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Chromogranin A

Chromogranin A is a member of the granin family of proteins that are present within the secretory granules of cells in endocrine, neuroendocrine, and nerve tissues. Chromogranin A is a useful diagnostic biomarker for neuroendocrine tumors such as carcinoid tumors, pheochromocytoma and neuroblastoma.

Serum chromogranin A and urine 5-hydroxyindolacetic acid (5-HIAA) are considered to be the most useful biochemical markers for carcinoid tumors. Carcinoid tumors almost always secrete chromogranin A in addition to other substances (See Carcinoid Syndrome article). Chromogranin A is elevated to several times the upper limit of the reference range in 90% of patients with carcinoid syndrome. Chromogranin A is particularly useful for diagnosing mid and hindgut carcinoid tumors, since they may not secrete serotonin and 5-HIAA.

Chromogranin A may be used to detect residual or recurrent disease in treated patients. Guidelines recommend measurements of chromogranin A every 3 to 12 months to monitor recurrence of midgut carcinoids. Patients with foregut tumors can also be monitored with chromogranin A measurements, if they had detectable levels at initial diagnosis. Chromogranin A is the only biomarker to monitor hindgut carcinoid tumor recurrence because they do not secrete serotonin. A 40% to 50% change in serum chromogranin A concentrations should be considered clinically significant.

Chromogranin A is significantly elevated in pheochromocytoma and neuroblastoma and may be helpful in diagnosing these tumors in patients that have only mild elevations of catecholamines and metanephrines.

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.

Atrophic gastritis and pernicious anemia are associated with elevations of chromogranin A due to gastric achlorhydria and lack of feedback inhibition of gastrin production. Chromogranin A is normally cleared from the circulation by a combination of hepatic metabolism and renal excretion. Hepatic failure causes minor elevations of chromogranin A. Renal impairment can significantly elevate chromogranin A.

Proton pump inhibitors such as omeprazole significantly elevate serum chromogranin A levels to many times above the upper limit of the reference range. Proton pump inhibitor drugs should be discontinued for at least 2 weeks before collection. H2-receptor antagonists at moderate doses do not elevate chromogranin A.

There is no universal calibration standard for serum chromogranin A assays. Different laboratories may have different reference ranges. Reference range is 0-95 ng/mL for all age groups.

A hook effect may occur at extremely high chromogranin levels resulting in falsely decreased values.

Specimen requirement is a red top tube of blood.

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