VIPoma (Verner-Morrison Syndrome)
Summary
A VIPoma (Vasoactive Intestinal Peptide secreting tumour) is an extremely rare functional Neuroendocrine Tumour (pNET) arising from the pancreatic islet cells. The excess VIP stimulates massive electrolyte and fluid secretion from the small bowel, leading to a life-threatening secretory diarrhoea known as "Pancreatic Cholera". [1,2]
Key Facts
- Incidence: Very rare (1 in 10 million per year).
- Malignancy: 60-80% are metastatic at diagnosis (usually to the Liver).
- Location: 90% are in the Pancreas (Tail > Head). 10% are extra-pancreatic (e.g., Ganglioneuromas in children).
Clinical Pearls
The "WDHA" Syndrome: > 1. Watery Diarrhoea: Voluminous, "tea-coloured", continued even when fasting. > 2. Hypokalaemia: Profound potassium loss in stool, causing weakness and arrhythmia. > 3. Achlorhydria: VIP inhibits Gastrin, leading to low/absent stomach acid.
Secretory vs Osmotic Diarrhoea:
- Osmotic (e.g., Lactose intolerance): Stops when the patient stops eating. Gap between stool osmolality and plasma is high.
- Secretory (e.g., VIPoma, Cholera): Persists during fasting. (The bowel is actively pumping fluid out). Stool osmolality gap is small.
The Flushing Mimic: VIP causes systemic vasodilation. Patients often present with cutaneous flushing, mimicking Carcinoid Syndrome. However, Carcinoid rarely causes hypokalaemia of this magnitude.
Demographics
- Age: Adults 30-50 years.
- Children: Rare, usually ganglioneuromas/neuroblastomas secreting VIP.
- Genetics: less than 5% associated with MEN1 (Multiple Endocrine Neoplasia Type 1).
Mechanism of VIP
- Direct Action: Binds to receptors on intestinal epithelial cells.
- cAMP Activation: Activates Adenylate Cylcase -> increases cAMP.
- Secretion: Drives active secretion of Chloride and Water into the lumen.
- Inhibition: Inhibits absorption of Sodium.
- Result: >3 Litres (sometimes >10L) of fluid loss per day.
- Other Effects: Vasodilation (Flush), Hypercalcaemia (Bone resorption), Glycogenolysis (Hyperglycaemia).
Symptoms
Metabolic Consequences
- General: Signs of severe dehydration (dry mucous membranes, tachycardia, hypotension).
- Abdomen: Usually soft (Tumour is small and retroperitoneal). Hepatomegaly if metastatic.
Biochemistry
- U&E: Low Potassium (often less than 2.5 mmol/L). High Urea/Creatinine.
- Bone: High Calcium (Hypercalcaemia in 50%).
- Glucose: Hyperglycaemia (VIP promotes glycogenolysis).
- Fasting Gut Hormone Screen: Serum VIP > 75 pg/mL (usually >200).
- Must be done while patient is symptomatic (diarrhoeal).
- Requires special Trasylol (aprotinin) tube and rapid freezing.
Stool Analysis
- Stool Volume: >700ml/day (Usually >3000ml).
- Stool Electrolytes: High Sodium and Potassium concentration.
Imaging
- CT Pancreas: Triple phase. Sensitive for pancreatic mass.
- Octreotide Scan / Gallium-68 DOTATATE PET: Gold standard for localising NETs and metastases (as VIPomas express Somatostatin Receptors).
Management Algorithm
SUSPECTED VIPOMA
(Massive Secretory Diarrhoea)
↓
RESUSCITATION (THE PRIORITY)
- IV Fluids (Aggressive)
- IV Potassium / Magnesium
- Correct Acidosis
↓
START SOMATOSTATIN ANALOGUE
- Octreotide / Lanreotide
- Blocks VIP release
- Relief often within hours
↓
CONFIRM DIAGNOSIS & STAGE
- Serum VIP
- CT / DOTATATE PET
↓
┌───────┴───────┐
LOCALISED METASTATIC
↓ ↓
SURGERY DEBULKING
(Resection) + CHEMO / PRRT
(Palliative)
1. Medical (Critical Care)
- Fluid Replacement: May struggle to keep up with losses. Monitor CVP.
- Octreotide: The "magic bullet". Inhibits VIP secretion. Essential for stabilisation before surgery. Controls diarrhoea in >90% of cases.
2. Surgical
- Distal Pancreatectomy / Whipple: Depending on location.
- Cholecystectomy: Usually performed concurrently (as long-term Octreotide causes gallstones).
3. Oncological (Metastatic)
- PRRT (Lutetium-177): For unresectable disease with high receptor uptake.
- Chemotherapy: Streptozocin/5-FU.
- Targeted Therapy: Sunitinib / Everolimus.
- Renal Failure: Acute Tubular Necrosis from shock.
- Cardiac Arrest: From hypokalaemia.
- Octreotide Resistance: Tumours can downregulate receptors over time.
- Resectable: Cure is possible.
- Metastatic: 5-year survival ~60% (Slow growing NETs). Symptom control is the main challenge.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| GEP-NETs | ENETS (European) | Diagnostic criteria and algorithms. DOTATATE PET is standard. |
| Palliative Care | NANETS (USA) | Use of Somatostatin Analogues for symptom control. |
Landmark Evidence
1. Efficacy of Octreotide
- Early trials established that Octreotide reduces VIP levels by >50% and stool volume by >80% within 24-48 hours.
What is a VIPoma?
It is a very rare tumour in the pancreas that produces a hormone called VIP. This hormone tells your bowel to flood with water.
Why is it dangerous?
It acts like Cholera. Your body pumps litres of water and salts (potassium) into your bowel, causing severe diarrhoea. This can dehydrate you rapidly and upset kidney and heart function.
How do we treat it?
First, we replace the fluids and salts. Then we give a drug called Octreotide (an injection) which switches off the hormone production. This stops the diarrhoea almost immediately. Finally, if possible, we operate to remove the tumour.
Primary Sources
- Jensen RT, et al. ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: functional pancreatic endocrine tumor syndromes. Neuroendocrinology. 2012.
- Ito T, et al. Pancreatic neuroendocrine tumors: clinical features, diagnosis and medical management: Update. Curr Opin Endocrinol Diabetes Obes. 2011.
Common Exam Questions
- Syndrome: "WDHA stands for?"
- Answer: Watery Diarrhoea, Hypokalaemia, Achlorhydria.
- Investigation: "Metabolic abnormality?"
- Answer: Hypokalaemia, Hypercalcaemia, Hyperglycaemia.
- Treatment: "Drug to stop diarrhoea?"
- Answer: Octreotide.
- Pharmacology: "Mechanism of diarrhoea?"
- Answer: Secretory (cAMP stimulation).
Viva Points
- Secretory Diarrhoea: How to calculate the stool osmotic gap?
- Gap = 290 - [2 * (Stool Na + Stool K)].
- Osmotic Gap >125 = Osmotic (something is in the bowel holding water).
- Osmotic Gap less than 50 = Secretory (the bowel is secreting water/salt). VIPoma has a LOW gap.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.