Verner-Morrison Syndrome

A very rare syndrome caused by tumoral-inappropriate vasoactive intestinal peptide secretion. Can be associated with multiple endocrine neoplasias. Clinical aspect is a result of intensive diarrhea that can lead to dehydration and severe hypokalemia.

WDHA Syndrome; Water Diarrhea, Hypokalemia, Achlorhydria Syndrome; WDHH Syndrome; Water Diarrhea, Hypokalemia, Hypochlorhydria Syndrome; Diarrheagenic Syndrome; Pancreatic Cholera; Vipoma Syndrome.

Described by John U. Verner and Ashton B. Morrison, both American physicians, in 1958.

3:10,000,000 people in the general population.

This disease is caused by inappropriate secretion of vasoactive intestinal peptide (VIP), usually secreted from non-beta islet pancreatic cells in response to food containing fat, proteins, and alcohol. It relaxes smooth muscles, resulting in a decrease of lower esophageal sphincter pressure, relaxation of the gastric antrum and body, and inhibition of gallbladder and intestinal circular muscle contraction. Extra secretion of VIP will provide general manifestations such as vasodilatation, positive inotropic action on the heart, increase in intestinal water and electrolyte secretion, inhibition of gastrin and gastric acid secretion, and stimulation of pancreatic secretion.

Characterized by severe watery diarrhea and dehydration. Diagnosis is confirmed by biochemistry (hypokalemia, hypochloremia, metabolic acidosis, high plasma VIP levels; approximately two-thirds of patients have hypercalcemia and 50% are hyperglycemic), stool analysis (isotonic, alkaline, cultures negative), and ultrasonography and CT imaging (dilated gallbladder, localization of tumors). Prostaglandin E and E2 hypersecretion can be associated.

Hypermotility, watery diarrhea syndromes with hypokalemia and hypochloremia or hyperchloremia, dehydration. Lethargy, muscular weakness, nausea, vomiting, and abdominal pain are frequent. Fluid secretion may exceed 3 to 5 L, with a loss of 200 to 300 mEq of potassium daily. Some cases of VIPoma have included hypercalcemia, flushing, and glucose intolerance. Ectopic primary sites, such as the liver and jejunum, occur in approximately 10% of patients. In children, the VIPoma syndrome is caused by either a ganglioneuroma or ganglioneuroblastoma. In adults, it is caused by bronchiogenic carcinoma, pheochromocytoma, medullar thyroid carcinoma, and retroperitoneal histiocytoma. Multiple endocrine neoplasia type 1 can be associated (in MEN, hypercalcemia is frequent).

Evaluate the extent of the diarrhea (history, clinical repercussion, laboratory investigations including natremia, kalemia, calcemia, urea, creatinine, glycemia, arterial blood gas analysis). Also, the tumor repercussion must be assessed because of the risk of obstruction of the duodenum or of the biliary tract and of vascular erosion (radiography, CT, endoscopy). Preoperative ECG should be done in cases of hypokalemia. Evaluate existence and repercussion of flushing episodes (history, clinical, heart rate and blood pressure measurement during flush).

Preoperative hydration and electrolyte correction is necessary based on the laboratory investigations. Elective surgical procedures must be postponed until electrolytes and the intravascular fluid status have been corrected. Vascular access can be extremely difficult and an emergency route may be used (intraosseous, superior longitudinal sinus). Central venous access using Seldinger technique should be avoided in cases of hypokalemia and cardiac irritability. Glucose levels should be regularly evaluated and fluid regimen adapted. Perioperative blood pressure and cardiac monitoring should be performed. Normocapnic ventilation is recommended to avoid respiratory alkalosis in cases of severe hypokalemia. Removal of tumor will provide fast resolution of symptoms.

Medullar regional anesthesia should probably be avoided because of the risk of potentialization of the vasoplegic effects of VIP release. Muscle relaxants are not contraindicated but their action can be prolonged in presence of uncorrected hypokalemia (monitoring is necessary).

Other pancreatic endocrine tumors. Clinical features vary based on secretion: insulinoma (insulin); Zollinger-Ellison syndrome (gastrin); glucagonoma (glucagon); Cushing syndrome (adrenocorticotropic hormone); mild hyperglycemia with cholelithiasis (somatostatin).