Predicting late recurrence in surgically treated patients with Cushing's disease

Clin Endocrinol (Oxf). 2013 Sep;79(3):394-401. doi: 10.1111/cen.12133. Epub 2013 May 6.

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.

Materials and 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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Area Under Curve
  • Computer Simulation
  • Corticotropin-Releasing Hormone / blood*
  • Deamino Arginine Vasopressin / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pituitary ACTH Hypersecretion / diagnosis*
  • Pituitary ACTH Hypersecretion / pathology
  • Pituitary ACTH Hypersecretion / surgery*
  • Predictive Value of Tests
  • Prognosis
  • Recurrence
  • Remission Induction
  • Treatment Outcome
  • Young Adult

Substances

  • Corticotropin-Releasing Hormone
  • Deamino Arginine Vasopressin