Zollinger–Ellison syndrome

Signs and symptoms

Patients may experience abdominal pain and diarrhea. Chronic diarrhea, including steatorrhea, can occur. Pain in the esophagus, especially between and after meals at night, nausea, wheezing, vomiting blood, malnourishment, loss of appetite, and malabsorption are possible.

Untreated, the condition can lead to severe gastroesophageal reflux disease and refractory peptic ulcer disease. About one-half to two-thirds of single gastrinomas are malignant, often spreading to the liver and lymph nodes near the pancreas and small bowel. Nearly 25% of patients have multiple tumors as part of MEN 1, which also involves tumors in the pituitary and parathyroid glands.

Pathophysiology

Gastrin acts on parietal cells of the gastric glands, causing them to secrete more hydrogen ions into the stomach lumen and acting as a trophic factor that leads to parietal cell hyperplasia. Normally, hydrogen ion secretion is controlled by a negative feedback loop, but the neuroendocrine tumor in Zollinger–Ellison syndrome has no regulation, resulting in excessively large amounts of secretion. The increase in acidity contributes to peptic ulcers in the stomach, duodenum, and occasionally the jejunum, the last being an atypical ulcer.

Diagnosis

The syndrome may be suspected when symptoms resist treatment, are especially suggestive, or when endoscopy is suggestive. Diagnosis involves several tests: a secretin stimulation test, which measures evoked gastrin levels (gastrinoma cells release gastrin in response to secretin, unlike normal physiology); fasting gastrin levels on at least three occasions; measurement of gastric acid secretion and pH; and an increased level of chromogranin A, a marker of neuroendocrine tumors. The source of increased gastrin is determined using MRI or somatostatin receptor scintigraphy. Diagnosis can be difficult in patients taking proton pump inhibitors, which inadvertently increase gastrin production and may cause false positives even weeks after stopping the medication.

Did You Know?

• Proton pump inhibitors and histamine H2-receptor antagonists are used to slow acid secretion.
• Robert M. Zollinger and Edwin H. Ellison first postulated a causal relationship between pancreatic tumors and peptic ulceration.