What are the initial diagnostic steps and management for a patient suspected of having Zollinger Ellison syndrome, particularly regarding blood tests and medication like proton pump inhibitors (PPIs) such as omeprazole (prilosec)?

Diagnostic Blood Tests for Zollinger-Ellison Syndrome

The initial diagnostic blood test for suspected Zollinger-Ellison syndrome is a fasting serum gastrin level, which must be obtained after discontinuing proton pump inhibitors (PPIs) for 1-2 weeks. 1, 2

Initial Diagnostic Approach

When to Suspect ZES

Suspect Zollinger-Ellison syndrome in patients presenting with:

• Severe or refractory gastroesophageal reflux disease despite standard PPI therapy 1
• Chronic diarrhea (occurs in approximately 50% at diagnosis) 1
• Multiple peptic ulcers or ulcers in unusual locations 2, 3
• Complicated or refractory peptic ulcers 2, 3
• Epigastric pain lasting years despite acid-suppressive therapy (reported in 70% at diagnosis) 1
• Weight loss 1, 3

Critical First Step: Rule Out Common Causes of Hypergastrinemia

Before pursuing ZES diagnosis, exclude renal failure, which is a common cause of spurious hypergastrinemia. 1, 4 Also exclude:

• Liver failure 4
• Hypertension 4
• Chronic atrophic gastritis 4

Blood Test Protocol

Fasting Serum Gastrin Level

Stop all PPIs for at least 1-2 weeks before measuring fasting serum gastrin. 1, 5, 2 This is the most critical step, as PPIs cause false elevation of gastrin levels and are the most common cause of false positives. 4, 5

• Markedly elevated fasting gastrin (typically >1000 pg/mL) with gastric pH <2 strongly suggests ZES 2, 3
• If gastrin is only mildly elevated, proceed to secretin stimulation test 2, 3

Gastric pH Measurement

After obtaining gastrin levels, measure gastric pH to confirm gastric acid hypersecretion. 1, 6

• pH <2 indicates acid hypersecretion consistent with gastrinoma 6
• pH >4-5 indicates achlorhydria from atrophic gastritis (Type 1 gastric NET, not ZES) 6

Secretin Stimulation Test

For patients with mild hypergastrinemia and suspected ZES, perform a secretin stimulation test. 2, 3 However, note that PPIs must be discontinued at least 14 days before this test to avoid false positive hyper-response. 5

Additional Blood Tests

• Serum chromogranin A (CgA): Stop PPIs for at least 14 days before measuring, as PPI-induced decreases in gastric acidity cause secondary CgA elevation and false positive results 5
• Serum calcium and parathyroid hormone: To screen for Multiple Endocrine Neoplasia Type 1 (MEN-1), as all gastrinoma patients should be considered candidates for MEN-1 syndrome 1, 3

Management Considerations with PPIs

PPI Therapy in Confirmed ZES

Once ZES is diagnosed, high-dose PPIs are the initial treatment of choice. 7, 2, 3

• Starting dose of omeprazole should be 60 mg/day 8
• Basal acid output should be maintained at <5 mEq/h for uncomplicated ZES and <1-2 mEq/h for complicated ZES 3
• In patients with ZES taking voriconazole, dose adjustment of omeprazole may be considered for those requiring higher doses 5

Common Pitfall to Avoid

Do not attempt to diagnose ZES while the patient is taking PPIs. The single most common diagnostic error is measuring gastrin or chromogranin A levels without stopping PPIs first, leading to false positive results. 4, 5 This 1-2 week washout period is mandatory for accurate diagnosis. 1, 5

Tumor Localization After Biochemical Diagnosis

Once biochemical diagnosis is confirmed:

• Gallium-68 PET scan is currently the standard for tumor localization 1
• Multiphasic CT or MRI of abdomen/pelvis 1, 4
• Endoscopic ultrasound (EUS) for pancreatic gastrinomas (sensitivity up to 83%) 1
• Esophagogastroduodenoscopy (EGD) to assess for peptic ulcer disease and esophagitis 1