Workup of Suspected Gastrinoma
Stop all proton pump inhibitors for 1-2 weeks, then measure fasting serum gastrin levels and gastric pH—this is the single most critical diagnostic step and the most common source of error when omitted. 1, 2
Initial Biochemical Testing
- Measure fasting serum gastrin after discontinuing PPIs for at least 1 week (preferably 1-2 weeks), as PPI use is the most common cause of diagnostic error and false elevation 1, 2
- Fasting gastrin >10 times the upper limit of normal plus gastric pH <2 is diagnostic of gastrinoma 1
- Measure gastric pH simultaneously—this is the key discriminator between gastrinoma (pH <2) and the far more common causes of hypergastrinemia like atrophic gastritis (pH >4-5) 1, 3, 2
- Perform secretin stimulation test in equivocal cases where gastrin levels are elevated but not diagnostic 1, 2
Endoscopic Evaluation
- Perform upper endoscopy (EGD) with gastric biopsy in all patients to differentiate gastrinoma from autoimmune atrophic gastritis, which is a much more common cause of hypergastrinemia 1, 2
- Assess for peptic ulcer disease and esophagitis during endoscopy 2
- Note that gastrinomas are subepithelial neuroendocrine tumors arising from deeper layers, making standard mucosal biopsies non-diagnostic for the tumor itself 2
Screening for MEN1 Syndrome
- Evaluate all patients for Multiple Endocrine Neoplasia Type 1 (MEN1) syndrome, as gastrinoma is one of the most common pancreatic neuroendocrine tumors in MEN1 patients 1, 2
- Check serum calcium and parathyroid hormone levels to screen for hyperparathyroidism associated with MEN1 4
Tumor Localization Studies
Once biochemical diagnosis is confirmed, proceed with imaging to localize the tumor:
- Gallium-68 DOTATATE PET/CT is currently the standard for tumor localization in Zollinger-Ellison syndrome 2
- Obtain multiphase CT or MRI of the abdomen and pelvis to look for duodenal or pancreatic gastrinoma 3, 2
- Perform endoscopic ultrasound (EUS) for tumor localization, particularly for pancreatic gastrinomas (sensitivity up to 83%) and small duodenal lesions 3, 2
- Somatostatin receptor scintigraphy (octreotide scan) is useful for initial evaluation of suspected gastrinomas 2, 4
Anatomic Considerations for Localization
- Approximately 70% of gastrinomas are located in the duodenum, not the pancreas, and are typically small 1, 2
- The remainder are found in the pancreas, usually within the "gastrinoma triangle" (confluence of cystic and common bile ducts, junction of second and third portions of duodenum, and junction of neck and body of pancreas) 2
- Duodenal gastrinomas may be multiple, especially in MEN1 patients 1
Additional Laboratory Studies
- Complete blood count to assess for anemia from chronic GI bleeding 5
- Comprehensive metabolic panel including renal function, as renal failure is a common cause of hypergastrinemia that must be ruled out 2
Key Diagnostic Pitfalls to Avoid
- Do not interpret gastrin levels while the patient is on PPIs or H2 antagonists—this is the most common cause of diagnostic error 1, 2
- Do not assume all elevated gastrin represents gastrinoma, as achlorhydria and atrophic gastritis are far more common causes 1
- Do not rely on a therapeutic trial of pancreatic enzymes for diagnosis, as this is unreliable 2
- Remember that 80-90% of gastrinomas have metastatic potential, so staging is essential 1