Reporting Name
Chromogranin A, S
Useful For
Follow-up or surveillance of patients with known or treated carcinoid tumors
An adjunct in the diagnosis of carcinoid tumors
An adjunct in the diagnosis of other neuroendocrine tumors, including pheochromocytomas, medullary thyroid carcinomas, functioning and nonfunctioning islet cell and gastrointestinal amine precursor uptake and decarboxylation tumors, and pituitary adenomas
A possible adjunct in outcome prediction and follow-up in advanced prostate cancer
Clinical Information
Chromogranin A (CGA) is a 439-amino acid protein with a molecular weight of 48 to 60 kDa, depending on glycosylation and phosphorylation status. It is a member of the granin family of proteins and polypeptides. Granins are widespread in endocrine, neuroendocrine, peripheral, and central nervous tissues, where they are found in secretory granules alongside the tissue-specific secretion products. The role of granins within the granules is to maintain the regulated secretion of these signaling molecules. This includes:
-Facilitating the formation of secretory granules
-Calcium- and pH-mediated sequestration and resolubilization of hormones or neurotransmitters
-Regulation of neuropeptide and peptide hormone processing through modulation of prohormone convertase activity
In addition, granins contain multiple protease and peptidase cleavage sites and, upon intra- or extracellular cleavage, give rise to a series of daughter peptides with distinct extracellular functions. Some of these have defined functions, such as pancreastatin, vasostatin, and catestatin, while others are less well characterized.(1)
Because of its ubiquitous distribution within neuroendocrine tissues, CGA can be a useful diagnostic marker for neuroendocrine neoplasms, including carcinoids, pheochromocytomas, neuroblastomas, medullary thyroid carcinomas, some pituitary tumors, functioning and nonfunctioning islet cell tumors, and other amine precursor uptake and decarboxylation tumors. It can also serve as a sensitive means for detecting residual or recurrent disease in treated patients.(2-4)
Carcinoid tumors in particular almost always secrete CGA along with a variety of specific modified amines, chiefly serotonin (5-hydroxytryptamine) and peptides.(1-4) Carcinoid tumors are subdivided into foregut carcinoids, arising from respiratory tract, stomach, pancreas or duodenum (approximately 15% of cases); midgut carcinoids, occurring within jejunum, ileum, or appendix (approximately 70% of cases); and hindgut carcinoids, which are found in the colon or rectum (approximately 15% of cases). Carcinoids display a spectrum of aggressiveness with no clear distinguishing line between benign and malignant. In advanced tumors, morbidity and mortality relate as much, or more, to the biogenic amines and peptide hormones secreted, as to local and distant spread. The symptoms of this carcinoid syndrome consist of flushing, diarrhea, right-sided valvular heart lesions, and bronchoconstriction. Serum CGA and urine 5-hydroxyindolacetic acid (5-HIAA) are considered the most useful biochemical markers and are first-line tests in disease surveillance of most patients with carcinoid tumors.(2-4) Serum CGA measurements are used in conjunction with, or alternative to, measurements of serum or whole blood serotonin, urine serotonin and 5-HIAA, and imaging studies. This includes the differential diagnosis of isolated symptoms suggestive of carcinoid syndrome, in particular flushing.
Finally, a number of tumors that are not derived from classical endocrine or neuroendocrine tissues, but contain cells with partial neuroendocrine differentiation, such as small-cell carcinoma of the lung or prostate carcinoma, may also display elevated CGA levels. The role of CGA measurement is not well defined in these tumors, with the possible exception of prognostic information in advanced prostate cancer.(5)
Interpretation
Follow-up/Surveillance:
Urine 5-hydroxyindolacetic acid (5-HIAA) and serum chromogranin A (CGA) increase in proportion to carcinoid tumor burden. Because of the linear relationship of CGA to tumor burden, its measurement also provides prognostic information.
