Zollinger-Ellison Syndrome

Description

• Zollinger-Ellison syndrome (ZES) triad
  • Markedly elevated gastric acid secretion
  • Peptic ulcer disease
  • A gastrinoma or non-β islet cell tumor of the pancreas or duodenal wall that produces gastrin (hypergastrinemia)
    • Gastrinomas (at the time of diagnosis) may be single or multiple (1/2 to 2/3), large or small, benign or malignant (2/3), sporadic (70–75%) or associated with multiple endocrine neoplasia type 1 (MEN1) (25–30%).
• System(s) affected: endocrine/metabolic, gastrointestinal
• Synonym(s): Z-E syndrome; pancreatic ulcerogenic tumor syndrome; multiple endocrine neoplasia, partial; ulcerogenic islet cell tumor

Epidemiology

Incidence

• 1 to 3 per million per year in the United States
• Predominant age: middle age (30 to 65 years). Mean age of onset is 43 years; presents a decade earlier in patients with ZES/MEN1
• Predominant sex: male > female (1.3:1)

Pediatric Considerations
Aggressive cases have been reported in teenagers.

Pregnancy Considerations
Rare, pregnancy alters medication choices and surgical timing.

Etiology and Pathophysiology

• Gastrinoma is found the head of the pancreas (20–30%) and the first or second portion of the duodenum (70–80%); if in the pancreas, the lesion is more likely to metastasize to the liver.
• Hypergastrinemia results in gastric mucosal hypertrophy and increased acid production. Increased acid production causes mucosal ulceration. Diarrhea (60%) and malabsorption are also common in ZES.
• Increasing number found in stomach wall, up to 8%; may be due to increased surveillance and/or increased PPI use masking symptoms
• Also may be found rarely in the mesentery, peritoneum, spleen, skin, or mediastinum (possibly metastasis with primary not identified)

Genetics

• ~25–30% of cases occur in association with the autosomal dominant MEN1 syndrome—tumors of pancreas, pituitary, and parathyroid.
• Can occur sporadically as well

Risk Factors

• MEN1
• Family history of ulcer disease

General Prevention

Screen first-degree relatives of patients with MEN1.

Commonly Associated Conditions

• MEN1
• Insulinoma
• Carcinoid tumors