Should you order both a serum gastrin and a chromogranin A (CgA) test on a patient with chronic diarrhea, acid reflux, and unexplained fatigue and weight loss?

Should You Order Both Serum Gastrin and Chromogranin A?

Yes, order both serum gastrin and chromogranin A in this patient with chronic diarrhea, acid reflux, and unexplained weight loss, as these symptoms raise clinical suspicion for gastrinoma—a rare but treatable neuroendocrine tumor that requires both tests for proper evaluation. 1

Clinical Rationale for Testing

Your patient's symptom constellation—chronic diarrhea with acid reflux and weight loss—is classic for gastrinoma (Zollinger-Ellison syndrome). 1, 2 The National Comprehensive Cancer Network specifically recommends suspecting gastrinoma when severe gastroduodenal ulcer symptoms are accompanied by diarrhea. 1 Chronic diarrhea often precedes ulcer symptoms in gastrinoma patients. 1

Why Both Tests Are Necessary

Serum Gastrin: The Primary Diagnostic Test

• Measure fasting serum gastrin after discontinuing PPIs for at least 1 week—this is the most critical step and the most common source of diagnostic error. 1, 3
• Fasting gastrin >10 times the upper limit of normal (>1000 pg/ml) plus gastric pH <2 is diagnostic of gastrinoma. 1
• However, comparable gastrin elevations can occur in pernicious anemia, atrophic gastritis, renal insufficiency, and with PPI therapy. 4
• In borderline cases, a secretin stimulation test should be performed. 1, 4

Chromogranin A: The Complementary Marker

• Chromogranin A is the best general serum marker for neuroendocrine tumors, elevated in 60% or more of patients with both functioning and non-functioning NETs. 3, 5
• It helps distinguish true gastrinoma from non-tumoral hypergastrinemia (autoimmune gastritis, PPI use). 6, 7
• Chromogranin A levels ≥2 times the upper limit of normal correlate with tumor volume and predict shorter survival (HR 2.8; 95% CI 1.9-4.0; P<0.001). 3, 5
• Critical caveat: Chromogranin A is falsely elevated by PPIs, renal failure, liver failure, hypertension, and chronic gastritis—you must exclude these before interpretation. 3, 5

The Diagnostic Algorithm

1. Before ordering any tests: Document whether the patient is taking PPIs (discontinue for ≥1 week), assess renal and liver function, and check blood pressure. 3, 1

2. Order both tests simultaneously: Fasting serum gastrin AND chromogranin A. 1, 3

3. Interpret results in context:

   • High gastrin + high chromogranin A = likely gastrinoma, proceed to imaging. 1, 3
   • High gastrin + normal chromogranin A = consider autoimmune gastritis, check gastric pH and perform upper endoscopy with biopsy. 1, 6
   • Normal gastrin + high chromogranin A = consider other neuroendocrine tumors (carcinoid, VIPoma). 3, 5

4. If gastrinoma is suspected: Obtain multiphasic CT or MRI of abdomen/pelvis, followed by somatostatin receptor scintigraphy (Octreoscan). 3, 5, 1

Important Pitfalls to Avoid

• Do not interpret gastrin levels while the patient is on PPIs—this is the single most common diagnostic error and will cause false elevation. 1, 3
• Do not assume all elevated gastrin is gastrinoma—achlorhydria and atrophic gastritis are far more common causes. 1, 6
• Do not rely on chromogranin A alone—it lacks specificity for gastrinoma and can be normal even with carcinoids. 8, 3
• Chromogranin A is elevated in only 60% of NETs, so a normal level does not exclude the diagnosis. 3

When Hormone Testing Is Recommended

The British Society of Gastroenterology guidelines state that testing for excess vasoactive intestinal peptide, gastrin, or glucagon is recommended only in the presence of high-volume watery diarrhea when other causes have been excluded. 4 However, your patient's combination of chronic diarrhea with acid reflux and weight loss creates sufficient clinical suspicion to warrant testing before exhausting all other possibilities, as gastrinomas are treatable and delays in diagnosis worsen outcomes. 1, 2

Additional Considerations

• Evaluate for Multiple Endocrine Neoplasia Type 1 (MEN1) syndrome in all patients with suspected gastrinoma, as gastrinoma is one of the most common pancreatic NETs in MEN1. 1
• Most gastrinomas (approximately 70%) are located in the duodenum, not the pancreas, and 80-90% have metastatic potential. 1
• Upper endoscopy with gastric biopsy is always required to differentiate gastrinoma from autoimmune atrophic gastritis. 1