VIPoma: Clinical manifestations, diagnosis, and management
- Stephen E Goldfinger, MD
Stephen E Goldfinger, MD
- Professor of Medicine
- Harvard Medical School
- Section Editors
- Kenneth K Tanabe, MD
Kenneth K Tanabe, MD
- Section Editor — Gastrointestinal Malignancies
- Professor of Surgery
- Harvard Medical School
- David C Whitcomb, MD, PhD
David C Whitcomb, MD, PhD
- Section Editor — Pancreatic Diseases
- Professor of Medicine
- University of Pittsburgh School of Medicine
VIPomas are rare functioning neuroendocrine tumors that secrete vasoactive intestinal polypeptide (VIP). This topic will review the clinical manifestations, diagnosis, and management of VIPomas. An overview of the clinical manifestations, diagnosis, and management of pancreatic neuroendocrine tumors and other functioning pancreatic neuroendocrine tumors are discussed in detail, separately. (See "Classification, epidemiology, clinical presentation, localization, and staging of pancreatic neuroendocrine tumors (islet-cell tumors)" and "Surgical resection of sporadic pancreatic neuroendocrine tumors" and "Metastatic well-differentiated pancreatic neuroendocrine tumors: Systemic therapy options to control tumor growth and symptoms of hormone hypersecretion" and "Metastatic gastroenteropancreatic neuroendocrine tumors: Local options to control tumor growth and symptoms of hormone hypersecretion" and "Insulinoma" and "Somatostatinoma: Clinical manifestations, diagnosis, and management" and "Glucagonoma and the glucagonoma syndrome" and "Zollinger-Ellison syndrome (gastrinoma): Clinical manifestations and diagnosis" and "Management and prognosis of the Zollinger-Ellison syndrome (gastrinoma)".)
VIPomas are detected in 1 in 10 million people per year . The majority of VIPomas arise within the pancreas, and are classified as functioning pancreatic neuroendocrine (islet cell) tumors. In adults, VIPomas are intrapancreatic in over 95 percent of cases. However, other VIP-secreting tumors have been reported, including lung cancer, colorectal cancer, ganglioneuroblastoma, pheochromocytoma, hepatoma, and adrenal tumors. In children, VIPomas can occur in sympathetic ganglia and the adrenal glands . (See "Classification, epidemiology, clinical presentation, localization, and staging of pancreatic neuroendocrine tumors (islet-cell tumors)", section on 'Classification and nomenclature'.)
VIPomas are usually diagnosed between 30 and 50 years of age in adults and between two and four years of age in children. Symptomatic pancreatic VIPomas are usually solitary, more than 3 cm in diameter, and occur in the tail of the pancreas in 75 percent of patients. Approximately 60 to 80 percent of VIPomas have metastasized by the time of diagnosis [2,3]. VIPomas usually occur as isolated tumors, but in 5 percent of patients they are part of the multiple endocrine neoplasia syndrome type 1 (MEN1) and occur in association with parathyroid and pituitary tumors, gastrinoma, and other tumors . (See "Multiple endocrine neoplasia type 1: Clinical manifestations and diagnosis".)
The VIPoma syndrome is caused by excessive, unregulated secretion of vasoactive intestinal polypeptide (VIP) by the tumor. However, other substances, such as prostaglandin E2, may occasionally be secreted by the tumors . VIP is a 28 amino acid polypeptide that binds to high affinity receptors on intestinal epithelial cells, leading to activation of cellular adenylate cyclase and cAMP production. This results in net fluid and electrolyte secretion into the lumen, resulting in secretory diarrhea and hypokalemia [5,6]. Other biologic actions of VIP including vasodilation, inhibition of gastric acid secretion, bone resorption, and enhanced glycogenolysis are responsible for flushing as well as laboratory findings of hypochlorhydria, hypercalcemia, and hyperglycemia in patients with VIPomas (table 1). (See "Vasoactive intestinal polypeptide" and 'Clinical features' below and "Physiology of gastric acid secretion".)
Clinical manifestations — The majority of patients with VIPoma have VIPoma syndrome, which is also called the pancreatic cholera syndrome, Verner-Morrison syndrome, and the watery diarrhea, hypokalemia, and hypochlorhydria or achlorhydria (WDHA) syndrome. VIPoma syndrome is characterized by watery diarrhea that persists with fasting. Stools are tea-colored and odorless with stool volumes exceeding 700 mL/day. In 70 percent of patients, stool volume can exceed 3000 mL/day [7-9]. Abdominal pain is mild or absent. Associated symptoms include flushing episodes in 20 percent of patients and symptoms related to hypokalemia and dehydration, such as lethargy, nausea, vomiting, muscle weakness, and muscle cramps (table 1). (See "Clinical manifestations and treatment of hypokalemia in adults".)
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- CLINICAL FEATURES
- Clinical manifestations
- Laboratory findings
- DIFFERENTIAL DIAGNOSIS
- TUMOR LOCALIZATION
- Approach to imaging
- Symptomatic treatment
- - Repletion of fluid and electrolytes
- - Somatostatin analogs
- - Glucocorticoids
- Pancreatic resection
- Management of advanced/metastatic disease
- - Liver-directed therapy for metastatic disease
- - Molecularly targeted therapy
- - Cytotoxic chemotherapy
- POST-TREATMENT SURVEILLANCE
- SUMMARY AND RECOMMENDATIONS