(WDHA, acronym for Watery Diarrhea, Hypokalemia, Achlorhydria)

(formely: Verner-Morrison syndrome)

Estimated incidence of 1/107 per year. It is a tumor secreting the Vasoactive Intestinal Peptide (VIP) that produces a syndrome  associating refractory watery diarrhea, hypokaliemia, achlorhydria and an endocrine tumor of the pancreas. This tumor, originating from the pancreatic islets also secretes the histidine methionine peptide, but only VIP is the cause of the symptoms. The location of the tumor is generally pancreatic (85-95 %), with a predominance in the caudal region; rare cases of VIPoma are secondary to a carcinoid tumor, a pheochromocytoma, a ganglioneuroma or a ganglioneuroblastoma. In children, a VIPoma can develop in neural crest-derived tumors such as the neuroblastoma, the localization of which is in the adrenal gland in 38 % of cases. A distinction is made between the primary forms, which appear before the tumor is known or allow its diagnosis, and the secondary forms that appear during the treatment of a neuroblastoma and are of worse prognosis. A neuroblastoma producing VIP often secretes large amounts of catecholamines even if no signs of systemic hypertension are observed.

In adults, the mass is often greater than 3 cm in diameter and solitary. The tumor is malignant in 80 % of cases. In 60-80 % of cases, there are metastases at the time of diagnosis; however, the 5-year survival rate is 50 to 70 %.

The VIP is a hormone of 28 amino acids found in different tissues: central and peripheric nervous system, heart, lungs, urinary and intestinal tract. Its mode of action is not fully understood to date; two receptors called VPAC1 and VPAC2 are at the origin of the bioactivity of the VIP. These receptors are found on many cells, including cells of the immune system.

The main symptoms are

-        massive and prolonged watery diarrhea (volume of stools when fasting > 750 to 1000 mL/day and non-fasting > 3000 mL/day)

-        symptoms of hypokaliemia, metabolic acidosis and dehydration. In half of the patients, diarrhea is constant; the severity of diarrhea varies over time. About 33 % of patients have diarrhea 1 year before the diagnosis, among which 25 % had diarrhea for more than 5 years before. Other common signs include drowsiness, muscle weakness, nausea, vomiting and abdominal pain. During diarrheal episodes, 20 % of patients experience hot flashes such as in carcinoid syndrome

As fecal water and electrolyte loss increases once rehydration is achieved, the continuous IV replacement can become difficult.

Octreotide is usually used to control diarrhea, but high dosages are required. Surgical resection is curative in 50 % of patients with localized tumors. New chemotherapy for VIPoma includes protocols based on everolimus, or sunitinib. Chemotherapy is not curative.

Anesthetic implications:

check volemia and blood electrolytes  in the presence of signs of carcinoid syndrome (see this term); implications of associated pathologies. In case of neuroblastoma, check for possible  associated secretion of catecholamines by the tumor.

References : 

-        Bourgois B, Boman F, Nelken B, Bonnevalle M, Turck D.
Diarrhée profuse révélatrice d’une neuroblastome hypersécrétant le vasoactive intestinal peptide.
Arch Pédiatr 2004 ; 11 : 340-3.

-        De Carli E, Timsit S, Coze C, Chastagner P, Rubie H et al.
Neuroblastomes sécrétant du VIP. SFCE-P32.
Arch Pédiatr 2008 ; 15 : 1016

Updated: January 2020