Development of Machine Learning Models for Predicting Postoperative Delayed Remission in Patients With Cushing's Disease

J Clin Endocrinol Metab. 2021 Jan 1;106(1):e217-e231. doi: 10.1210/clinem/dgaa698.


Context: Postoperative hypercortisolemia mandates further therapy in patients with Cushing's disease (CD). Delayed remission (DR) is defined as not achieving postoperative immediate remission (IR), but having spontaneous remission during long-term follow-up.

Objective: We aimed to develop and validate machine learning (ML) models for predicting DR in non-IR patients with CD.

Methods: We enrolled 201 CD patients, and randomly divided them into training and test datasets. We then used the recursive feature elimination (RFE) algorithm to select features and applied 5 ML algorithms to construct DR prediction models. We used permutation importance and local interpretable model-agnostic explanation (LIME) algorithms to determine the importance of the selected features and interpret the ML models.

Results: Eighty-eight (43.8%) of the 201 CD patients met the criteria for DR. Overall, patients who were younger, had a low body mass index, a Knosp grade of III-IV, and a tumor not found by pathological examination tended to achieve a lower rate of DR. After RFE feature selection, the Adaboost model, which comprised 18 features, had the greatest discriminatory ability, and its predictive ability was significantly better than using Knosp grading and postoperative immediate morning serum cortisol (PoC). The results obtained from permutation importance and LIME algorithms showed that preoperative 24-hour urine free cortisol, PoC, and age were the most important features, and showed the reliability and clinical practicability of the Adaboost model in DC prediction.

Conclusions: Machine learning-based models could serve as an effective noninvasive approach to predicting DR, and could aid in determining individual treatment and follow-up strategies for CD patients.

Keywords: Cushing’s disease; agnostic explanation; delayed remission; local interpretable model; machine learning.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • ACTH-Secreting Pituitary Adenoma / diagnosis
  • ACTH-Secreting Pituitary Adenoma / pathology
  • ACTH-Secreting Pituitary Adenoma / surgery
  • Adenoma / diagnosis
  • Adenoma / pathology
  • Adenoma / surgery
  • Adult
  • Algorithms
  • China
  • Computer Simulation
  • Female
  • Follow-Up Studies
  • Humans
  • Machine Learning*
  • Male
  • Middle Aged
  • Models, Statistical*
  • Neurosurgical Procedures
  • Pituitary ACTH Hypersecretion / diagnosis*
  • Pituitary ACTH Hypersecretion / surgery*
  • Postoperative Period
  • Prognosis
  • Remission Induction
  • Reproducibility of Results
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome
  • Young Adult