Postoperative Day 1 Morning Cortisol Value as a Biomarker to Predict Long-term Remission of Cushing Disease

J Clin Endocrinol Metab. 2021 Jan 1;106(1):e94-e102. doi: 10.1210/clinem/dgaa773.


Context: Recurrence of Cushing disease (CD) can occur even decades after surgery. Biomarkers to predict recurrence of CD after surgery have been studied but are inconclusive.

Objective: The aim of our study was to identify specific biomarkers that can predict long-term remission after neurosurgery.

Design: Identification of specific biomarkers to predict long-term remission of CD was performed by logistic regression analysis followed by Kaplan-Meier survival analysis, using recurrence as the dependent variable.

Setting: A total of 260 patients with CD identified from our institutional research patient data registry search tool and from patients who presented to our longitudinal multidisciplinary clinic between May 2008 and May 2018 underwent statistical analysis.

Interventions: Data on clinical features, neuro-imaging study, pathology, biochemistry, and treatments were collected by reviewing digital chart records.

Main outcome measure: Postoperative cortisol as a biomarker to predict long-term remission after surgical treatment for CD.

Results: By logistic regression analysis, postoperative day 1 (POD1) morning (5-10 am) serum cortisol, female sex, and proliferative index had significant association with CD recurrence (odds ratio [OR] = 1.025, 95% CI: 1.002-1.048, P = .032). In contrast, the postoperative nadir cortisol (OR = 1.081, 95% CI: 0.989-1.181, P = .086), urinary free cortisol (OR = 1.032, 95% CI: 0.994-1.07, P = .098), and late night salivary cortisol (OR = 1.383, 95% CI: 0.841-2.274, P = .201) had no significant correlation with recurrence. A significant association between POD1 morning serum cortisol and long-term CD remission was verified by Kaplan-Meier analysis when using POD1 morning serum cortisol <5 μg/dL as the cut-off.

Conclusions: The POD1 morning serum cortisol level has a significant association with CD recurrence.

Keywords: Cushing disease; biomarker; corticotroph adenoma; corticotroph hyperplasia; cortisol; remission.

MeSH terms

  • ACTH-Secreting Pituitary Adenoma / complications
  • ACTH-Secreting Pituitary Adenoma / diagnosis
  • ACTH-Secreting Pituitary Adenoma / metabolism
  • ACTH-Secreting Pituitary Adenoma / surgery
  • Adenoma / complications
  • Adenoma / diagnosis
  • Adenoma / metabolism
  • Adenoma / surgery
  • Adrenocorticotropic Hormone / blood
  • Adult
  • Biomarkers / blood
  • Circadian Rhythm
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Hydrocortisone / analysis
  • Hydrocortisone / blood*
  • Male
  • Middle Aged
  • Neurosurgical Procedures
  • Pituitary ACTH Hypersecretion / blood
  • Pituitary ACTH Hypersecretion / diagnosis*
  • Pituitary ACTH Hypersecretion / etiology
  • Pituitary ACTH Hypersecretion / surgery*
  • Postoperative Period
  • Predictive Value of Tests
  • Prognosis
  • Recurrence
  • Remission Induction
  • Retrospective Studies
  • Treatment Outcome


  • Biomarkers
  • Adrenocorticotropic Hormone
  • Hydrocortisone