VIPoma: Watery Diarrhea Syndrome

VIPoma is a rare neuroendocrine tumor, most commonly arising from pancreatic islet cells (90% in the pancreatic body/tail), that secretes excessive vasoactive intestinal peptide (VIP), producing the classic WDHA syndrome: Watery Diarrhea, Hypokalemia, and Achlorhydria (also called Verner-Morrison syndrome or pancreatic cholera). VIP is a 28-amino-acid neuropeptide that acts on intestinal epithelial cells via VPAC receptors to stimulate massive secretion of water and electrolytes into the intestinal lumen while simultaneously inhibiting gastric acid secretion (achlorhydria). The secretory diarrhea is characteristically large-volume (>3 liters/day, often 5-10 L/day), watery, tea-colored, odorless, and persists during fasting -- distinguishing it from osmotic diarrhea. The diarrhea is isotonic and rich in potassium and bicarbonate, causing profound hypokalemia (leading to muscle weakness, cardiac arrhythmias, ileus) and metabolic acidosis (non-anion gap from bicarbonate loss). VIP also causes vasodilation producing episodic flushing, and inhibits gastric acid production causing achlorhydria/hypochlorhydria. Additional metabolic derangements include hyperglycemia (VIP stimulates glycogenolysis) and hypercalcemia (in ~50% of cases, from bone resorption or co-secretion of PTHrP). Diagnosis requires demonstrating elevated fasting plasma VIP levels (>75 pg/mL, often >200 pg/mL) in the setting of secretory...