Zollinger-Ellison Syndrome

Definition

Zollinger-Ellison Syndrome (ZES) is a rare disorder characterized by gastrin-secreting tumors (gastrinomas), usually in the pancreas or duodenum, leading to gastric acid hypersecretion and recurrent peptic ulcers.

Epidemiology

• Incidence: ~1–3 cases per million per year
• Accounts for <1% of peptic ulcer disease cases
• Mean age at diagnosis: 40–50 years
• Slight male predominance
• About 20–25% of cases are associated with Multiple Endocrine Neoplasia type 1 (MEN1)
• Gastrinomas are malignant in ~60–90% of cases, often with liver metastases at diagnosis

Etiology

• Sporadic gastrin-secreting tumors of the pancreas or duodenum (majority)
• MEN1 syndrome: autosomal dominant disorder involving parathyroid, pituitary, and pancreatic tumors
• Rarely, gastrinomas may arise in other locations (stomach, lymph nodes)
• Genetic mutations in MEN1 gene lead to tumor development
• Hypergastrinemia drives excessive gastric acid production

Pathophysiology

• Gastrinomas produce excess gastrin → stimulates parietal cells → increased gastric acid secretion
• Hyperacidic stomach environment leads to recurrent peptic ulcers, often multiple and distal (jejunal ulcers)
• Excess acid may cause diarrhea due to inactivation of pancreatic enzymes and mucosal injury
• Acid hypersecretion can lead to gastroesophageal reflux disease (GERD)
• Tumor may metastasize, commonly to the liver, increasing morbidity and mortality
• Association with MEN1 may lead to additional endocrine tumors (parathyroid hyperplasia, pituitary adenomas)