VIPoma

Overview

VIPoma is a rare type of neuroendocrine tumor that secretes excessive amounts of vasoactive intestinal peptide (VIP), leading to a distinct clinical syndrome known as WDHA syndrome (Watery Diarrhea, Hypokalemia, and Achlorhydria). Most VIPomas originate in the pancreas, particularly in the tail, but they can also occur in other parts of the gastrointestinal tract or even in extra-abdominal sites. These tumors are typically malignant and may metastasize, most commonly to the liver. VIPoma is most often diagnosed in adults, with a peak incidence between 30 and 50 years of age.

Causes

VIPomas arise from the neuroendocrine cells that produce VIP, a peptide hormone that regulates water and electrolyte secretion in the intestines. The exact cause of VIPoma is unknown, but several factors may contribute:

• Sporadic mutations: Most cases are sporadic with no identifiable inherited component

• Genetic syndromes: Rarely associated with Multiple Endocrine Neoplasia type 1 (MEN1)

• Pancreatic neuroendocrine neoplasia: VIPomas are a subtype of these rare tumors

Symptoms

The hallmark symptoms of VIPoma are related to the overproduction of VIP, which leads to excessive secretion of water and electrolytes in the intestines. Common clinical features include:

• Profuse, watery diarrhea: Often persistent and can lead to dehydration

• Hypokalemia: Low potassium levels causing muscle weakness, cramps, and cardiac arrhythmias

• Achlorhydria or hypochlorhydria: Decreased stomach acid production

• Flushing, nausea, vomiting, and abdominal cramps

• Weight loss due to malabsorption and fluid loss

• Fatigue and generalized weakness

Diagnosis

Diagnosis of VIPoma involves a combination of clinical suspicion, laboratory tests, and imaging studies. The key steps include:

• Serum VIP levels: Markedly elevated levels (>75 pg/mL) are diagnostic

• Electrolyte panel: Reveals hypokalemia and metabolic acidosis

• Stool analysis: Confirms secretory diarrhea with high sodium and chloride content

• Imaging studies: CT scan or MRI to identify pancreatic or metastatic tumors

• Somatostatin receptor scintigraphy (Octreoscan): Useful for detecting primary and metastatic lesions

• Endoscopic ultrasound (EUS): May aid in localization of pancreatic tumors

Treatment

Treatment of VIPoma involves controlling symptoms and removing or reducing tumor burden. Management strategies include:

• Somatostatin analogs (e.g., octreotide, lanreotide): To inhibit VIP secretion and control diarrhea

• Fluid and electrolyte replacement: To correct dehydration and hypokalemia

• Surgical resection: Preferred for localized tumors, offering the best chance for cure

• Chemotherapy: For metastatic or unresectable tumors (e.g., streptozocin, fluorouracil, or temozolomide-based regimens)

• Targeted therapies: Everolimus and sunitinib may be used in progressive cases

• Liver-directed therapies: Embolization or radiofrequency ablation for liver metastases

Prognosis

The prognosis of VIPoma depends on the stage at diagnosis and the tumor’s response to treatment. Localized tumors that are surgically resectable have a favorable outcome, with long-term survival possible. However, most cases are diagnosed at an advanced stage with metastases, particularly to the liver, which can reduce survival. With advances in symptom control and targeted therapies, the quality of life and survival of patients with metastatic VIPoma have improved significantly. Ongoing monitoring is essential for managing recurrence and complications.