Endocrine Atlas

Gastrinoma (Zollinger-Ellison Syndrome)

What is Gastrinoma/Zollinger-Ellison Syndrome?

A gastrinoma is a rare neuroendocrine tumor that secretes excessive gastrin, causing severe peptic ulcer disease and diarrhea. The clinical syndrome it produces is called Zollinger-Ellison Syndrome (ZES).

Key Facts:

  • Incidence: 0.5-2 cases per million per year (very rare)
  • Location:
    • Duodenum (50-70%)—most common
    • Pancreas (20-40%)
    • Called the "gastrinoma triangle" (duodenum, pancreas head, lymph nodes)
    • Rare: Stomach, liver, ovary
  • Malignant in 50-60%: Higher than insulinoma
  • Associated with MEN1: 20-25% of gastrinomas occur in MEN1 syndrome
  • Peak Age: 40-60 years

How Does High Gastrin Cause Symptoms?

  • Gastrin: Hormone that stimulates stomach acid (HCl) production
  • Excessive Gastrin → Excessive Acid → Multiple Problems:
    • Severe, recurrent peptic ulcers (stomach, duodenum)
    • Esophagitis, GERD
    • Diarrhea (acid damages small intestine, inactivates digestive enzymes)

Symptoms:

  • Peptic Ulcer Disease (75-90%):
    • Severe, recurrent ulcers
    • Multiple ulcers
    • Ulcers in unusual locations (beyond first part of duodenum, jejunum)
    • Refractory to standard treatment
    • Abdominal pain, nausea
  • Diarrhea (50-75%): Watery, high-volume
  • GERD/Esophagitis: Severe heartburn, difficulty swallowing
  • Complications:
    • GI bleeding (from ulcers)
    • Perforation
    • Strictures (scarring from chronic ulcers)

When to Suspect Gastrinoma:

  • Recurrent or refractory peptic ulcers
  • Multiple ulcers or ulcers in unusual locations
  • Ulcers + diarrhea
  • Strong family history of peptic ulcers or MEN1
  • Ulcers in young patients without H. pylori or NSAID use

Diagnosis:

1. Fasting Serum Gastrin:

  • Normal: <100 pg/mL
  • Gastrinoma: Typically >1000 pg/mL (very high gastrin is highly suggestive)
  • If 100-1000 pg/mL: Indeterminate; proceed to secretin stimulation test
  • Important: Stop PPIs 1-2 weeks before testing (PPIs raise gastrin); can use H2-blockers instead

2. Gastric pH (Gastric Acid Analysis):

  • Gastric pH <2:< /strong> Confirms high acid production (rules out achlorhydria as cause of high gastrin)

3. Secretin Stimulation Test:

  • If fasting gastrin equivocal (100-1000 pg/mL)
  • Give IV secretin; measure gastrin at 0, 2, 5, 10, 15, 20 minutes
  • Positive: Gastrin rises >120 pg/mL (paradoxical rise—normally secretin suppresses gastrin)

4. Imaging (Localize Tumor):

  • CT or MRI Abdomen: Identify primary tumor, metastases
  • Endoscopic Ultrasound (EUS): Sensitive for small pancreatic/duodenal tumors
  • Somatostatin Receptor Imaging: Gallium-68 DOTATATE PET/CT or octreotide scan
  • Note: Gastrinomas are often small and difficult to localize

5. Rule Out Other Causes of High Gastrin:

  • PPI Use: Most common cause of elevated gastrin (2-4x normal)
  • Chronic Atrophic Gastritis: Low acid → high gastrin (gastric pH >3)
  • H. pylori Infection
  • Chronic Kidney Disease
  • Pernicious Anemia

Treatment:

1. High-Dose Proton Pump Inhibitors (PPIs) - ESSENTIAL:

  • Omeprazole, Lansoprazole, Esomeprazole
  • Dose: Much higher than standard (e.g., omeprazole 60-120 mg/day or more)
  • Goal: Control acid secretion → heal ulcers, resolve diarrhea
  • Lifelong therapy if tumor cannot be resected

2. Surgery (If Localized, Non-Metastatic):

  • Tumor Resection: Potentially curative if all tumor removed
  • Duodenotomy with Tumor Excision: For duodenal gastrinomas
  • Pancreatic Resection: For pancreatic gastrinomas
  • Lymph Node Dissection: High rate of lymph node involvement
  • Cure Rate: ~30-40% (many have occult metastases at diagnosis)

3. For Metastatic/Unresectable Tumors:

  • Somatostatin Analogs (Octreotide, Lanreotide): Reduce gastrin secretion, slow tumor growth
  • Peptide Receptor Radionuclide Therapy (PRRT): Lutetium-177 DOTATATE
  • Everolimus (mTOR Inhibitor): Slows tumor progression
  • Chemotherapy: Streptozocin-based regimens
  • Liver-Directed Therapies: For liver metastases (embolization, RFA)

Association with MEN1:

  • 20-25% of gastrinomas occur in MEN1 syndrome
  • MEN1 gastrinomas:
    • Often multiple, small duodenal tumors
    • Younger age
    • More difficult to cure surgically
  • Screen for MEN1 if: Family history, young patient, other endocrine tumors (parathyroid, pituitary)

Prognosis:

  • Slow-Growing Tumors: Even metastatic disease progresses slowly
  • 5-Year Survival:
    • Localized: >95%
    • Metastatic: 50-70%
  • Prognosis improved dramatically with PPIs (before PPIs, complications from ulcers were leading cause of death)

Key Points:

  • Gastrinoma = tumor secreting excessive gastrin → severe peptic ulcer disease + diarrhea
  • Zollinger-Ellison Syndrome = clinical syndrome from gastrinoma
  • Diagnosis: Elevated fasting gastrin (>1000 pg/mL) + high gastric acid
  • Treatment: High-dose PPIs (essential for symptom control); surgery if resectable
  • 50-60% malignant; metastases common but slow-growing
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