Friday, June 5, 2009

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


Marina S. Zemskova, Eric S. Nylen, Nicholas J. Patronas, Edward H. Oldfield, Kenneth L. Becker,  and Lynnette K. Nieman*

The Program in Reproductive and Adult Endocrinology, The Eunice Shriver Kennedy National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA; Veterans Affairs Medical Center and George Washington University, Washington, DC, USA; Department of Diagnostic Radiology, Warren O. Hatfield Clinical Research Center, National Institutes of Health, Bethesda, MD, USA; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

* To whom correspondence should be addressed. E-mail:

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: To evaluate the ability of serum CgA, CT, ProCT or NProCT values to distinguish CD from EAS.

Design: Prospective pilot study

Settings: 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 eleven 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 MRI, no EAS patient had an abnormality while 21/25 patients with CD had a mass.

Conclusion: These preliminary results suggest that an abnormal CgA and normal pituitary MRI favor the diagnosis of EAS, but normal tumor markers do not exclude the diagnosis.

Key words: Cushing's syndrome • neuroendocrine tumors • chromogranin A • calcitonin precursors • diagnostic accuracy • sensitivity and specificity