title: Second-line tests in the differential diagnosis of ACTH-dependent Cushing's syndrome.
abstract: BACKGROUND
  Diagnosing Cushing's syndrome (CS) can be a challenge, especially in ACTH-dependent CS, when it comes to detecting the origin of ACTH secretion.
  
  
  METHODS
  Retrospective data were collected on 170 patients with ACTH-dependent CS (149 CD, 21 EAS) referring to two endocrinology units, focusing on three non-invasive tests: dexamethasone 8 mg overnight challenge (HDDST); corticotrophin-releasing hormone (CRH) assay and the desmopressin (DDAVP) test.
  
  
  RESULTS
  Patients with EAS were slightly older and had higher ACTH, serum and urinary cortisol levels than patients with CD (p < 0.01). CD patients had a stronger ACTH and cortisol response after CRH injection (p < 0.0001), and a more pronounced reduction in cortisol levels after HDDST (p < 0.0001). A threshold percentage ACTH increase after CRH stimulation of 72.4 % was able to identify CD with a sensitivity (SE) of 76 % (95 % CI 68-83) and a specificity (SP) of 100 % (95 % CI 83-100). As for HDDST, a cortisol suppression >52.7 % below the basal level suggested a pituitary origin with a SE of 88 % (95 % CI 81-93) and a SP of 90 % (95 % CI 68-99). There were no cases of EAS with positive responses to both these tests. Increases in ACTH and cortisol levels after the DDAVP test were also higher in CD than in EAS (p < 0.01), though the SE and SP were lower.
  
  
  CONCLUSIONS
  Patients with CD showed a stronger response to HDDST and CRH, and the adopted cut-offs showed a good SE and SP in discriminating them from patients with EAS. Concordant tests indicated CD when positive, whereas no response to either test was highly suggestive of EAS. The DDAVP test was of limited utility in the diagnostic phase. In conclusion, the choice of tests may play an important part in the differential diagnosis of ACTH-dependent CS.
authors.affiliation: Endocrinology Unit, Department of Medicine DIMED, University of Padova, Via Ospedale Civile, 105, 35128, Padua, Italy. mattiabarbot@alice.it.
authors.forename: Mattia
authors.initials: M
authors.lastname: Barbot
authors.affiliation: Endocrinology Unit, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Trementino
authors.affiliation: Endocrinology Unit, Department of Medicine DIMED, University of Padova, Via Ospedale Civile, 105, 35128, Padua, Italy.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Zilio
authors.affiliation: Endocrinology Unit, Department of Medicine DIMED, University of Padova, Via Ospedale Civile, 105, 35128, Padua, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Ceccato
authors.affiliation: Endocrinology Unit, Department of Medicine DIMED, University of Padova, Via Ospedale Civile, 105, 35128, Padua, Italy.
authors.forename: Nora
authors.initials: N
authors.lastname: Albiger
authors.affiliation: Endocrinology Unit, Department of Medicine DIMED, University of Padova, Via Ospedale Civile, 105, 35128, Padua, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Daniele
authors.affiliation: Biostatistics, Epidemiology and Public Health Unit, Department of Cardiac, Thoracic and Vascular Sciences, University Hospital, Padua, Italy.
authors.forename: Anna Chiara
authors.initials: AC
authors.lastname: Frigo
authors.affiliation: Neuroradiology Unit, University Hospital, Padua, Italy.
authors.forename: Rodica
authors.initials: R
authors.lastname: Mardari
authors.affiliation: Neuroradiology Unit, University Hospital, Padua, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rolma
authors.affiliation: Endocrinology Unit, Department of Medicine DIMED, University of Padova, Via Ospedale Civile, 105, 35128, Padua, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Boscaro
authors.affiliation: Endocrinology Unit, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Arnaldi
authors.affiliation: Endocrinology Unit, Department of Medicine DIMED, University of Padova, Via Ospedale Civile, 105, 35128, Padua, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Scaroni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003346:Corticotropin-Releasing Hormone; D003480:Cushing Syndrome / Q000175:diagnosis*; D003894:Deamino Arginine Vasopressin; D003907:Dexamethasone; D003940:Diagnostic Techniques, Endocrine; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone; D003894:Deamino Arginine Vasopressin
keywords: CRH test; Cushing’s disease; Cushing’s syndrome; Desmopressin test; Dexamethasone test; Ectopic Cushing’s syndrome; MRI