Most mid- and hindgut tumors secrete CGA even if they do not produce significant amounts of serotonin or serotonin metabolites (5-HIAA). Guidelines recommend 3 to 12 monthly measurements of CGA or 5-HIAA in follow-up of midgut carcinoids.(2,3) Patients with foregut tumors can also be monitored with CGA or 5-HIAA measurements if they were positive for these markers at initial diagnosis. Hindgut tumors usually do not secrete serotonin and consequently, only CGA monitoring is recommended.(1-4)
As is typical for tumor marker use in follow-up and surveillance, a 40% to 50% change in serum CGA concentrations should be considered potentially clinically significant in the absence of confounding factors (see Cautions). Much smaller changes in CGA concentrations might be considered significant if they occur over several serial measurements and are all in the same direction.
Adjunct in Diagnosis of Carcinoid Tumors:
CGA is elevated in most patients (approximately 90%) with symptomatic or advanced carcinoids (carcinoid syndrome), usually to levels several times the upper limit of the reference interval. Serum CGA measurements are particularly suited for diagnosing hindgut tumors, being elevated in nearly all cases, even though serotonin and 5-HIAA are often normal. CGA is also elevated in 80% to 90% of patients with symptomatic foregut and midgut tumors.
To achieve maximum sensitivity in the initial diagnosis of suspected carcinoid tumors, serum CGA, serotonin in serum or blood, and 5-HIAA in urine should all be measured. In most cases, if none of these 3 analytes are elevated, carcinoids can usually be excluded as a cause of symptoms suggestive of carcinoid syndrome. For some cases, additional tests such as urine serotonin measurement will be required. An example would be a foregut tumor that does not secrete CGA and only produces 5-hydroxytryptophan (5-HTP) rather than serotonin. In this case, circulating chromogranin, serotonin, and urine 5-HIAA levels would not be elevated. However, the kidneys can convert 5-HTP to serotonin, leading to high urine serotonin levels.
Adjunct in the Diagnosis of Other Neuroendocrine Tumors:
In patients with suspected neuroendocrine tumors other than carcinoids, CGA is often elevated alongside any specific amine and peptide hormones or neurotransmitters that may be produced. The CGA elevations are less pronounced than in carcinoid tumors, and measurement of specific tumor secretion products is considered of greater utility. However, CGA measurements can occasionally aid in diagnosis of these tumors if specific hormone measurements are inconclusive. This is the case in particular with pheochromocytoma and neuroblastoma, where CGA levels may be substantially elevated and can, therefore, provide supplementary and confirmatory information to measurements of specific hormones. In particular, CGA measurements might provide useful diagnostic information in patients with mild elevations in catecholamines and metanephrines;(6) such mild elevations often represent false-positive test results.
Possible Adjunct in Outcome Prediction and Follow-up of Prostate Cancer:
Prostate cancers often contain cells with partial neuroendocrine differentiation. These cells secrete CGA. The amounts secreted are insufficient in most cases to make this a useful marker for prostate cancer diagnosis. However, if patients with advanced prostate cancer are found to have elevated CGA levels, this indicates the tumor contains a significant neuroendocrine cell subpopulation. Such tumors are often resistant to antiandrogen therapy and have a worse prognosis. These patients should be monitored particularly closely.(5)
Report Available
1 to 3 days
Day(s) Performed
Monday through Saturday
Clinical Reference
1. Bartolomucci A, Possenti R, Mahata SK, Fischer-Colbrie R, Loh YP, Salton SRJ: The extended granin family: structure, function, and biomedical implications. Endocr Rev. 2011 Dec;32(6):755-797
2. Boudreaux JP, Klimstra DS, Hassan MM, et al: The NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors: well-differentiated neuroendocrine tumors of the jejunum, ileum, appendix, and cecum. Pancreas. 2010 Aug;39(6):753-766
3. Anthony LB, Stosberg JR, Klimstra DS, et al: The NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors (nets): well-differentiated nets of the distal colon and rectum. Pancreas. 2010 Aug;39(6):767-774
4. Kullke MH, Benson AB, Bergsland E, et al: National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines): NCCN Guidelines Version 1. Neuroendocrine Tumors. 2012:1-94.
