Causes of Elevated Chromogranin A (CgA) Levels
Elevated chromogranin A levels can be caused by neuroendocrine tumors, proton pump inhibitor use, renal or hepatic insufficiency, hypertension, and chronic gastritis, with proton pump inhibitors being the most common cause of false elevations. 1, 2
Neuroendocrine Tumors
- CgA is elevated in 60% or more of patients with both functioning and non-functioning pancreatic neuroendocrine tumors, making it the best general neuroendocrine serum marker available 1
- Elevated CgA levels strongly correlate with tumor volume in neuroendocrine tumors, with levels twice the normal limit associated with shorter survival times 1
- CgA is particularly useful for monitoring appendiceal carcinoid tumors, with elevated levels associated with recurrence and poorer survival outcomes 3
Medication-Related Causes
- Proton pump inhibitors (PPIs) are the most common cause of falsely elevated CgA levels, with significant increases occurring within days of starting therapy, even at low doses 2, 4
- Healthcare providers should temporarily stop omeprazole treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high 2
- H₂-receptor blockers can also cause substantial increases in blood CgA concentration 5
Gastrointestinal Conditions
- Chronic atrophic gastritis (type A) can cause substantial increases in CgA levels 5, 6
- Inflammatory bowel disease (ulcerative colitis and Crohn's disease) may have a moderate influence on CgA concentration 5
- Gastrin causes enterochromaffin-like cell hyperplasia which increases serum CgA levels 2
Renal and Hepatic Disorders
- Impaired renal function can cause substantial increases in CgA levels 1, 5
- Deteriorating liver function may have a moderate influence on CgA concentration 5
- Hepatocellular carcinoma has been associated with elevated CgA levels in over one-third of patients 7
Other Medical Conditions
- Prostate cancer and benign prostatic hyperplasia (BPH) can cause substantial increases in CgA 5
- Rheumatoid arthritis with high levels of RF IgM can elevate CgA 5
- Untreated essential hypertension, heart failure, and hypercortisolism may have moderate influence on CgA levels 5
- Advanced age and creatinine levels are significantly related to higher CgA levels 4
Important Clinical Considerations
- When interpreting CgA results, consider the type of biological material tested (serum vs. plasma) 5
- For patients on PPIs, CgA levels can increase dramatically (tenfold in some cases) and quickly normalize after medication withdrawal 8
- Rising CgA levels in an asymptomatic patient with stable imaging does not necessarily indicate the need for new therapy 1
- When serial CgA tests are performed for monitoring, the same commercial laboratory should be used, as reference ranges between tests may vary 2
Alternative Markers When CgA Is Unreliable
- Chromogranin B may be elevated when Chromogranin A is in the reference range, making it a useful additional marker 1, 3
- Pancreastatin is specifically elevated in metastatic neuroendocrine tumors and not affected by conditions that commonly elevate CgA 1, 3
- 5-Hydroxyindoleacetic acid (5-HIAA), a metabolite of serotonin, may be considered as a complementary biochemical marker, particularly for serotonin-producing tumors 1, 3