Zollinger-Ellison Syndrome - Gastrinoma

Zollinger-Ellison Syndrome - Gastrinoma

 

Zollinger-Ellison syndrome (ZES) is a type of pancreatic neuroendocrine tumor (PNET) and is characterized by refractory peptic ulcer disease, diarrhea and gastric acid hypersecretion as a result of an islet cell tumor of the pancreas (gastrinoma).

Epidemiology

  • Incidence – 1/1,000,000
  • Age – diagnosis usually made between ages of 30 and 50 years
  • Sex – nearly equal in males and females
  • Occurrence – sporadic, although 20-30% are genetic

Inheritance

  • MEN 1 (Wermer syndrome)
    • Parathyroid gland hyperplasia or tumor, endocrine tumor of the pancreas or duodenum and pituitary gland
    • Autosomal dominant trait

Pathophysiology

  • Islet cell tumor which secretes gastrin
  • Gastrin stimulates parietal gastric cells to grow in number
  • Increased number of parietal cells increases the basal and maximal acid secretion
  • Increased acid secretion leads to ulcers and diarrhea
  • Most (≥80%) tumors occur in the duodenum and in the head of the pancreas
  • Frequently, multiple tumors are present
  • Approximately 50% are malignant and metastasize

Clinical Presentation

  • Abdominal pain with peptic ulcer disease
    • Multiple ulcers common
    • Ulcers are refractory to therapy
  • Gastroesophageal reflux and possibly esophageal stenosis or Barrett mucosa
  • Diarrhea – caused by acid secretion that inactivates pancreatic lipase and bile salts
  • Hypercalcemia – if associated with MEN 1
  • Metastatic disease – most often hepatic

Diagnosis

  • Indications for testing – refractory peptic ulcer disease, multiple peptic ulcers, familial peptic ulcer disease, peptic ulcer disease with diarrhea
  • Laboratory testing
    • Gastrin, serum fasting – >200 pg/mL
    • Gastric acid analysis – increased BAO >15 mEq (mmol/L)/hr or >5 mEq (mmol/L)/hr after acid reducing surgery
    • Secretin stimulation test
      • Not recommended for patients with acute pancreatitis
      • Avoid effects on gastrin release
        • Fasting on the day of study
        • Acid suppressive medications discontinued well in advance
      • Baseline blood samples
        • Taken 5 minutes and immediately prior to secretin administration [Note:  not currently available]
      • Administration of pure porcine secretin (2 units/kg) IV
        • Given over a 30-second time period
      • Serum samples
        • Initial samples at 2 and 5 minutes post injection
        • Additional samples every 5 minutes for 20 minutes
      • Positive secretin stimulation test (increase in serum gastrin by more than 200 pg/mL) may confirm presence of gastrinoma
  • Imaging studies
    • CT scan
    • MRI and scintigraphy with somatostatin receptors
  • Histological studies
    • Final confirmation of tumor type – special stains may be required

Differential diagnosis

  • Helicobacter pylori infection
  • Gastric outlet obstruction
  • Pernicious anemia
  • Gastroesophageal reflux disease
  • Peptic ulcer disease
  • Short bowel syndrome

Treatment

  • Control gastric acid hypersecretion
  • Control tumor growth

See Also