Diagnostic accuracy of chromogranin A and calcitonin precursors measurements for the discrimination of ectopic ACTH secretion from Cushing's disease

Authors

Marina S. Zemskova, National Institute of Child Health and Human Development (NICHD)
Eric S. Nylen, The George Washington University
Nicholas J. Patronas, National Institutes of Health (NIH)
Edward H. Oldfield, National Institute of Neurological Disorders and Stroke (NINDS)
Kenneth L. Becker, The George Washington University
Lynnette K. Nieman, National Institute of Child Health and Human Development (NICHD)

Document Type

Journal Article

Publication Date

1-1-2009

Journal

Journal of Clinical Endocrinology and Metabolism

Volume

94

Issue

8

DOI

10.1210/jc.2009-0604

Abstract

Context: Inferior petrosal sinus sampling (IPSS) best discriminates between the two causes of ACTH-dependent Cushing's syndrome, Cushing's disease (CD) and ectopic ACTH secretion (EAS). However, when sampling is not available, adjunctive diagnostic tests might be helpful. Neuroendocrine tumors may secrete chromogranin A (CgA), calcitonin (CT), procalcitonin (ProCT), a fragment of the amino terminus of procalcitonin (NProCT), and/or ACTH. Objective: The aim of the study was to evaluate the ability of serum CgA, CT, ProCT, or NProCT values to distinguish CD from EAS. Design and Setting: We conducted a prospective pilot study at a clinical research center. Subjects and Methods: Serum ProCT, NProCT, and CgA were measured in six patients with occult EAS diagnosed by IPSS, 25 CD patients, and 11 patients with histologically proven EAS. Results: Nine EAS patients (53%) had at least one value above the reference range, including CgA alone (n = 4), ProCT alone (n = 3), CgA and ProCT (n = 1), and NProCT and ProCT (n = 1). Of nine (36%) CD patients with one or two abnormal values, seven had increased ProCT only, one had increased NProCT only, and one had increased CgA and ProCT. CgA had a positive predictive value of 83% and a negative predictive value of 70% for the diagnosis of EAS; other markers showed less discrimination. On pituitary magnetic resonance imaging, no EAS patient had an abnormality, whereas 21 of 25 patients with CD had a mass. Conclusion: These preliminary results suggest that an abnormal CgA and normal pituitary magnetic resonance imaging favor the diagnosis of EAS, but normal tumor markers do not exclude the diagnosis. Copyright © 2009 by The Endocrine Society.

APA Citation

Zemskova, M., Nylen, E., Patronas, N., Oldfield, E., Becker, K., & Nieman, L. (2009). Diagnostic accuracy of chromogranin A and calcitonin precursors measurements for the discrimination of ectopic ACTH secretion from Cushing's disease. Journal of Clinical Endocrinology and Metabolism, 94 (8). http://dx.doi.org/10.1210/jc.2009-0604