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

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.

Automated summary

Machine learning models were developed to predict delayed remission in Cushing's disease patients who did not achieve immediate remission postoperatively. Factors such as younger age, lower body mass index, higher Knosp grade, and absence of tumor on pathological examination correlated with lower rates of delayed remission. The Adaboost model, incorporating 18 features including preoperative 24-hour urine free cortisol, postoperative morning serum cortisol, and age, showed superior predictive ability compared to traditional methods.