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: NiemanL@nih.gov.
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