Zollinger-Ellison Syndrome
Summary
Zollinger-Ellison Syndrome (ZES) is a clinical syndrome caused by a Gastrinoma—a gastrin-secreting neuroendocrine tumour (NET). The uncontrolled release of gastrin stimulates parietal cells to secrete massive volumes of gastric acid, leading to severe peptic ulcer disease and diarrhoea.
- Sporadic: 75-80%. Usually solitary, potentially curable.
- MEN1 Associated: 20-25%. Multiple Entero-chromaffin-like (ECL) tumours. Harder to cure surgically. [1,2]
Clinical Pearls
The "Paradoxical" Secretin Test: This is the physiological hallmark. In a normal person, giving Secretin inhibits gastrin release. In ZES, the tumour cells are "wired wrong"—giving Secretin causes a massive RISE in gastrin levels.
Location, Location, Location: 90% of Gastrinomas are found in Passaro’s Triangle (Gastrinoma Triangle): > 1. Cystic Duct / CBD junction. > 2. Junction of 2nd/3rd part of Duodenum. > 3. Neck of Pancreas.
Diarrhoea Mechanism: It's not just the ulcers. The sheer volume of acid entering the duodenum overwhelms the bicarbonate buffering capacity. This low pH inactivates pancreatic lipase, leading to fat malabsorption (Steatorrhoea) and secretory diarrhoea.
Demographics
- Incidence: Rare (0.1 to 3 per million).
- Age: 30-50 years.
- Gender: M > F (slightly).
Genetics (MEN1)
- Gene: MEN1 gene (Menin protein) on Chromosome 11q13.
- Inheritance: Autosomal Dominant.
- Screening: Anyone with ZES should be screened for MEN1 (Calcium, PTH, Prolactin).
The Gastrin Axis
- Normal: Antral G-Cells release Gastrin -> Parietal Cells release Acid -> Low pH provides negative feedback to stop Gastrin.
- ZES: Tumour G-Cells release Gastrin autonomously (no negative feedback) -> Parietal Cell Hyperplasia -> Massive Acid Hypersecretion (BAO > 15 mEq/hr).
Symptoms
Signs
- Usually non-specific unless complications (peritonitis from perforation) or MEN1 stigmata present.
Biochemistry
- Fasting Serum Gastrin:
- >1000 pg/mL: Virtuall diagnostic (if pH less than 2).
- 110-1000 pg/mL: Equivocal (seen in PPI use, H. Pylori, Atrophic Gastritis). Needs Secretin test.
- CRITICAL: Must stop PPIs for 1-2 weeks before testing (PPIs raise gastrin).
- Gastric pH: Must be Acidic (pH < 2).
- If Gastrin is high but pH is neutral/high (>4), it is Atrophic Gastritis (Achlorhydria causes reactive gastrin rise), NOT ZES.
- Secretin Stimulation Test:
- Bolus Secretin (2 mcg/kg).
- Positive if Gastrin rises by >120-200 pg/mL.
Imaging (Localisation)
- Somatostatin Receptor Scintigraphy (OctreoScan): Historical standard.
- Gallium-68 DOTATATE PET/CT: Gold Standard. Highly sensitive for NETs.
- Endoscopic Ultrasound (EUS): Best for finding small pancreatic head tumours.
Management Algorithm
SUSPECTED ZES
(Recurrent Ulcers / Diarrhoea)
↓
FASTING GASTRIN + pH CHECK
(Stop PPIs first!)
┌─────────┴─────────┐
GASTRIN HIGH GASTRIN HIGH
pH LOW (less than 2) pH HIGH (>4)
↓ ↓
ZES ACHLORHYDRIA
(Confirm with (Pernicious
Secretin Test) Anaemia)
↓
LOCALISE TUMOUR
(Ga-68 PET / EUS)
↓
TREATMENT
┌─────────┴─────────┐
LOCALISED METASTATIC / MEN1
↓ ↓
SURGICAL MEDICAL
RESECTION - High Dose PPI
(Whipple Procedure - Somatostatin Analogues
or Enucleation) (Octreotide)
Medical
- High Dose PPI: Omeprazole 60mg BD (titrated to keep acid output low). Controls symptoms in almost all patients.
- Octreotide: Somatostatin analogue. Inhibits gastrin release and tumour growth.
Surgical
- Exploratory Laparotomy: Carefully palpate the duodenum/pancreas.
- Resection: Curative in sporadic cases.
- Debulking: In metastatic liver disease.
- Perforation: Multiple ulcers increase perforation risk.
- Oesophageal Stricture: Severe acid reflux.
- Malignancy: 60-90% of Gastrinomas are malignant. They grow slowly but metastasise to liver and bone. Five-year survival is good (80%) even with mets.
- Sporadic: 30-40% cure rate with surgery.
- MEN1: Cure is rare (tumours are multifocal). Management focuses on suppressing acid to prevent ulcers.
- Survival: Generally good (slow growing tumour). 10-year survival >90% if completely resected.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Gastrinoma | ENETS (2016) | Use Gallium-68 PET for localisation. |
| MEN1 | Endocrine Society | Screening protocols for ZES patients. |
Landmark Evidence
1. Berna et al (2006)
- Prospective study showing that "Secretin Test" is the most sensitive and specific provocation test for ZES Diagnosis (Sensitivity 94%).
What is ZES?
It is a rare condition where a small tumour (a "Gastrinoma") produces too much of a hormone called Gastrin. Gastrin's job is to tell your stomach to make acid to digest food. Because the tumour never stops sending the signal, your stomach becomes a factory producing massive amounts of strong acid 24/7.
Why do I have ulcers?
Normally, the stomach has a lining to protect itself, and acid production stops when the stomach is empty. In ZES, the acid levels are so high they burn through the lining of the stomach and the intestine, causing deep ulcers.
Why the diarrhoea?
The acid is so strong it pours into the bowel and destroys the enzymes needed to digest fat. This causes greasy, watery diarrhoea.
Treatment
- Stop the Acid: We give you very high doses of acid-blockers (PPIs). This usually stops the pain and diarrhoea completely.
- Remove the Tumour: If we can find the single knot of cells causing it (using a special scan), a surgeon can remove it and cure you.
Primary Sources
- Jensen RT, et al. ENETS Consensus Guidelines for the Management of Patients with Digestive Neuroendocrine Neoplasms: Gastrinoma. Neuroendocrinology. 2012.
- Berna MJ, et al. A prospective study of gastric acid secretion and gastrin testing in the diagnosis of Zollinger-Ellison syndrome. Ann Surg. 2006.
Common Exam Questions
- Diagnosis: "Multiple jejunal ulcers?"
- Answer: ZES.
- Investigation: "Confirmatory test?"
- Answer: Secretin Stimulation Test.
- Anatomy: "Commonest location?"
- Answer: Duodenum (part of Passaro's Triangle).
- Genetics: "Syndrome associated?"
- Answer: MEN Type 1.
Viva Points
- PPIs and Diagnosis: Always ask if the patient is on a PPI. PPIs raise gastrin levels (because the stomach tries to overcome the drug). This mimics ZES. You must stop the PPI for 2 weeks to get an accurate test.
- Malignancy: Are they benign? No, most are malignant, but they are "indolent" (slow growing).
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.