The syndrome of watery diarrhea, hypokalemia, and achlorhydria (ie, WDHA syndrome) is a rare condition characterized by severe, watery diarrhea resulting from the oversecretion of vasoactive intestinal peptide (VIP) from non–beta pancreatic islet cells.
Patients usually have elevated VIP levels and have a history of frequent hospitalizations for dehydration and/or hypokalemia. Because this condition resembles cholera, Matsumoto and colleagues (1966) suggested the alternative term pancreatic cholera. (See Etiology, Presentation, Treatment, and Medication.)
A small percentage of patients with WDHA syndrome also have hypercalcemia, hyperglycemia, hypochlorhydria, and flushing. Multiple endocrine neoplasia type 1 (MEN-1) syndrome (ie, Wermer syndrome) is present in a very small subset of patients with hypercalcemia and WDHA syndrome. (See Etiology.)
VIP-secreting tumors are rare, affecting 0.05-0.2 per million adults, and these tumors most often originate in the pancreas (approximately 80%). With these pancreatic primaries, around 50% have metastasized at the time of diagnosis of the tumor. Other ectopic primary sites of VIP production include the liver and jejunum in about 10% of patients with WDHA syndrome, and, on occasion, other tumors can deteriorate into VIP-producing tumors (eg, phaeochromocytomas
). In children, the VIPoma syndrome is caused by either a ganglioneuroma or ganglioneuroblastoma.
The goals of therapy are prolongation of life, control of symptoms, and correction of the electrolyte abnormalities. Surgical resection offers the only chance for cure, but the tumor not uncommonly has spread to regional lymph nodes and/or to the liver at the time of diagnosis. Palliative treatment consists of surgical resection of the primary tumor with regional lymph node dissection and, if possible, resection of hepatic metastases. Liver transplantation has been performed in and uncontrolled manner, and results appear to demonstrate a potential role, although the scarcity of the resource limits this modality’s availability.
When managed medically, the use of somatostatin analogs has become the mainstay of therapy for symptom control. Other palliative measures include systemic chemotherapy, hepatic arterial embolization with or without chemotherapy, and the use of interferon alfa. (See Treatment, and Medication.)
In contrast to pancreatic carcinoma treatment, an aggressive surgical approach in WDHA syndrome appears warranted in light of improved 5-year survival rates with palliative debulking of tumors. Selected patients with extensive hepatic metastases have been treated with orthotopic liver transplantation with excellent results, although experience remains limited.
Complications of WDHA syndrome may include the following:
Acute renal failure associated with hypokalemia – This is the most common cause of death in WDHA syndrome; the typical renal lesion observed in these patients is a vacuolar tubular nephropathy
Non–anion gap metabolic acidosis
Perianal skin irritation from severe diarrhea
Poor quality of life from severe diarrhea
Patients should be advised to seek treatment at a center with expertise in this field. Patients need to be aware that dehydration and acute renal failure are significant complications and that they must seek hospitalization if they are not doing well at home.