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)