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Chromogranin A 

  • Author: Georges Elhomsy, MD; Chief Editor: Eric B Staros, MD  more...
 
Updated: Nov 21, 2014
 

Reference Range

Chromogranin A is a secretory protein, composed of 439 amino acids, found in the large dense-core vesicles of the neuroendocrine cells. It belongs to the family of granins that includes chromogranin B, chromogranin C, and secretogranin II.

Chromogranin A can be either measured in the serum or detected by immunohistochemistry in a tissue specimen.

Although it varies widely with the techniques used, the reference ranges for serum chromogranin A are as follows:

  • Less than 36.4 ng/mL (conventional unit) [1]
  • Less than 36.4 µg/L (system international)
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Interpretation

A wide variety of neuroendocrine tumors stain positive for chromogranin A.

Gastro-entero-pancreatic neuroendocrine tumors that stain positive for chromogranin A are as follows[2, 3] :

  • Carcinoid tumor
  • Gastrinoma
  • Insulinoma
  • Glucagonoma
  • VIPoma
  • Somatostatinoma

Thyroid/parathyroid tumors that stain positive for chromogranin A are as follows:

  • Medullary thyroid cancer
  • Parathyroid tumors

Nervous system tumors that stain positive for chromogranin A are as follows:

  • Ganglioneuroma
  • Ganglioneuroblastoma
  • Neuroblastoma
  • Medulloblastoma

Adrenal system tumors that stain positive for chromogranin A include pheochromocytoma. Lung tumors include small cell cancer.

Elevation in serum CgA correlates with the size, extension and the histopathology of the neuroendocrine tumors; it is usually higher in large, metastatic, and well-differentiated tumors. Elevation is mainly detected in the following:

CgA can also be elevated in prostate adenocarcinoma. Serum chromogranin A can be elevated in other situations and conditions, including chronic proton-pump inhibitors use, renal failure, liver failure, heart failure, rheumatoid arthritis, inflammatory bowel disease, and hypertension.

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Collection and Panels

See the list below:

  • Patient instruction: No need for fasting
  • Collection tube: Red top tube or gel-barrier tube
  • Unacceptable Conditions: Grossly hemolyzed specimens
  • Specimen Preparation: Separate serum from cells and transfer to transport tube.
  • Storage/Transport Temperature: Refrigerated or frozen
  • Stability : 2 weeks (refrigerated); 6 weeks (frozen)
  • Panels: None
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Background

Description

Chromogranin A (CgA) is a secretory protein, composed of 439 amino acids, found in the large dense-core vesicles of the neuroendocrine cells. It belongs to the family of granins that includes chromogranin B, chromogranin C, and secretogranin II. Chromogranin A contains multiple cleavage sites, which undergo a tissue-specific proteolytic process, leading to the production of many biologically active peptides including vasostatin I, vasostatin II, pancreastatin, catestatin, parastatin, and serpinin.[4, 5, 6, 7]

CgA is co-stored with a tissue-specific peptide hormone or neuropeptide and exerts an autocrine and paracrine effect on secretory activity of the neuroendocrine cells. Cumulative evidences suggest that CgA’s derived peptides are involved in a wide range of activities, like regulation of blood pressure (catestatin), glucose metabolism (pancreastatin, catestatin), neuroprotection (serpinin), and tumor angiogenesis (vasostatin I, vasostatin II).

Indications/Applications

Chromogranin A can be used, in conjunction with other testing modalities, as a diagnostic tool, but caution is advised since it is elevated in many other conditions. However, chromogranin A might have some prognostic significance.

Serum CgA can be used to monitor neuroendocrine tumor progression after a surgical intervention as well as medical therapy, with the only exception being somatostatin analogs that inhibit tumor secretion rather than causing tumor reduction. Serum CgA should be measured at the same laboratory using the same technique, since the test is still not standardized.[8]

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Contributor Information and Disclosures
Author

Georges Elhomsy, MD Fellow in Endocrinology, St Louis University School of Medicine

Georges Elhomsy, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American Thyroid Association, Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Eric B Staros, MD Associate Professor of Pathology, St Louis University School of Medicine; Director of Clinical Laboratories, Director of Cytopathology, Department of Pathology, St Louis University Hospital

Eric B Staros, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology

Disclosure: Nothing to disclose.

References
  1. Appendix: Normal Hormone Reference Ranges. Greenspan's Basic & Clinical Endocrinology,. Ninth Edition. The McGraw-Hill Companies; 2011.

  2. Qiao XW, Qiu L, Chen YJ, Meng CT, Sun Z, Bai CM, et al. Chromogranin A is a reliable serum diagnostic biomarker for pancreatic neuroendocrine tumors but not for insulinomas. BMC Endocr Disord. 2014 Aug 7. 14:64. [Medline]. [Full Text].

  3. van Adrichem RC, Hofland LJ, Feelders RA, De Martino MC, van Koetsveld PM, van Eijck CH, et al. Chromogranin A, Ki-67 index and IGF-related genes in patients with neuroendocrine tumors. Endocr Connect. 2013. 2(4):172-7. [Medline]. [Full Text].

  4. Glinicki P, Jeske W. Chromogranin A (CgA)--the influence of various factors in vivo and in vitro, and existing disorders on its concentration in blood. Endokrynol Pol. 2010 Jul-Aug. 61(4):384-7.

  5. Loh YP, Cheng Y, Mahata SK, Corti A, Tota B. Chromogranin A and Derived Peptides in Health and Disease. J Mol Neurosci. 2012 Mar 3.

  6. Nobels FR, Kwekkeboom DJ, Bouillon R, Lamberts SW. Chromogranin A: its clinical value as marker of neuroendocrine tumours. Eur J Clin Invest. 1998 Jun. 28(6):431-40.

  7. Arnold R, Wilke A, Rinke A, Mayer C, Kann PH, Klose KJ, et al. Plasma chromogranin A as marker for survival in patients with metastatic endocrine gastroenteropancreatic tumors. Clin Gastroenterol Hepatol. 2008 Jul. 6(7):820-7.

  8. Korse CM, Taal BG, de Groot CA, Bakker RH, Bonfrer JM. Chromogranin-A and N-terminal pro-brain natriuretic peptide: an excellent pair of biomarkers for diagnostics in patients with neuroendocrine tumor. J Clin Oncol. Epub 2009 Aug 10; 2009 Sep 10. 27(26):4293-9.

 
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