What are the next steps for a patient with persistent hypergastrinemia (elevated gastrin level) after surgery to remove a gastric neuroendocrine tumor?

Persistent Hypergastrinemia After Gastric NET Resection

Your patient likely has Type 1 gastric neuroendocrine tumor with underlying chronic atrophic gastritis causing persistent hypergastrinemia—the elevated gastrin is from the gastritis, not residual tumor, and requires endoscopic surveillance rather than additional surgery. 1, 2

Determine the Type of Gastric NET

The key to management is identifying which type of gastric NET your patient had, as this determines whether persistent hypergastrinemia indicates residual disease or an underlying gastric condition:

Type 1 (Most Common - 70-80% of gastric NETs)

• Associated with chronic atrophic gastritis causing achlorhydria and secondary hypergastrinemia 3
• Gastrin remains elevated even after complete tumor resection because the underlying gastritis persists 2, 4
• Multiple small polyps typically in gastric body/fundus 3
• Excellent prognosis with <2% metastatic potential 3

Type 2 (Rare - 5-6% of gastric NETs)

• Associated with gastrinoma (Zollinger-Ellison syndrome) and often MEN-1 1, 3
• Persistent hypergastrinemia after NET resection indicates the gastrinoma is still present 1
• Requires identification and resection of the gastrinoma itself 1

Type 3 (Sporadic - 15-20% of gastric NETs)

• Not associated with hypergastrinemia 3
• Solitary, larger tumors with aggressive behavior 3
• If gastrin is elevated post-resection, this is NOT a Type 3 tumor 3

Immediate Next Steps

1. Confirm You're Not Measuring a False Elevation

• Stop proton pump inhibitors for 1-2 weeks and remeasure fasting gastrin 1, 5, 6
• PPIs are the most common cause of spurious hypergastrinemia and must be discontinued before interpretation 1, 7, 6
• Check renal function, liver function, and blood pressure as these cause false elevations 1, 7

2. Measure Gastric pH

• If fasting gastrin >1000 pg/mL (your patient has 2135 ng/L = ~2135 pg/mL) AND gastric pH <2, this indicates gastrinoma (Type 2) 6, 8
• If gastric pH >4-5, this indicates achlorhydria from atrophic gastritis (Type 1) 8, 2
• This single test distinguishes between the two gastrin-dependent types 6, 8

3. Obtain Upper Endoscopy with Biopsies

• Look for chronic atrophic gastritis, intestinal metaplasia, and parietal cell loss in the gastric body/fundus (Type 1) 2, 9
• Assess for new or recurrent NET polyps 1, 4
• Check for gastric parietal cell antibodies and intrinsic factor antibodies (positive in autoimmune atrophic gastritis) 2

4. Imaging to Exclude Gastrinoma or Metastatic Disease

• Obtain multiphasic CT or MRI of abdomen/pelvis to look for duodenal or pancreatic gastrinoma 1, 6
• Consider somatostatin receptor scintigraphy (Octreoscan) if gastrinoma is suspected 1
• Approximately 70% of gastrinomas in MEN-1 patients are duodenal 1

Management Based on Type

If Type 1 (Atrophic Gastritis-Related)

• Surveillance endoscopy every 6-12 months for the first 3 years, then annually 1
• The hypergastrinemia will persist indefinitely because the atrophic gastritis is permanent 2, 4
• Consider antrectomy ONLY if new lesions or increasing tumor burden develops 1
• Octreotide LAR 20 mg IM every 28 days can cause tumor regression and normalize gastrin temporarily, but tumors typically don't recur even when gastrin rises again after stopping therapy 4
• Monitor for vitamin B12 deficiency (pernicious anemia) 9

If Type 2 (Gastrinoma-Related)

• Locate and resect the gastrinoma (usually duodenal or pancreatic) 1
• Use EUS for small duodenal gastrinomas 1
• Long-term octreotide LAR for symptom control if gastrinoma is unresectable 1
• Screen for MEN-1 syndrome 1

Critical Pitfalls to Avoid

• Do not assume persistent hypergastrinemia means residual NET—it usually indicates the underlying cause (atrophic gastritis or gastrinoma) is still present 2, 4
• Do not interpret gastrin levels while patient is on PPIs—this is the single most common diagnostic error 1, 7, 5, 6
• Do not perform antrectomy for Type 1 gastric NETs unless there is documented progression or new lesions 1
• Chromogranin A is elevated in only 60% of NETs and is falsely elevated by PPIs, renal failure, and hypertension—it should not be used as the primary marker for recurrence 1, 7, 6

Monitoring Strategy

• Endoscopic surveillance every 6-12 months for 3 years, then annually 1
• Imaging only as clinically indicated (not routine) 1
• Gastrin levels will remain elevated in Type 1 and do not require treatment unless new tumors develop 2, 4