5. Tricoli JV, Schoenfeldt M, Conley BA: Detection of prostate cancer and predicting progression: current and future diagnostic markers. Clin Cancer Res. 2004 Jun 15;10(12 Pt 1):3943-3953
6. Algeciras-Schimnich A, Preissner CM, Young WF Jr, Singh RJ, Grebe SKG: Plasma chromogranin A or urine fractionated metanephrines follow-up testing improves the diagnostic accuracy of plasma fractionated metanephrines for pheochromocytomas. J Clin Endocrinol Metab. 2008 Jan;93(1):91-95
7. Korse CM, Muller M, Taal BG: Discontinuation of proton pump inhibitors during assessment of chromogranin A levels in patients with neuroendocrine tumors. Br J Cancer. 2011 Oct 11;105(8):1173-1175
8. Bech PR, Ramachandran R, Dhillo WS, Martin NM, Bloom SR: Quantifying the effects of renal impairment on plasma concentrations of the neuroendocrine neoplasia biomarkers chromogranin A, chromogranin B, and cocaine- and amphetamine-regulated transcript. Clin Chem. 2012 May;58(5):941-943
Method Name
Immunofluorescent Assay (IFA)
Specimen Type
Serum
Specimen Required
Patient Preparation: Proton pump inhibitor medications should be discontinued for at least 2 weeks before collection.
Supplies: Sarstedt Aliquot Tube, 5 mL (T914)
Collection Container/Tube:
Preferred: Serum gel
Acceptable: Red top
Submission Container/Tube: Plastic vial
Specimen Volume: 0.5 mL
Collection Information: Centrifuge and aliquot serum into plastic vial. Do not submit in original tube.
Specimen Minimum Volume
0.2 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Serum | Frozen (preferred) | 90 days | |
| Ambient | 7 days | ||
| Refrigerated | 24 hours |
Reference Values
<93 ng/mL
Reference values apply to all ages.
Test Classification
This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.
CPT Code Information
86316
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| CGAK | Chromogranin A, S | 9811-1 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| CGAK | Chromogranin A, S | 9811-1 |
Forms
If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:
-General Request (T239)
-Oncology Test Request (T729)
FAQs
What does it mean if your chromogranin A is high? ›
An increased Chromogranin A level in a person with symptoms may indicate the presence of a tumor, but it is not specific for the type of tumor or its location. In order to diagnose the condition, the tumor itself must be located, biopsied, and examined by a pathologist.
What level of chromogranin A indicates a tumor? ›A 40% or greater increase of CgA level during follow-up might be a predictive factor for tumor progression or recurrence of GEP-NETs. CgA level has been shown to be elevated in various diseases, including benign and malignant diseases.
What is a chromogranin A serum blood test for? ›Chromogranin A is a reliable serum diagnostic biomarker for pancreatic neuroendocrine tumors but not for insulinomas.
What is the normal range for serum chromogranin A? ›The reference ranges for serum chromogranin A are the following: less than 36.4 ng/ml and less than 36.4 µg/l for conventional unit and system international, respectively.
What medications cause high chromogranin A? ›Medications: omeprazole, losartan, pravastatin, torasemid, acetylsalicylic acid, paracetamol, diclofenac occasionally and ibandronic acid.
What causes raised chromogranin levels? ›Chromogranin A may also be elevated in other tumors that contain neuroendocrine cells such as small-cell carcinoma of the lung and prostate carcinoma. Prostate cancers that secrete chromogranin A are often resistant to anti-androgen therapy.
What is the blood marker for carcinoid tumor? ›Two markers are primarily used to diagnose and follow carcinoid tumours: 5-hydroxy-indole-acetic acid (5-hiaa) and chromogranin A (CgA).
Can stress elevate chromogranin A? ›Results. Although personal stress level were different in each individual, 61% of subjects increase salivary chromogranin A and increase blood pressure and heart rate after mental arithmetic stress.
What is suggestive of neuroendocrine tumor? ›In general, neuroendocrine tumor signs and symptoms might include: Pain from a growing tumor. A growing lump you can feel under the skin. Feeling unusually tired.
What are the symptoms of chromogranin? ›Results: Dyspepsia (66.5%) and weight loss (47.6%) were the most common symptoms at diagnosis, while in 21.4% of patients tumour lesions were revealed incidentally.
