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BASICS

  • Definition: Triad of
  • Markedly elevated gastric acid secretion
  • Peptic ulcer disease
  • Gastrinoma (gastrin-secreting tumor of pancreas or duodenal wall) causing hypergastrinemia
  • Gastrinomas can be single/multiple (50%-66%), benign or malignant (~66%), sporadic (70-75%) or MEN1-associated (25-30%)
  • Synonyms: Z-E syndrome; pancreatic ulcerogenic tumor syndrome

EPIDEMIOLOGY

  • Incidence: 1 to 3 per million per year (US)
  • Age: Mean onset 43 years; MEN1 patients present ~10 years earlier
  • Sex: Male > Female (1.3:1)
  • Pediatric: Aggressive cases reported in teenagers
  • Pregnancy: Rare; affects medication choice and surgery timing

ETIOLOGY AND PATHOPHYSIOLOGY

  • Gastrinoma locations:
  • Duodenal wall: 70-80% (more common)
  • Pancreatic head: 20-30% (more likely to metastasize to liver)
  • Hypergastrinemia → gastric mucosal hypertrophy → increased acid → mucosal ulceration
  • Diarrhea and malabsorption common (60%)
  • Gastrinomas may rarely arise in mesentery, peritoneum, spleen, skin, mediastinum (usually metastatic)
  • Genetics: 25-30% linked to autosomal dominant MEN1 syndrome (tumors in pancreas, pituitary, parathyroid)
  • Sporadic cases also occur

RISK FACTORS

  • MEN1 syndrome
  • Family history of ulcer disease

COMMONLY ASSOCIATED CONDITIONS

  • MEN1
  • Insulinoma
  • Carcinoid tumors

DIAGNOSIS

History

  • Average symptom duration 5 years before diagnosis
  • Symptoms:
  • Abdominal pain (80%)
  • Diarrhea (70%) (postprandial and fasting)
  • Heartburn (60%)
  • Nausea (30%)
  • Vomiting resistant to standard therapy
  • Weight loss
  • Signs of MEN1: hypercalcemia, hyperparathyroidism, Cushing syndrome

Physical Exam

  • Hepatomegaly (metastasis)
  • Conjunctival pallor (anemia)
  • Jaundice (bile duct compression)
  • Epigastric tenderness
  • Dental erosions
  • Positive fecal occult blood test
  • Complications: ulcer hemorrhage, perforation, obstruction

Differential Diagnosis

  • Hypergastrinemia with hypochlorhydria/achlorhydria: atrophic gastritis, PPI use, gastric cancer, pernicious anemia
  • Hypergastrinemia with normal/increased acid: antral G-cell hyperfunction, chronic renal failure, H. pylori infection, gastric outlet obstruction, retained gastric antrum

DIAGNOSTIC TESTS & INTERPRETATION

  • Serum gastrin:

  • 1,000 pg/mL with gastric pH <2 is diagnostic

  • 200 pg/mL with ulcers is suggestive

  • Secretin stimulation test: Preferred if gastrin borderline or suspicion high
  • Gastric pH: Confirm acid hypersecretion (<2)
  • Gastric acid output: Basal acid output >15 mEq/hr
  • Imaging:
  • Endoscopic ultrasound (EUS) to localize tumor (duodenal/pancreatic)
  • Abdominal CT for pancreatic tumors and metastases (>3 cm)
  • Somatostatin receptor scintigraphy (SRS), 68Ga-DOTATATE PET/CT for small tumors/metastases
  • Selective venous sampling for gastrin may assist localization
  • MEN1 workup: Serum calcium, phosphorus, cortisol, prolactin, brain MRI if indicated

TREATMENT

General Measures

  • Control acid hypersecretion medically
  • Surgical resection if tumor localized and resectable
  • Surgery may reduce need for lifelong antisecretory therapy

Medications

  • First Line: Proton pump inhibitors (PPIs) (often high dose)
  • Omeprazole 60-120 mg/day
  • Lansoprazole 60-180 mg/day (split doses >120 mg)
  • Rabeprazole 60-100 mg/day
  • Pantoprazole 40-240 mg/day
  • H2 blockers: Used if PPI not tolerated; doses higher than usual
  • Adjust doses in elderly or renal insufficiency

  • Correct hypercalcemia if MEN1 present

  • Second Line:

  • Octreotide (somatostatin analog) may slow liver metastases growth
  • Chemotherapy (streptozocin, 5-FU)
  • Interferon (limited efficacy)

Surgery

  • Laparotomy for resection if no metastasis or MEN1
  • Resection improves prognosis; 5-year cure rate ~40% when all tumors removed
  • Reoperation for recurrent tumors may prolong life
  • Total gastrectomy rarely indicated
  • MEN1 gastrinomas often small, multiple; surgery less curative

ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS

  • Titrate medical therapy for symptom control
  • Monitor for metastatic progression

ONGOING CARE

  • Longitudinal follow-up with imaging for metastasis and tumor growth
  • Advise patients on lifelong need for antisecretory therapy
  • Gastric acid analysis to guide therapy, aiming basal acid output <10 mEq/hr (<2 mEq/hr if complications)

DIET

  • Restrict foods that exacerbate symptoms

PATIENT EDUCATION

  • Inform about chronic nature and prognosis
  • Warn against abrupt discontinuation of antisecretory meds

PROGNOSIS

  • Overall 5-10 year survival 69-94%
  • With liver metastasis at diagnosis: 5-year survival 30-40%; 10-year survival 25%
  • Prognosis worsens with metastasis, tumor size, pancreatic location

COMPLICATIONS

  • Peptic ulcer disease complications: bleeding, perforation, obstruction
  • 2/3 of gastrinomas malignant with metastases
  • Paraneoplastic syndromes: ACTH production causing Cushing syndrome
  • Possible vitamin B12 deficiency with long-term PPI use

ICD10

  • E16.4 Increased secretion of gastrin

Clinical Pearls

  • Consider ZES with recurrent or refractory ulcers or need for high-dose PPIs
  • Abdominal pain and diarrhea should be controllable with adequate medical therapy
  • ~25-30% of ZES cases are MEN1-associated
  • Gastrinomas mainly found in pancreatic head and duodenal wall
  • Lifelong PPI therapy is generally required for ulcer healing and symptom control