title: Human corticotropin releasing hormone test performance in the differential diagnosis between Cushing's disease and pseudo-Cushing state is enhanced by combined ACTH and cortisol analysis.
abstract: OBJECTIVE
  Corticotropin releasing hormone (CRH) test does not reliably distinguish Cushing's disease (CD) from normality or pseudo-Cushing state (PC). We assessed whether this could be achieved with a novel approach while preserving the ability of the test to distinguish CD from ectopic ACTH syndrome (EAS). Design Retrospective/prospective study.
  
  
  METHODS
  We studied 51 subjects with CD, 7 with EAS, 26 with PC, and 31 controls (CT). Human CRH (hCRH) test was performed at 0830 h by measuring plasma ACTH and serum cortisol at -15, 0, 15, 30, 45, 60, 90, and 120 min.
  
  
  RESULTS
  The area under the curve-ACTH exhibited a significant negative correlation with baseline serum cortisol in CT and PC, but not in CD or EAS patients. ACTH response to hCRH was blunted in PC compared with CT, whereas peak serum cortisol was higher in PC than in CT subjects. These findings suggested that ACTH-dependent Cushing's syndrome can be diagnosed by the presence of two hCRH test parameters and excluded if either or both are absent. Application of i) basal serum cortisol >12 microg/dl and peak plasma ACTH >54 pg/ml, or ii) peak serum cortisol >21 microg/dl and peak plasma ACTH >45 pg/ml, had 91.3% (95% confidence intervals (CI) 81-97.1) and 94.8% (CI 85.6-98.9) sensitivity and 98.2% (CI 90.6-99.9) and 91.2% (CI 80.7-97) specificity respectively, in diagnosing ACTH-dependent Cushing's syndrome. The >14% serum cortisol increase from mean baseline values to the mean of 15 and 30 min values in patients who were positive for the test completely discriminated between CD and EAS.
  
  
  CONCLUSIONS
  Simultaneous plasma ACTH and serum cortisol analysis enables the hCRH test to distinguish CD from PC and from normality, while preserving its ability to discriminate CD from EAS.
authors.affiliation: Division of Endocrinology, Polytechnic University of Marche, 60100 Ancona, Italy Social Gerontology Unit, Research Department, INRCA (Italian National Institute on Ageing), 60100 Ancona, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Arnaldi
authors.forename: Giacomo
authors.initials: G
authors.lastname: Tirabassi
authors.forename: Roberta
authors.initials: R
authors.lastname: Papa
authors.forename: Giorgio
authors.initials: G
authors.lastname: Furlani
authors.forename: Laura
authors.initials: L
authors.lastname: Trementino
authors.forename: Marina
authors.initials: M
authors.lastname: Cardinaletti
authors.forename: Emanuela
authors.initials: E
authors.lastname: Faloia
authors.forename: Marco
authors.initials: M
authors.lastname: Boscaro