Management of Neuroendocrine Tumors: Current and Future Therapies

Kjell E Öberg


Expert Rev Endocrinol Metab. 2011;6(1):49-62. 

In This Article

Biochemical Markers

A variety of generalized and specific biochemical tests are available for symptomatic patients, which can assist with the initial diagnosis and assessment of required treatment, and may offer prognostic information.[6] The most common tests are discusssed in the following sections.

Chromogranin A

Chromogranin A (CgA) is present in the chromaffin granules of neuroendocrine cells and measurement via a blood test can be used to diagnose both functioning and nonfunctioning NETs. Recent studies have suggested that CgA should be the primary biomarker used for the diagnosis of NETs as levels correlate with tumor burden,[7] and provide a more sensitive assessment compared with other biomarkers.[8,9] In addition, early CgA response (normalization or ≥30% decrease by week 4) may correlate with improved progression-free survival (PFS).[10] However, CgA levels are nonspecific as they are elevated in a number of different NETs[11] and in other unrelated conditions. CgA is applied both as a circulating and tissue marker.


Ki-67 is a protein found in the cell nucleus during cell division; its assessment as a marker of tumor proliferation should be considered in patients with NETs.[12] Lower proliferation as indicated by low Ki-67 levels correlates with longer survival.[13]

5-hydroxyindoleacetic Acid

5-hydroxyindoleacetic acid (5-HIAA) is a serotonin metabolite used to identify certain types of functioning NETs; measurement of 5-HIAA has a sensitivity of 73% and a specificity of 100% in predicting the presence of a midgut NET.[12] Certain foods and drugs can affect the urinary excretion of 5-HIAA if taken just before urine collection, which can lead to false positive or negative results.

Other specific hormones related to clinical syndromes are gastrin for Zollinger–Ellison syndrome, insulin/proinsulin for hypoglycemia symptoms, glucagon for glucagonomas and vasoactive intestinal peptide (VIP) for VIP-omas.


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