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


METHODS
We conducted a prospective pilot study at a clinical research center.


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.


CONCLUSIONS
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.
Zemskova
Marina S
MS
The Program in Reproductive and Adult Endocrinology, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892-1109, USA.
Nylen
Eric S
ES
Patronas
Nicholas J
NJ
Oldfield
Edward H
EH
Becker
Kenneth L
KL
Nieman
Lynnette K
LK
D000182:ACTH Syndrome, Ectopic / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D053379:Chromogranin A / Q000097:blood*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010865:Pilot Projects; D047748:Pituitary ACTH Hypersecretion / Q000097:blood / Q000175:diagnosis*; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; C000606589:CALCA protein, human; D053379:Chromogranin A; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide; D006854:Hydrocortisone