Zollinger-Ellison syndrome

Zollinger-Ellison syndrome (ZES) is a rare disorder characterized by the formation of one or more gastrinomas, which are gastrin-secreting tumors typically located in the pancreas or duodenum. These tumors lead to excessive secretion of gastric acid, resulting in severe peptic ulcers, chronic diarrhea, and other gastrointestinal complications.

Pathophysiology

Zollinger-Ellison syndrome is caused by gastrin-secreting tumors (gastrinomas) that lead to excessive stimulation of the parietal cells in the stomach. This results in:

• Increased gastric acid secretion – Leading to ulcer formation.
• Hypertrophy of gastric mucosa – Due to prolonged stimulation by gastrin.
• Malabsorption and diarrhea – Caused by acid-induced inactivation of pancreatic enzymes.

Gastrinomas are often malignant, with potential to metastasize, most commonly to the liver and lymph nodes. Approximately 25% of cases are associated with [[Multiple endocrine neoplasia type 1 or (MEN1), a genetic disorder affecting endocrine glands.

Clinical Presentation

Symptoms of Zollinger-Ellison syndrome result from excessive gastric acid production and may include:

• Recurrent peptic ulcers – Often multiple and located in unusual sites such as the jejunum.
• Severe abdominal pain – Due to ulceration and inflammation.
• Gastroesophageal reflux disease or (GERD) – Persistent acid reflux symptoms.
• Chronic diarrhea – Resulting from acid-induced malabsorption.
• Weight loss – Due to malnutrition and chronic diarrhea.
• Nausea and vomiting – In severe cases, especially with gastric outlet obstruction.

Diagnosis

The diagnosis of Zollinger-Ellison syndrome is based on clinical suspicion and biochemical testing:

• Serum gastrin levels – Markedly elevated (>1000 pg/mL) in fasting conditions.
• Secretin stimulation test – A paradoxical rise in gastrin confirms diagnosis.
• Gastric pH measurement – pH <2 suggests excessive acid production.
• Imaging studies:
• Endoscopic ultrasound (EUS) – To locate small tumors.
• CT or MRI scans – To detect metastatic spread.
• Somatostatin receptor scintigraphy – Identifies gastrinomas via receptor binding.

Treatment

The management of Zollinger-Ellison syndrome involves acid suppression and tumor control.

Acid Suppression

To prevent ulcer complications and alleviate symptoms:

• Proton pump inhibitors (PPIs) – Such as omeprazole and pantoprazole are first-line therapy.
• H2 receptor blockers – Such as ranitidine (less commonly used).

Tumor Control

For localized or metastatic gastrinomas:

• Surgical resection – If tumors are localized and operable.
• Somatostatin analogs – Such as octreotide for symptom control.
• Chemotherapy – For advanced, metastatic disease.
• Targeted therapies – Investigational treatments for MEN1-associated gastrinomas.

Prognosis

The prognosis of Zollinger-Ellison syndrome depends on:

• Extent of disease – Localized gastrinomas have a better prognosis.
• Presence of metastasis – Especially to the liver, which worsens outcomes.
• Response to therapy – Effective acid suppression improves quality of life.

Patients with MEN1-related ZES require lifelong monitoring due to the potential development of multiple endocrine tumors.

Related Pages

• Gastrinoma
• Peptic ulcer disease
• Multiple endocrine neoplasia type 1
• Proton pump inhibitors
• Hypergastrinemia