title: The dexamethasone-suppressed corticotropin-releasing hormone stimulation test and the desmopressin test to distinguish Cushing's syndrome from pseudo-Cushing's states.
abstract: OBJECTIVE
  Cushing's syndrome (CS), when fully expressed, is easily diagnosed. Mild cases, however, may require careful distinction from pseudo-Cushing's states as may occur in depression, alcoholism, polycystic ovary disease and visceral obesity. The aim of the present study is a reappraisal of the diagnostic accuracy of the two tests most commonly used to differentiate CS from pseudo-Cushing's: corticotropin-releasing hormone (CRH) stimulation after low dose dexamethasone administration and desmopressin stimulation.
  
  
  METHODS
  The study population comprised 32 patients with CS and 23 with pseudo-Cushing's evaluated retrospectively.
  
  
  METHODS
  Urinary free cortisol (UFC), serum cortisol at midnight and after low dose dexamethasone (1 mg overnight and 2 mg over two days) were measured. Further, patients were tested with dexamethasone + CRH and desmopressin and the diagnostic performances of the two tests were compared in the entire series as well as in patients with mild hypercortisolism only (i.e. UFC < 690 nmol/24 h).
  
  
  RESULTS
  As expected, measurement of UFC, assessment of cortisol rhythmicity and inhibition after 1 mg/2 mg dexamethasone failed to clearly classify patients with pseudo-Cushing's. Administration of CRH following 2-mg dexamethasone achieved 100% sensitivity but 62.5% specificity. Conversely, desmopressin testing correctly classified all but two patients with pseudo-Cushing's (90% specificity) with 81.5% sensitivity. Diagnostic accuracy was comparable in the subgroup with mild hypercortisolism (21 CS, all 23 pseudo-Cushing's patients). Desmopressin offered an incremental diagnostic effectiveness of 35.8/million inhabitants compared with dexamethasone + CRH as a second-line test.
  
  
  CONCLUSIONS
  Neither of the two tests guarantees absolute diagnostic accuracy. The specificity of dexamethasone + CRH is less brilliant than previously reported and appears to be inferior to desmopressin stimulation. The greatest diagnostic effectiveness results from the low-dose dexamethasone test combined with the desmopressin test. Skilful use of dynamic testing and balanced clinical judgement are necessary to distinguish between Cushing's syndrome and pseudo-Cushing's.
authors.affiliation: Department of Endocrinology, University of Milan, Ospedale San Luca, Istituto Auxologico Italiano, IRCCS, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pecori Giraldi
authors.forename: Rosario
authors.initials: R
authors.lastname: Pivonello
authors.forename: Alberto Giacinto
authors.initials: AG
authors.lastname: Ambrogio
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: De Martino
authors.forename: Martina
authors.initials: M
authors.lastname: De Martin
authors.forename: Massimo
authors.initials: M
authors.lastname: Scacchi
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.forename: Paola Maria
authors.initials: PM
authors.lastname: Toja
authors.forename: Gaetano
authors.initials: G
authors.lastname: Lombardi
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavagnini
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D016009:Chi-Square Distribution; D002648:Child; D003346:Corticotropin-Releasing Hormone / Q000097:blood*; D003480:Cushing Syndrome / Q000175:diagnosis*; D003894:Deamino Arginine Vasopressin; D003907:Dexamethasone / Q000097:blood; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D008297:Male; D008875:Middle Aged; D010900:Pituitary Diseases / Q000175:diagnosis; D010901:Pituitary Function Tests; D012680:Sensitivity and Specificity
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003894:Deamino Arginine Vasopressin; D006854:Hydrocortisone