VIP

**Physiology** - Vasoactive intestinal peptide is a 28-amino-acid peptide in the secretin/glucagon family. It is made by enteric neurons (submucosal and myenteric plexuses), the hypothalamus (suprachiasmatic nucleus), and pancreatic islet cells. - It acts through Gs-coupled receptors (VPAC1/VPAC2), which raise cAMP. - Effects: - Increases intestinal secretion of water and electrolytes (Cl⁻ and HCO3⁻ secretion). - Relaxes smooth muscle, including the lower esophageal sphincter, gallbladder, and intestinal and vascular smooth muscle. This causes vasodilation. - Inhibits gastric acid secretion, causing hypochlorhydria or achlorhydria. - Stimulates pancreatic bicarbonate secretion. - It is released from neurons in response to distention and vagal stimulation. - It is a co-transmitter with NO in the enteric nervous system. It mediates the receptive relaxation reflex and the descending relaxation of peristalsis. - Low or absent VIP and NO neurons at the lower esophageal sphincter cause achalasia. In Hirschsprung disease, the aganglionic segment lacks VIP/NO neurons and stays constricted.

**VIPoma (Verner-Morrison syndrome, WDHA syndrome, pancreatic cholera)** - Cause: a non-α, non-β islet cell tumor, usually in the pancreatic tail. It can also arise in neural tissue, such as neuroblastoma or ganglioneuroma in children. It is associated with MEN1. - Presentation: Watery Diarrhea, Hypokalemia, Achlorhydria. This is the WDHA mnemonic. Other findings are non-anion-gap metabolic acidosis from stool bicarbonate loss, flushing, hypercalcemia, and hyperglycemia. - The diarrhea is a large-volume secretory diarrhea (>3 L/day). It persists with fasting and the stool osmotic gap is low. - Diagnosis: elevated fasting serum VIP, then CT or MRI, or somatostatin receptor scintigraphy (octreotide scan). - Treatment: - Correct fluid and electrolyte losses. - Give octreotide (a somatostatin analog) to control symptoms. - Resect the tumor surgically.

**Other uses of "VIP" (for context)** - VIP is not the same as "VIPoma"-related terms such as "VIP" in cardiology. Know it is also sometimes used for the **VIP (vasoactive intestinal peptide) in cluster/trigeminal autonomic cephalalgias**, where it is elevated during attacks and mediates parasympathetic lacrimation and rhinorrhea. - VIP is also a parasympathetic co-transmitter in salivary glands. It causes vasodilation and increases the gland's secretory response.

**Boards pearls** - Think VIPoma when you see secretory watery diarrhea with hypokalemia and achlorhydria and no response to fasting. - Key distinctions among pancreatic neuroendocrine tumors: - Gastrinoma (Zollinger-Ellison): ↑ gastrin, peptic ulcers, steatorrhea. - Somatostatinoma: diabetes, steatorrhea, gallstones. - Glucagonoma: necrolytic migratory erythema, diabetes, weight loss. - Insulinoma: Whipple triad. - Contrast with VIP on gastric acid: gastrin increases acid secretion, but VIP, somatostatin, and secretin decrease it.