What is the clinical significance of chromogranin A? ›
Background: Chromogranin A (CgA) has been shown to be a useful marker in the diagnosis of neuroendocrine (NE) tumours.
What affects chromogranin? ›Among the factors causing a substantial increase of the blood CgA concentration are: treatment with proton-pump inhibitors or H₂-receptor blockers, chronic atrophic gastritis (type A), impaired renal function, prostate cancer and BPH, and rheumatoid arthritis with high level of RF IgM.
What is the best scan for carcinoid tumors? ›Computed tomography (CT) scan
A CT scan is most often used to look at the chest and/or belly (abdomen) to see if GI neuroendocrine (carcinoid) tumors have spread to nearby lymph nodes or other organs such as the liver.
Imaging tests may be used to locate the primary carcinoid tumor and determine whether it has spread. Your doctor may start with a CT scan of your abdomen, because most carcinoid tumors are found in the gastrointestinal tract. Other scans, such as MRI or nuclear medicine scans, may be helpful in certain situations.
What is the most common site of carcinoid tumor? ›In children and young adults, carcinoid tumors are most often found in the appendix, called appendiceal carcinoid tumors, or in the lungs, called bronchial tumors. In adults, carcinoid tumors are most often found in the digestive tract.
Are neuroendocrine tumors always cancerous? ›About neuroendocrine tumours
NETs are tumours (abnormal growths) that develop in the cells of the neuroendocrine system. NETs can be malignant (cancerous) or benign (non-cancerous) and often – but not always – grow slowly. There are a number of different types of NET, depending on the specific cells affected.
Compared with more common malignant tumors, neuroendocrine tumors are slow-growing but can produce amino acids that cause severe symptoms. Aggressive therapy is recommended to lessen the severity of symptoms or to prevent possible harm to the liver. The portal for UPMC Cole patients receiving inpatient care.
What is the most common neuroendocrine tumor? ›Pancreatic neuroendocrine tumors (PNETs), a group of endocrine tumors arising in the pancreas, are among the most common neuroendocrine tumors (NETs). Functioning PNETs include insulinoma, gastrinoma, VIPoma, glucagonoma, and others that produce specific hormonal hypersecretion syndromes.
What is another name for chromogranin A? ›Chromogranin A or parathyroid secretory protein 1 (gene name CHGA) is a member of the granin family of neuroendocrine secretory proteins.
Is chromogranin A serum marker for neuroendocrine carcinoma? ›CHROMOGRANIN A (CgA) is a protein that is present in the secretory dense core granules of neuroendocrine tissues (1). It is widely used as an immunohistochemical marker of neuroendocrine tumors.
What foods to avoid for chromogranin test? ›
1. Patients should not eat avocados, bananas, butternuts, cantaloupe, dates, eggplant, grapefruit, hickory nuts, honeydew melon, kiwifruit, melon, nuts, pecans, pineapple, plantains, plums, tomatoes, or walnuts, which are high in serotonin for 48 hours before and during collection.
Should I fast for a chromogranin test? ›These types of tests measure the amount of gastrin, sugar, VIP, or somatostatin in the blood. Patients may need to fast for at least 8 hours for these tests.
What are the biomarkers for carcinoid? ›Laboratory diagnosis of carcinoid tumors depends on the identification of the characteristic biomarkers of the disease. Measurement of biogenic amines levels (eg, serotonin, 5-HT, catecholamines, histamine) and its metabolites in the platelets, plasma, and urine of patients can be helpful in diagnosis.
What does elevated 5-HIAA mean? ›Higher levels of 5-HIAA may mean you have: Carcinoid tumors. Noncarcinoid tumors. Cystic fibrosis. Malabsorption.
What cancers does CA-125 detect? ›If you have ovarian, endometrial, peritoneal or fallopian tube cancer, your provider may recommend a CA 125 test on a regular basis to monitor your condition and treatment.
What blood test shows neuroendocrine tumor? ›Chromogranin (CgA test)
The chromogranin A (CgA) test measures the amount of CgA in the blood. CgA is a protein that many neuroendocrine cells produce. But CgA can also be raised for other reasons that are not related to cancer.