title: Predicting late recurrence in surgically treated patients with Cushing's disease.
abstract: OBJECTIVE
  Cushing's disease (CD) has an uncertain prognosis because patients achieving remission after transsphenoidal pituitary neurosurgery (TSS) may relapse. We aimed to identify factors predicting relapse, focusing on desmopressin (DDAVP) and corticotropin-releasing hormone (CRH) tests after surgery.
  
  
  METHODS
  Fifty-seven patients with CD (mean age 36 years) after TSS experienced remission (24 cases), late relapse (LR) (15 cases), or persistent disease (18 cases).
  
  
  RESULTS
  The median time to relapse was 40 months. ACTH levels increased after both DDAVP and CRH stimulation, with a significantly higher response in the late recurrence group, showing this to be an indicator of increased risk of relapse. In the logistic regression model, a rise in ACTH >9 pg/ml after DDAVP and >36·7 pg/ml after CRH showed a sensitivity of 93% and 73%, respectively, a specificity of 82% and 76% in LR group. The area under the curve was 0·91 for DDAVP, 0·80 for CRH and 0·95 for DDAVP+CRH test, i.e. the combined tests performed better than each test alone, but not to a statistically significant degree. A response to both tests resulted in a positive predictive value (PPV) of 100%, while no response to either test in a negative predictive value (NPV) of 100%.
  
  
  CONCLUSIONS
  ACTH hyper-responsiveness to DDAVP stimulation proved a valuable indicator of relapsing patients with high sensitivity and specificity; in selected cases when a clear high increment of ACTH level is not evident, the CRH test might be used as additional tool to confirm the risk of future relapses.
authors.affiliation: Endocrinology Unit, Department of Medicine DIMED, University of Padova, Padova, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Barbot
authors.forename: Nora
authors.initials: N
authors.lastname: Albiger
authors.forename: Stavroula
authors.initials: S
authors.lastname: Koutroumpi
authors.forename: Filippo
authors.initials: F
authors.lastname: Ceccato
authors.forename: Anna C
authors.initials: AC
authors.lastname: Frigo
authors.forename: Renzo
authors.initials: R
authors.lastname: Manara
authors.forename: Ambrogio
authors.initials: A
authors.lastname: Fassina
authors.forename: Marina P
authors.initials: MP
authors.lastname: Gardiman
authors.forename: Massimo
authors.initials: M
authors.lastname: Scanarini
authors.forename: Franco
authors.initials: F
authors.lastname: Mantero
authors.forename: Carla
authors.initials: C
authors.lastname: Scaroni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D003198:Computer Simulation; D003346:Corticotropin-Releasing Hormone / Q000097:blood*; D003894:Deamino Arginine Vasopressin / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery*; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003346:Corticotropin-Releasing Hormone; D003894:Deamino Arginine Vasopressin