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The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 8 2622-2628
Copyright © 1997 by The Endocrine Society

Experimental Studies

Chromogranin A as Serum Marker for Neuroendocrine Neoplasia: Comparison with Neuron-Specific Enolase and the {alpha}-Subunit of Glycoprotein Hormones

Frank R. E. Nobels, Dik J. Kwekkeboom, Willy Coopmans, Christiaan H. H. Schoenmakers, Jan Lindemans, Wouter W. De Herder, Eric P. Krenning, Roger Bouillon and Steven W. J. Lamberts

Departments of Medicine (F.N., W.D.H., S.L.), Nuclear Medicine (D.K., E.K.), and Clinical Laboratory (C.S., J.L.), University Hospital Dijkzigt, Rotterdam, The Netherlands; and the Laboratory of Experimental Medicine and Endocrinology, University Hospital Gasthuisberg (W.C., R.B.), Leuven, Belgium

Address all correspondence and requests for reprints to: Dr. F. Nobels, Department of Endocrinology, Onze Lieve Vrouw Hospital, 164 Moorselbaan, 9300 Aalst, Belgium.

Chromogranin A (CgA) is gaining acceptance as a serum marker of neuroendocrine tumors. Its specificity in differentiating between neuroendocrine and nonneuroendocrine tumors, its sensitivity to detect small tumors, and its clinical value, compared with other neuroendocrine markers, have not clearly been defined, however. The objectives of this study were to evaluate the clinical usefulness of CgA as neuroendocrine serum marker. Serum levels of CgA, neuron-specific enolase (NSE), and the {alpha}-subunit of glycoprotein hormones ({alpha}-SU) were determined in 211 patients with neuroendocrine tumors and 180 control subjects with nonendocrine tumors. The concentrations of CgA, NSE, and {alpha}-SU were elevated in 50%, 43%, and 24% of patients with neuroendocrine tumors, respectively. Serum CgA was most frequently increased in subjects with gastrinomas (100%), pheochromocytomas (89%), carcinoid tumors (80%), nonfunctioning tumors of the endocrine pancreas (69%), and medullary thyroid carcinomas (50%). The highest levels were observed in subjects with carcinoid tumors. NSE was most frequently elevated in patients with small cell lung carcinoma (74%), and {alpha}-SU was most frequently elevated in patients with carcinoid tumors (39%). Most subjects with elevated {alpha}-SU levels also had elevated CgA concentrations. A significant positive relationship was demonstrated between the tumor load and serum CgA levels (P < 0.01, by {chi}2 test). Elevated concentrations of CgA, NSE, and {alpha}-SU were present in, respectively, 7%, 35%, and 15% of control subjects. Markedly elevated serum levels of CgA, exceeding 300 µg/L, were observed in only 2% of control patients (n = 3) compared to 40% of patients with neuroendocrine tumors (n = 76). We conclude that CgA is the best general neuroendocrine serum marker available. It has the highest specificity for the detection of neuroendocrine tumors compared to the other neuroendocrine markers, NSE and {alpha}-SU. Elevated levels are strongly correlated with tumor volume; therefore, small tumors may go undetected. Although its specificity cannot compete with that of the specific hormonal secretion products of most neuroendocrine tumors, it can have useful clinical applications in subjects with neuroendocrine tumors for whom either no marker is available or the marker is inconvenient for routine clinical use.




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