title: Urine free cortisol in the high-dose dexamethasone suppression test for the differential diagnosis of the Cushing syndrome.
abstract: OBJECTIVE
  To develop criteria for interpreting the high-dose dexamethasone suppression test using urine free cortisol as an end point for the differential diagnosis of the Cushing syndrome.
  
  
  METHODS
  Retrospective review.
  
  
  METHODS
  Inpatient research ward.
  
  
  METHODS
  Patients (118) with surgically confirmed causes of the Cushing syndrome: 94 with pituitary disease, 14 with primary adrenal disease, and 10 with ectopic adrenocorticotropic hormone (ACTH) secretion.
  
  
  METHODS
  The sensitivity, specificity, and diagnostic accuracy were determined for the high-dose dexamethasone suppression test using urine free cortisol and using 17-hydroxysteroid excretion. For each analysis, patients with pituitary disease were considered to be "diseased" and patients with nonpituitary disease were considered to be "non-diseased". The level of suppression that gave 100% specificity was determined for each steroid.
  
  
  RESULTS
  The accuracy of urine free cortisol when used as an end point in the high-dose dexamethasone suppression test was equivalent to that of 17-hydroxysteroid excretion. At all levels of sensitivity and specificity, however, the degree of suppression of urine free cortisol used for the diagnosis of pituitary disease was greater than that of 17-hydroxysteroid excretion. The likelihood ratios for pituitary disease based on urine free cortisol suppression of greater than 50%, of greater than 80%, and of greater than 90% were 4.2, 10.1, and "infinite," respectively. Suppression of urine free cortisol greater than 90% or suppression of 17-hydroxysteroid excretion greater than 64% was associated with 100% specificity. When these criteria were combined, the percentage of correct predictions (102 of 118 [86%; 95% CI, 78% to 92%]) was higher than that obtained using either steroid alone (89 of 118 [75%; CI, 65% to 83%]) (P = 0.009) and higher than that obtained using the traditional criterion of 50% suppression for 17-hydroxysteroid excretion (95 of 118 [80%; CI, 71% to 87%]) (P = 0.016).
  
  
  CONCLUSIONS
  In the high-dose dexamethasone suppression test, the degree of suppression of urine free cortisol used for the diagnosis of pituitary disease is greater than that traditionally used for 17-hydroxysteroid excretion. The diagnostic performance of the test is improved by measuring both urine free cortisol and 17-hydroxysteroid excretion and by requiring greater suppression of both steroids.
authors.affiliation: National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors.forename: M R
authors.initials: MR
authors.lastname: Flack
authors.forename: E H
authors.initials: EH
authors.lastname: Oldfield
authors.forename: G B
authors.initials: GB
authors.lastname: Cutler
authors.forename: M H
authors.initials: MH
authors.lastname: Zweig
authors.forename: J D
authors.initials: JD
authors.lastname: Malley
authors.forename: G P
authors.initials: GP
authors.lastname: Chrousos
authors.forename: D L
authors.initials: DL
authors.lastname: Loriaux
authors.forename: L K
authors.initials: LK
authors.lastname: Nieman
mesh_terms: D015065:17-Hydroxycorticosteroids / Q000652:urine; D003480:Cushing Syndrome / Q000209:etiology* / Q000652:urine; D003907:Dexamethasone / Q000008:administration & dosage; D003937:Diagnosis, Differential; D006801:Humans; D006854:Hydrocortisone / Q000652:urine*; D016013:Likelihood Functions; D010900:Pituitary Diseases / Q000175:diagnosis; D011237:Predictive Value of Tests; D012372:ROC Curve; D012189:Retrospective Studies
chemical_list: D015065:17-Hydroxycorticosteroids; D003907:Dexamethasone; D006854:Hydrocortisone