Endocrine Abstracts

Background: When evaluating a patient for central adrenal insufficiency (CAI), there is a wide range of morning cortisol values for which no final conclusion on hypothalamus-pituitary-adrenal (HPA) axis function can be drawn; in these cases, a stimulation test is required. Aim of this study was to develop an integrated model for the prediction of CAI when morning cortisol is in the grey zone, here defined as 40.0-160.0 μg/l.

Methods: Overall, 119 patients with history of sellar tumour which underwent insulin tolerance test (ITT) for the evaluation of HPA axis were enrolled; a peak cortisol value ≥ 180.0 μg/l at ITT was adopted for the definition of CAI. Supervised regression techniques were used for model development. Model calibration was evaluated by the Hosmer-Lemeshow test. A ten-fold cross-validation algorithm was adopted for internal validation.

Results: After a stepwise backward selection, the variables retaining a statistically significant association with the outcome were morning cortisol values, the presence of ≥ 3 other pituitary deficits, and male sex. Based on these predictors, a multivariable predictive model was developed, and showed a significantly better diagnostic performance in the prediction of CAI than morning cortisol alone (AUC 0.811 vs 0.699, P=0.003). The Hosmer-Lemeshow test did not reveal any significant miscalibration (P=0.54). At ten-fold cross-validation, the final estimation of the model performance on unseen data was equal to 0.769, thus reassuring about a small overfitting effect. In order to simplify the use of the model in clinical practice, a novel predictive score (CAI-score) is proposed, on a 5.5-point scale, by considering morning cortisol (0 points if 130.1-160.0 μg/l, 1 point if 100.1-130.0 μg/l, 1.5 points if 70.1-100.0 μg/l, 2.5 points if 40.0-70.0 μg/l), other pituitary deficits (2 points if ≥3 deficits), and sex (1 point if male). A diagnostic algorithm integrating CAI-score and ITT is finally presented, with an overall accuracy of 99.2%, and the possibility to avoid the execution of a stimulation test in 25.2% of patients.

Conclusion: This was the first study that formally proposed and internally validated a multivariable predictive score for the diagnosis of CAI when morning cortisol is in the grey zone. This score might be helpful to reduce the number of patients who need a stimulation test for the assessment of HPA axis function.