Sources of Elevated Chromogranin A (CgA)
Chromogranin A can be elevated in numerous conditions beyond neuroendocrine tumors, including medication use, organ dysfunction, and various pathological states, which must be considered when interpreting elevated levels. 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
- Highest levels are typically observed in patients with carcinoid tumors, with particularly high frequency of elevation in gastrinomas (100%), pheochromocytomas (89%), carcinoid tumors (80%), and nonfunctioning pancreatic endocrine tumors (69%) 3
- Medullary thyroid carcinomas show elevated CgA in approximately 50% of cases 3
- Elevated CgA levels strongly correlate with tumor volume, meaning small neuroendocrine tumors may go undetected with this marker alone 1, 3
Non-Neuroendocrine Tumors
- Hepatocellular carcinoma may show elevated CgA levels in over one-third of patients, possibly indicating neuroendocrine differentiation in some cases 4
- Prostate cancer can demonstrate elevated CgA levels, which may be independent of prostate-specific antigen (PSA) elevation 5
- Some adenocarcinomas may show elevated CgA levels due to neuroendocrine differentiation, which can be confirmed with specialized immunohistochemical techniques 6
Medication-Induced Elevations
- Proton pump inhibitors (PPIs) cause significant false elevations in CgA levels and should be discontinued at least 1 week before measurement 7, 1, 8
- Antacids can also affect CgA levels and should be considered when interpreting results 7
Organ Dysfunction
- Renal failure can cause markedly elevated CgA levels that may reach concentrations otherwise seen only in neuroendocrine neoplasia 9, 1
- Hepatic failure can result in increased CgA levels, though typically not as dramatic as renal failure 9
Other Conditions
- Chronic gastritis, particularly atrophic gastritis, can lead to elevated CgA levels 1, 6
- Hypertension has been associated with spuriously elevated CgA levels 1
- Venipuncture alone can result in modest increases (approximately 12%) in plasma CgA levels 9
Clinical Considerations
- When evaluating elevated CgA, it's essential to rule out medication effects (especially PPIs) and organ dysfunction before attributing the elevation to neuroendocrine pathology 1, 8
- CgA levels exceeding twice the normal limit are associated with shorter survival times in patients with metastatic NETs (HR, 2.8; 95% CI, 1.9–4.0; P<.001) 1
- Rising CgA levels in an asymptomatic patient with stable imaging does not necessarily indicate the need for new therapy 1, 8
Complementary Markers
- When CgA results are equivocal, consider testing for chromogranin B, which may be elevated when CgA is in the reference range 1, 8
- Pancreastatin is specifically elevated in metastatic neuroendocrine tumors and not affected by conditions that commonly elevate CgA 1, 8
- 5-Hydroxyindoleacetic acid (5-HIAA) is particularly useful for serotonin-producing tumors 1, 8