Conditions · Gastroenterology and hepatology

Zollinger-Ellison syndrome (gastrinoma) !

A gastrin-making tumour, usually in the pancreas or duodenum, drives huge stomach acid output, causing severe, repeated ulcers and diarrhoea.

Updated 2026-11-01

Structures involved

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Why it happens

What it is

A syndrome caused by a gastrin-secreting neuroendocrine tumour (gastrinoma), usually in the duodenum or pancreas. The excess gastrin causes marked acid hypersecretion with severe, multiple or atypical peptic ulcers, reflux and diarrhoea.

Who gets it

Rare; it accounts for a very small fraction of peptic ulcer disease. Most cases are sporadic, and about a quarter occur as part of multiple endocrine neoplasia type 1 (MEN1). Diagnosis is often delayed for years because acid-suppressing drugs mask symptoms.

Causes

Gastrinoma: a neuroendocrine tumour that secretes gastrin
Most arise in the 'gastrinoma triangle', in the duodenal wall or the head of the pancreas
Sporadic tumours, or inherited as part of MEN1 (MEN1 gene)
More than half are malignant, spreading to lymph nodes and liver

Risk factors

Multiple endocrine neoplasia type 1 (with hyperparathyroidism and pituitary tumours)
Family history of MEN1

Pathophysiology

Gastrin from the tumour stimulates parietal cells and their growth, so the stomach secretes very large amounts of acid. The acid overwhelms duodenal neutralisation, causing multiple ulcers, including in unusual sites such as the distal duodenum and jejunum. Acid in the small bowel inactivates pancreatic lipase and damages the mucosa, causing diarrhoea and fat malabsorption. Gastrin also thickens the gastric folds.

Classification

Sporadic gastrinoma (most cases), often single
MEN1-associated gastrinoma, usually multiple small duodenal tumours
Localised versus metastatic (lymph nodes, liver)

Symptoms and signs

Burning epigastric pain from peptic ulcers that are severe, multiple or recurrent
Chronic watery or fatty diarrhoea that improves with acid suppression
Severe gastro-oesophageal reflux
Nausea, vomiting and weight loss
Ulcers in atypical places (beyond the duodenal bulb, jejunum) or without Helicobacter pylori or NSAID use

Diagnosis

Clinical: Suspected with refractory, multiple or atypical ulcers, ulcers without H. pylori or NSAIDs, ulcers with diarrhoea, prominent gastric folds, or a personal or family history of MEN1.
Tests: Fasting serum gastrin is markedly raised while gastric pH is acidic (acid-suppressing drugs must be stopped carefully under supervision, since they also raise gastrin). A secretin stimulation test shows a paradoxical rise in gastrin. Serum calcium and parathyroid hormone screen for MEN1; chromogranin A may be raised.
Imaging: Upper endoscopy shows ulcers and thick gastric folds. Tumour localisation with contrast CT or MRI, somatostatin receptor imaging (gallium-68 DOTATATE PET/CT) and endoscopic ultrasound.

Differential diagnosis

Common peptic ulcer disease from Helicobacter pylori or NSAIDs
Other causes of high gastrin with low acid: atrophic gastritis, pernicious anaemia, acid-suppressing drugs
Gastric outlet obstruction or G-cell hyperplasia
Other causes of chronic diarrhoea (VIPoma, celiac disease, inflammatory bowel disease)

Goal of treatment

Control acid secretion to heal ulcers and prevent complications, then remove the tumour when possible and treat metastatic disease.

Treatment

Medical: High-dose proton pump inhibitors are the mainstay to control acid, heal ulcers and stop diarrhoea; somatostatin analogues for metastatic or unresectable tumours.
Surgical: Surgical exploration and removal of a localised sporadic gastrinoma can be curative; in MEN1 the decision is individualised, and parathyroid surgery for hyperparathyroidism is done first because high calcium increases gastrin.
Medical: For advanced disease: targeted therapies, chemotherapy, liver-directed treatments or peptide receptor radionuclide therapy.
Follow-up: Follow-up of gastrin levels, symptoms and imaging for recurrence; screening for other MEN1 tumours and genetic testing of relatives when MEN1 is present.

Drugs for this condition

Complications

Ulcer bleeding, perforation and gastric outlet obstruction
Oesophagitis and oesophageal stricture
Malabsorption and weight loss
Liver metastases
Vitamin B12 deficiency with long-term acid suppression

Prognosis

Good when the tumour is localised and resected, and acid can usually be controlled with drugs. Survival depends mainly on the presence of liver metastases.

Test yourself

Think of the answer, then tap the question to see it.

Where is the 'gastrinoma triangle'?

The area bounded by the cystic duct–common bile duct junction, the junction of the second and third parts of the duodenum, and the neck–body junction of the pancreas; most gastrinomas lie in the duodenum or pancreatic head.

Which test shows a paradoxical rise in gastrin in Zollinger-Ellison syndrome?

The secretin stimulation test.

Which inherited syndrome is associated with gastrinoma?

Multiple endocrine neoplasia type 1 (parathyroid, pituitary and pancreatic tumours).

Why does Zollinger-Ellison syndrome cause diarrhoea?

Excess acid in the small bowel damages the mucosa and inactivates pancreatic enzymes, causing secretory and fatty diarrhoea.

What is the first-line drug class for controlling acid in gastrinoma?

Proton pump inhibitors, at high doses.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: Zollinger-Ellison syndrome: MedlinePlus Medical Encyclopedia (MedlinePlus (U.S. National Library of Medicine), 2025).

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Pancreas highlighted on the Durgical 3D model