What Gastrin Levels Evaluate
Gastrin levels primarily evaluate for gastrin-secreting tumors (gastrinomas/Zollinger-Ellison syndrome), distinguish types of gastric neuroendocrine tumors, and identify causes of hypergastrinemia including atrophic gastritis, pernicious anemia, and medication effects from proton pump inhibitors. 1, 2
Primary Clinical Indications for Gastrin Testing
Suspected Gastrinoma/Zollinger-Ellison Syndrome
Gastrin levels should be measured when evaluating patients with:
- High-volume watery diarrhea (>1 liter/day) with dehydration and hypokalemia when other causes have been excluded 1
- Severe or recurrent peptic ulcers, particularly those located in unusual anatomical locations (beyond the duodenal bulb, in the descending duodenum or jejunum), multiple ulcers, or ulcers refractory to standard therapy 1, 2, 3
- Chronic diarrhea with gastroesophageal reflux disease refractory to standard therapy and weight loss 2
- Recurrent peptic ulcer disease with gastrointestinal bleeding in the absence of H. pylori infection 1
- Suspected MEN-1 syndrome (all gastrinoma patients should be evaluated for MEN-1) 1, 2
Diagnostic Interpretation
Fasting serum gastrin >1000 pg/mL combined with gastric pH <2 is diagnostic of gastrinoma 1, 3. Normal gastrin levels are approximately 150 pg/mL, with gastrinoma patients averaging around 1000 pg/mL 1. However, critical pitfall: comparable elevations occur in pernicious anemia, atrophic gastritis, and with proton pump inhibitor therapy 1.
Differential Diagnosis of Hypergastrinemia
Medication-Induced Hypergastrinemia
Proton pump inhibitors (PPIs) and H2 antagonists elevate both gastrin and chromogranin A levels 1, 4. PPIs should be withdrawn with great caution and ideally stopped 10-14 days before measuring fasting gastrin 1, 4. H2 antagonists should be interrupted 48 hours before testing 1. This is the most common cause of spurious hypergastrinemia in clinical practice 5.
Gastric Neuroendocrine Tumor Classification
Gastric pH is the key discriminator between NET types 6:
- Type 1 gastric NETs (70-80% of gastric NETs): pH >4-5 indicates achlorhydria from atrophic gastritis with physiologic hypergastrinemia from parietal cell loss 6
- Type 2 gastric NETs: pH <2 indicates gastrinoma/Zollinger-Ellison syndrome 6
- Type 3 gastric NETs: Gastrin is not elevated 1
Other Causes of Elevated Gastrin
Raised gastrin levels also occur in:
- Renal insufficiency (common cause that must be ruled out before pursuing ZES diagnosis) 2
- Diabetes mellitus 1
- Rheumatoid arthritis 1
Confirmatory Testing Algorithm
When gastrin is elevated but <10 times normal with gastric pH <2:
- Document increased basal acid output (BAO): BAO >15 mmol/h is indicative of gastrinoma in the presence of raised serum gastrin 1
- Calculate BAO/MAO ratio: Ratio >0.6 is highly specific for gastrinoma 7
- Secretin stimulation test: May be necessary in equivocal cases 1
Important contraindications: Basal acid output testing is inappropriate in patients with atrophic gastritis, pernicious anemia, or if PPIs have been used in the previous 14 days 1.
Clinical Context and Limitations
Gastrin testing for hormone-secreting tumors is extremely rare and should only be performed in high-volume watery diarrhea when other causes have been excluded 1. The prevalence of gastrinomas is approximately 1 per million cases per year 1.
Serum gastrin levels fluctuate, so the assay should be performed during an episode of diarrhea 1. Fasting specimens are required after an overnight fast to establish baseline values 4.
Increased gastrin causes enterochromaffin-like (ECL) cell hyperplasia and increased serum chromogranin A (CgA) levels, which may cause false positive results in diagnostic investigations for neuroendocrine tumors 5.