndrome with diarrhea (IBS-D) and recurrent infections, escalated to multiple hospitalizations for refractory nausea, vomiting, diarrhea, and severe electrolyte disturbances, culminating in hypovolemic shock and requiring intensive care unit (ICU) management. Testing confirmed that the diarrhea was secretory in nature. During hospitalization, capsule endoscopy revealed mucosal inflammation and ulcerations without bleeding. Workup demonstrated markedly elevated chromogranin A (2,853 ng/mL), mildly elevated plasma VIP (85.7 pg/mL, repeated: 22.9, ULN 58.8), and fasting gastrin levels peaking at 1,875 pg/mL while on high doses of proton pump inhibitors (PPI). 24-hour urinary 5-HIAA and thyroid-stimulating hormone (TSH) were within normal limits. PET Cu-64 dotatate imaging showed a somatostatin receptor-avid lesion near the pancreatic head and multiple areas of increased uptake in the pancreas. Endoscopic ultrasound (EUS) with fine-needle aspiration confirmed a low-grade, well-differentiated pNET. Given the finding of pancreatic NET and prolactinoma, the patient was evaluated for MEN1including parathyroid hormone (PTH) and calcitonin levels, both within normal limits. Genetic testing for MEN1 returned negative. The patient was started on monthly long-acting octreotide with resolution of diarrhea and improvement in electrolytes; however, he was readmitted for hypokalemia and hypomagnesemia despite continued absence of diarrhea. Further testing ruled out mineralocorticoid excess. He underwent distal pancreatectomy, lymph node dissection, and cholecystectomy. Pathology confirmed a 3 cm pancreatic head mass with low-grade pNET (Ki-67 <3%) staining negative for VIP and positive for synaptophysin, CD56, CDX2, and MOC-31. An additional 0.8 cm focus in the posterior pancreatic body and a positive lymph node were identified as well. Octreotide was discontinued postoperatively without recurrence of diarrhea and with marked reduction of chromogranin A to 483 ng/ml while on PPI 1 month postoperatively. This case highlights the diagnostic complexity of functional neuroendocrine tumors presenting with chronic secretory diarrhea Despite negative immunostaining for VIP, the combination of his clinical presentation, biochemical testing, imaging and surgical pathology point to a functional pNET. Whether this represents a case of VIPoma with episodic secretion and therefore only mildly elevated VIP levels, or a pNET secreting a non-evaluated gastrointestinal peptide, is unclear. Presentation: Sunday, July 13, 2025