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23238 Chromogranin A, Serum (CGAK)

Chromogranin A, Serum (CGAK)
Test Code: CHRASO
Useful For
Follow-up or surveillance of patients with known or treated carcinoid tumors
 
Adjunct in the diagnosis of carcinoid tumors
 
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
Specimen Requirements
Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
Serum​ ​Serum Separator Tube (SST) ​Red Top Tube (RTT) ​0.5 mL ​0.2 mL
Collection Processing Instructions

​Proton pump inhibitor drugs should be discontinued for at least 2 weeks before collection.

Centrifuge and aliquot serum into plastic vial.  Do NOT submit in original tube. 

Specimen Stability Information
Specimen Type Temperature Time
​Serum ​ ​ ​Frozen (preferred) 90 days
​Ambient​7 days
​Refrigerated​24 hours
Rejection Criteria
Gross Hemolysis
Performing Laboratory Information
Performing Location Day(s) Test Performed Report Available Methodology/Instrumentation
​Mayo Clinic Laboratories Monday through Saturday​ ​1 to 3 days
Immunofluorescent Assay (IFA)​
Reference Lab
Test 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 (MTC), some pituitary tumors, functioning and nonfunctioning islet cell tumors and other amine precursor uptake and decarboxylation (APUD) 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: 5-HT) 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 urine 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)
Reference Range Information
<93 ng/mL
Reference values apply to all ages.
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 is 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, which 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)
Outreach CPTs
CPT Modifier
(if needed)
Quantity Description Comments
86316​
Ordering Applications
Ordering Application Description
​Centricity ​Chromogranin A, Serum (CGAK)
​Cerner ​Chromogranin A (83559)
If the ordering application you are looking for is not listed, contact your local laboratory for assistance.
Specimen Requirements
Specimen Type Preferred Container/Tube Acceptable Container/Tube Specimen Volume Specimen Minimum Volume
(allows for 1 repeat)
Pediatric Minimum Volume
(no repeat)
Serum​ ​Serum Separator Tube (SST) ​Red Top Tube (RTT) ​0.5 mL ​0.2 mL
Collection Processing

​Proton pump inhibitor drugs should be discontinued for at least 2 weeks before collection.

Centrifuge and aliquot serum into plastic vial.  Do NOT submit in original tube. 

Specimen Stability Information
Specimen Type Temperature Time
​Serum ​ ​ ​Frozen (preferred) 90 days
​Ambient​7 days
​Refrigerated​24 hours
Rejection Criteria
Gross Hemolysis
Useful For
Follow-up or surveillance of patients with known or treated carcinoid tumors
 
Adjunct in the diagnosis of carcinoid tumors
 
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
Reference Range Information
<93 ng/mL
Reference values apply to all ages.
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 is 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, which 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)
For more information visit:
Performing Laboratory Information
Performing Location Day(s) Test Performed Report Available Methodology/Instrumentation
​Mayo Clinic Laboratories Monday through Saturday​ ​1 to 3 days
Immunofluorescent Assay (IFA)​
Reference Lab
For billing questions, see Contacts
Outreach CPTs
CPT Modifier
(if needed)
Quantity Description Comments
86316​
For most current information refer to the Marshfield Laboratory online reference manual.