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Chromogranin A (CgA)

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A Quick Guide for Patients

  • What is Chromogranin A (CgA)? CgA is a protein released by special cells called neuroendocrine cells. It's used as a blood test to help find and monitor neuroendocrine tumors (NETs).
  • A Sensitive but Not Perfect Test: While CgA is a very sensitive marker for NETs, a high level doesn't automatically mean you have cancer. Many other things can cause it to rise.
  • Medication Matters: Common acid reflux medicines (like Prilosec, Nexium) can significantly raise CgA levels. It's crucial to tell your doctor about all medications you take.
  • The Trend is Key: A single CgA reading is less important than the pattern over time. Doctors look at whether the level is consistently rising, falling, or stable to track the disease and treatment response.

Chromogranin A (CgA) Overview

Chromogranin A (CgA) is a 49-kDa acidic glycoprotein stored and released with catecholamines and other peptide hormones from secretory granules of neuroendocrine cells. It is widely expressed in neurons, endocrine tissues, and neuroendocrine tumor (NET) cells. Elevated serum CgA is a sensitive but non-specific marker for neuroendocrine tumors.

CgA measurement is primarily used in the diagnosis, monitoring of treatment response, and surveillance for recurrence in patients with neuroendocrine tumors (NETs), particularly gastroenteropancreatic NETs (GEP-NETs) and pheochromocytomas.

Tumour markers serve as indispensable tools in the realm of cancer detection and diagnosis, offering valuable insights into disease progression and treatment response.

Indications for CgA Testing

CgA testing is indicated in:

  1. Diagnosis of NETs: Especially in patients with suspected carcinoid syndrome, pancreatic NETs, or pheochromocytoma/paraganglioma.
  2. Treatment Monitoring: Assessing response to surgery, somatostatin analogs (SSAs), peptide receptor radionuclide therapy (PRRT), or chemotherapy.
  3. Surveillance: Detecting recurrence after curative resection, particularly in well-differentiated NETs.
  4. Prognostic Stratification: Elevated baseline CgA correlates with tumor burden and poorer prognosis.

CgA Biology and Function

CgA is a member of the granin family, processed into biologically active peptides such as vasostatin, pancreastatin, and catestatin. It regulates granule biogenesis and hormone secretion. CgA is co-secreted with amines and peptides from neuroendocrine cells in response to stimuli.

Its widespread expression in neuroendocrine tissues makes it a pan-neuroendocrine marker. Circulating CgA is stable and measurable by immunoassays (ELISA, RIA).

CgA in Neuroendocrine Tumors (NETs)

Elevated CgA is found in >60–90% of NETs depending on grade and site:

  • Carcinoid Tumors: Especially midgut NETs with liver metastases; correlates with tumor burden and carcinoid heart disease risk.
  • Pancreatic NETs: High sensitivity in insulinomas, gastrinomas, and non-functioning pNETs.
  • Pheochromocytoma/Paraganglioma: Often markedly elevated; useful when plasma metanephrines are inconclusive.
  • Medullary Thyroid Carcinoma (MTC): Elevated in ~50–70% of cases.

A >25–50% reduction in CgA post-treatment indicates biochemical response; rising levels suggest progression.

Frequently Asked Questions (FAQ)

My CgA level is high. Do I definitely have a neuroendocrine tumor?

Not at all. While CgA is the best general marker for NETs, it is not specific. The most common non-cancerous cause of a high CgA level is the use of proton pump inhibitors (PPIs)—medications for acid reflux. Other conditions like kidney disease, heart failure, and even stress can also raise levels. Your doctor will use the CgA result as a clue and will always interpret it with other tests and your overall clinical picture.

Why do I need to stop my acid reflux medication (PPI) before the test?

Proton pump inhibitors (PPIs) like omeprazole (Prilosec) or esomeprazole (Nexium) work by strongly reducing stomach acid. The body responds to this by increasing the production of a hormone called gastrin, which in turn stimulates certain neuroendocrine cells in the stomach to grow and release more CgA. This can lead to a falsely high CgA level, making the test difficult to interpret. Stopping the medication for 1-2 weeks (with your doctor's approval) allows the level to return to its true baseline.

What does it mean if my CgA level changes during treatment?

This is one of the most valuable uses of the CgA test. If you have been diagnosed with a NET, doctors will measure your CgA level before and during treatment. A significant drop in the CgA level is a good sign that the treatment is working. Conversely, a steady rise in CgA after treatment may be the earliest indicator that the tumor is growing or recurring, often prompting further investigation with imaging scans.

Interpreting CgA Levels

Reference range: <15–100 ng/mL (assay-dependent). Interpretation requires:

  • Serial Measurements: Single values are less informative; trends are critical.
  • Tumor Grade: Higher in well-differentiated (G1/G2) than poorly differentiated (G3) NETs.
  • Assay Standardization: Variability between assays; use same lab for follow-up.

Levels >1000 ng/mL often indicate high tumor burden or liver involvement.

Limitations and Confounding Factors

CgA is non-specific and may be elevated in:

  • Proton pump inhibitor (PPI) use (gastric enterochromaffin-like cell hyperplasia)
  • Renal impairment (reduced clearance)
  • Chronic atrophic gastritis
  • Heart failure, hypertension
  • Non-NET malignancies (prostate, breast, ovarian)

Discontinue PPIs 1–2 weeks before testing if possible.

CgA in Other Conditions

Besides NETs, CgA may be mildly elevated in:

  • Hyperparathyroidism
  • Chronic liver disease
  • Inflammatory bowel disease
  • Stress or essential hypertension

Not recommended as a screening tool in asymptomatic individuals due to low specificity.

Expert Interpretation is Key

CgA test results can be complex due to the many factors that can influence them. This information is for educational purposes and is not a substitute for professional medical advice. Always discuss your results with your healthcare provider to understand their meaning in your specific situation.

Consult with a Specialist at MIN Clinic

References

  1. O'Toole D, Grossman A, Gross R, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Biochemical Markers. Neuroendocrinology. 2017;105(3):266-281. https://doi.org/10.1159/000473854
  2. Lab Tests Online. Chromogranin A. Reviewed November 27, 2023. American Association for Clinical Chemistry. Retrieved from https://lto.aacc.org/Tests/Chromogranin-A
  3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Neuroendocrine and Adrenal Tumors. Version 1.2024. Available at https://www.nccn.org/guidelines/category_1. Accessed April 24, 2024.
  4. Vinjamuri S. The Role of Chromogranin A in Neuroendocrine Tumors. In: Paz-Ares LG, editor. Cancer. [Internet]. Brisbane (AU): Codon Publications; 2019 Nov 27. Chapter 12. Available from: https://www.ncbi.nlm.nih.gov/books/NBK553195/.
  5. Rapp M, Cichon S, Klöppel G, et al. Chromogranin A in Neuroendocrine Tumors: A Critical Reappraisal of Its Clinical Value. Journal of Clinical Endocrinology & Metabolism. 2017;102(12):4383-4395. https://doi.org/10.1210/jc.2017-01306
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