Zollinger-Ellison syndrome

Zollinger-Ellison Syndrome (ZES):

1. Pathophysiology

• Zollinger-Ellison syndrome is caused by a gastrinoma, a neuroendocrine tumor that secretes excessive gastrin, leading to hypersecretion of gastric acid.
• The excessive acid causes peptic ulcers, gastroesophageal reflux disease (GERD), and diarrhea due to acid inactivation of digestive enzymes.

2. Causes & Associations

• Sporadic cases: Most occur as isolated tumors.
• Multiple Endocrine Neoplasia type 1 (MEN1): About 25% of cases are associated with MEN1, an inherited disorder that affects multiple endocrine glands.

3. Symptoms

• Severe, recurrent peptic ulcers (duodenal and gastric).
• Chronic diarrhea (due to excess acid reaching the intestines).
• Heartburn and reflux (due to excessive acid production).
• Abdominal pain (often mistaken for common peptic ulcer disease).

4. Diagnosis

• Serum gastrin levels: Markedly elevated (>1000 pg/mL, often >10 times normal).
• Secretin stimulation test: Used if gastrin levels are borderline; a paradoxical increase in gastrin confirms ZES.
• Imaging: CT scan, MRI, or somatostatin receptor PET/CT to locate the tumor.
• Endoscopy: May show multiple ulcers, hypertrophic gastric folds, and erosions.

5. Treatment

• Proton pump inhibitors (PPIs): Omeprazole, pantoprazole, or esomeprazole to reduce acid production.
• Somatostatin analogs (e.g., octreotide) in metastatic cases.
• Surgical resection: If the tumor is localized, surgery is the best option for cure.
• Chemotherapy: Used in metastatic or unresectable cases (e.g., streptozocin, 5-fluorouracil).
• Targeted therapies: Everolimus or sunitinib for advanced neuroendocrine tumors.

6. Prognosis

• Localized gastrinomas: Good prognosis with surgery.
• Metastatic cases (especially to the liver): Poorer prognosis but can be managed with medical therapy.
• MEN1-associated ZES: Typically requires lifelong management due to multiple tumors.