Diagnosis

VIPoma

Etiology

Cause [w89]

• Neuroendocrine Islet cell tumors associated with multiple endocrine neoplasia type 1

  • Insulinoma

  • Gastrinoma

  • ACTHoma

  • VIPoma

Anatomic localisation [bag][qbr]

• Pancreas: 95%

• Non-pancreatic tissue: colon, liver and neural crest-derived tissues

• Metastases: liver, lymph nodes, bones, and kidney

Pathophysiology [qbr]

1. VIP is a neurohormone produced by the neurons in the CNS, GI, respiratory, and urogenital tracts

2. VIP effects:

   • Vasodilator

   • Decreased smooth muscle activity --> decreases GI motility

   • Stimulate water and electrolyte secretion from the intestinal tract

   • Inhibit gastric acid secretion

   • Increase blood flow mainly in the GI tract

   • Promote glycogenolysis, lipolysis, and bone resorption

3. VIPoma are usually malignant and can metastasize to the liver and lymph nodes

4. Clinical manifestations: 

   • WDHA syndrome: Watery Diarrhea, Hypokalemia, Achlorhydia/hypochhlorhydia

   • Dehydration

   • Muscle weakness (electrolyte imbalance)

   • Metabolic acidosis

Complications [qbr]

• Excessive VIP: Dehydration, hypokalemia, metabolic acidosis, renal failure, malnutrition

• Thromboembolic events

• Metastasis

• Treatment: surgical and medical complications

Epidemiology

Incidence per 100.000 [e4b][7g2][soe][bag][qbr]

Approach

• Clinical suspicion: large volume secretory diarrhea (usually >3 L per day, no osmolar gap in the stool fluid) [rk2]

  (WDHA syndrome: Watery Diarrhea, Hypokalemia, Achlorhydria)

• Blood test: elevated VIP levels >250 pg/mL, hypokalemia, hyperglycemia, hypercalcemia and non-anion gap metabolic acidosis [bag][qbr]

• CT abdomen

• MRI abdomen

• Somatostatin receptor scintigraphy (Octreoscan)

• Endoscopic ultrasound

• Biopsy with immunohistochemical stains

Treatment

1. Initial treatment: [bag][qbr][rk2]

   • Replace the massive loss of fluids: intravenous fluid

   • Restore electrolyte levels: potassium replacement

   • Reverse acidosis

2. Control diarrhea:

   • Octreotide (a somatostatin analogue) to reduce VIP hormone levels: 50 - 100 ug subcutaneously every 8 hours and titrated for symptom control

   • Long-acting somatostatin analogues

   • Glucocorticoids are used in patients refractory to somatostatin analogs

   • Interferon-alpha if treatment resistent disease

   • Loperamide

3. Surgical resection if primary cancer and/or limited liver metastases

   • Liver transplantation is a potential treatment for highly selected patients

4. If unresectable metastatic disease:

   • Radiofrequency ablation and cryoablation if diameter <3 cm

   • Hepatic artery embolization - a palliative treatment if unresectable liver metastases

   • Chemotherapy (docorubicin/streptozocin)

Differential diagnoses

Amyotrophic lateral sclerosis, Bile acid malabsorption, Carcinoid syndrome, Celiac disease, Cholera, Clostridium tetani, Crohn disease, Gastroenteritis, HIV, Hyperkalemia, Hyperphosphatemia, Hyperventilation, Hypocalcemia, Hypocapnia, Hypokalemia, Hypomagnesemia, Hypoparathyroidism, Infectious colitis, Milk-alkali syndrome, Short bowel syndrome, Tropical sprue, Ulcerative colitis, Zollinger-Ellison syndrome