Workup for Zollinger-Ellison Syndrome
The diagnostic workup for Zollinger-Ellison syndrome requires measurement of fasting serum gastrin levels (after discontinuing PPIs for 1-2 weeks), gastric acid secretion analysis, and tumor localization imaging with Gallium-68 PET scanning as the current standard. 1
Clinical Suspicion and Presentation
Suspect ZES in patients presenting with:
- Severe peptic ulceration refractory to standard acid-suppressive therapy with symptoms lasting years 1
- Chronic diarrhea (occurs in approximately 50% at diagnosis) 1
- Gastroesophageal reflux disease unresponsive to conventional treatment 1
- Abdominal pain (reported in 70% at diagnosis) and weight loss 1
- Peptic ulcers combined with kidney stones 2
- Family history of ulcers or endocrine diseases 2
- Watery diarrhea or malabsorption with or without ulcers 2
Critical first step: Rule out renal failure, as it is a common cause of hypergastrinemia that must be excluded before pursuing ZES diagnosis. 1
Biochemical Diagnosis
Fasting Serum Gastrin Level
- Discontinue proton pump inhibitors for 1-2 weeks before testing 1
- Diagnosis is certain when plasma gastrin is >1000 pg/mL combined with basal acid output >15 mEq/h in patients with intact stomach (or >5 mEq/h in gastrectomized patients) 3
- Alternatively, diagnosis is confirmed when hypergastrinemia is associated with gastric pH <2 3
Gastric Acid Secretion Analysis
- Measure basal acid output (BAO) - this is essential and patients cannot be managed safely without it 2
- Target BAO should be reduced to <10 mmol/h for uncomplicated ZES 4
- Target BAO should be <5 mmol/h (or <1-2 mEq/h) for complicated ZES or patients with previous gastric resection or severe esophageal disease 2, 4
Secretin Stimulation Test
- Perform if fasting gastrin levels are equivocal 4
- This test helps differentiate ZES from other causes of hypergastrinemia 4
Tumor Localization Imaging
Primary Imaging Modality
- Gallium-68 radiotracer positron emission tomography (PET) is currently the standard for tumor localization 1
- This has replaced older somatostatin receptor scintigraphy as the preferred initial imaging 1
Additional Cross-Sectional Imaging
- Multiphase CT and MRI scans for optimal detection of gastrinomas 1
- Note: The majority of gastrinomas are located in the duodenum, with the remainder typically in the pancreas 1
- Cross-sectional imaging cannot identify exocrine pancreatic insufficiency but plays an important role in diagnosing pancreatic disease 5
Endoscopic Evaluation
- Endoscopic ultrasound (EUS) and esophagogastroduodenoscopy (EGD) as appropriate for duodenal and gastric evaluation 5
- Perform endoscopy to assess for peptic ulcer disease and esophagitis 5
Screening for Associated Conditions
All patients with gastrinoma should be evaluated for Multiple Endocrine Neoplasia type 1 (MEN1) syndrome 1
- Check serum calcium levels to screen for hyperparathyroidism 3
- Obtain family history of endocrine diseases 2
- 20-38% of ZES cases are associated with MEN1 3
Common Pitfalls to Avoid
- Never stop antisecretory medication except under controlled conditions or unless acid outputs have been surgically reduced 2
- Do not perform fasting gastrin testing while patient is on PPIs - this will yield falsely elevated results 1
- Do not rely on therapeutic trial of pancreatic enzymes for diagnosis - this is unreliable 5
- Recognize that 60% of gastrinoma patients develop metastases, with likelihood correlated to primary tumor size 1
Immediate Management During Workup
Start large doses of antisecretory medication immediately in any patient with suspected ZES - this should never be delayed while awaiting diagnostic confirmation 2