What is a VIPoma?

A VIPoma is a rare pancreatic neuroendocrine tumor (NET) that secretes excessive vasoactive intestinal peptide (VIP), causing severe, watery diarrhea, electrolyte abnormalities, and dehydration. The syndrome is also called WDHA syndrome (Watery Diarrhea, Hypokalemia, Achlorhydria) or Verner-Morrison Syndrome.

Key Facts:

• Extremely Rare: ~1 in 10 million per year
• Location: Pancreas (90%)—usually body or tail; also adrenal, retroperitoneum
• Malignant in 40-70%: Metastases (liver, lymph nodes) at diagnosis in ~50%
• Peak Age: 40-60 years (adults); rare pediatric cases (often ganglioneuromas/ganglioneuroblastomas)

How Does High VIP Cause Symptoms?

• VIP (Vasoactive Intestinal Peptide): Gut hormone that relaxes smooth muscle, stimulates intestinal secretion
• Excessive VIP → Massive Fluid/Electrolyte Secretion into Gut:
  • Profuse watery diarrhea (secretory)
  • Dehydration
  • Electrolyte losses (potassium, bicarbonate)
  • Gastric acid suppression (achlorhydria)

Classic Syndrome (WDHA):

• Watery Diarrhea (100%)
• Hypokalemia (low potassium) (80-100%)
• Achlorhydria (low/absent gastric acid) (70-80%)
• Often includes Dehydration and Acidosis

Symptoms:

1. Secretory Diarrhea (100% - HALLMARK):

• Massive Volume: >3 liters/day (often 5-10 liters/day)
• Watery, Rice-Water Appearance
• Secretory: Persists with fasting (doesn't improve when you stop eating)
• Chronic, Relentless

2. Severe Dehydration:

• Thirst, dry mucous membranes
• Hypotension (low blood pressure)
• Prerenal kidney failure

3. Hypokalemia (Low Potassium):

• From massive stool losses
• Symptoms: Muscle weakness, cramping, fatigue, cardiac arrhythmias
• Can be life-threatening

4. Metabolic Acidosis:

• Loss of bicarbonate in stool

5. Other Symptoms:

• Flushing (20-30%): From VIP vasodilation
• Hyperglycemia (50%): VIP stimulates glycogenolysis
• Hypercalcemia (25-50%)
• Weight Loss
• Abdominal Cramping

Diagnosis:

1. Stool Output:

• Measure 24-hour stool volume (>3 liters/day strongly suggestive)
• Secretory Diarrhea: Continues with fasting (unlike osmotic diarrhea)

2. Serum VIP:

• Normal: <75-190 pg/mL
• VIPoma: Markedly elevated (typically >500-1000 pg/mL)
• Diagnostic Test

3. Labs:

• Hypokalemia: Potassium often <2.5 mmol/L
• Metabolic Acidosis: Low bicarbonate
• Hypercalcemia (Check Calcium)
• Hyperglycemia (Check Glucose)
• Gastric pH Analysis: Achlorhydria (high pH >7)
• Chromogranin A: Tumor marker (elevated)

4. Imaging (Localize Tumor, Assess Metastases):

• CT or MRI Abdomen: Identify primary tumor (often large), liver mets
• Gallium-68 DOTATATE PET/CT: Somatostatin receptor imaging
• Endoscopic Ultrasound (EUS): Visualize pancreatic tumor

Treatment:

1. Fluid and Electrolyte Replacement (IMMEDIATELY):

• IV Fluids: Normal saline, balanced crystalloids (massive fluid losses)
• Potassium Replacement: Aggressive IV and oral potassium (often requires >100-200 mEq/day)
• Bicarbonate: If severe acidosis
• Ongoing Replacement: Match output (can require several liters/day)

2. Somatostatin Analogs (SSAs) - FIRST-LINE for Symptom Control:

• Octreotide (Sandostatin®), Lanreotide (Somatuline®)
• Effects:
  • Inhibit VIP secretion
  • Dramatically reduce diarrhea (often >90% reduction in stool volume)
  • Normalize electrolytes
  • Slow tumor growth
• Dosing: Often start with subcutaneous octreotide 100-200 mcg 3x/day, then transition to long-acting monthly injections
• Very Effective—most patients achieve excellent symptom control

3. Surgery (If Resectable):

• Tumor Resection: Potentially curative if all tumor removed
• Debulking Surgery: Even if metastatic—reduces VIP production, improves symptoms
• Cure Rate: ~30-50% (many have metastases at diagnosis)

4. For Metastatic/Unresectable Disease:

• Peptide Receptor Radionuclide Therapy (PRRT): Lutetium-177 DOTATATE (Lutathera®)
• Everolimus (Afinitor®): mTOR inhibitor; slows tumor progression
• Chemotherapy: Streptozocin-based regimens (modest efficacy)
• Liver-Directed Therapies: Embolization, RFA for liver mets

5. Supportive Treatment:

• Antidiarrheal Agents: Loperamide (modest benefit)
• Nutritional Support: Oral rehydration solutions, electrolyte-rich fluids

Differential Diagnosis of Secretory Diarrhea:

• Carcinoid syndrome (also NETs, but produce serotonin)
• ZES (gastrinoma)—acid-induced diarrhea
• Cholera
• Laxative abuse
• Villous adenoma (colon)

Prognosis:

• Slow-Growing Tumors
• 5-Year Survival:
  • Localized: 50-70%
  • Metastatic: 30-60%
• Somatostatin analogs provide excellent symptom control, greatly improving quality of life
• Many patients live for years even with metastatic disease