A New Clinical Model to Estimate the Pre-Test Probability of Cushing's Syndrome: The Cushing Score

Background Hypercortisolism accounts for relevant morbidity and mortality and is often a diagnostic challenge for clinicians. A prompt diagnosis is necessary to treat Cushing's syndrome as early as possible. Objective The aim of this study was to develop and validate a clinical model for the estimation of pre-test probability of hypercortisolism in an at-risk population. Design We conducted a retrospective multicenter case-control study, involving five Italian referral centers for Endocrinology (Turin, Messina, Naples, Padua and Rome). One hundred and fifty patients affected by Cushing's syndrome and 300 patients in which hypercortisolism was excluded were enrolled. All patients were evaluated, according to current guidelines, for the suspicion of hypercortisolism. Results The Cushing score was built by multivariable logistic regression, considering all main features associated with a clinical suspicion of hypercortisolism as possible predictors. A stepwise backward selection algorithm was used (final model AUC=0.873), then an internal validation was performed through ten-fold cross-validation. Final estimation of the model performance showed an average AUC=0.841, thus reassuring about a small overfitting effect. The retrieved score was structured on a 17.5-point scale: low-risk class (score value: <= 5.5, probability of disease=0.8%); intermediate-low-risk class (score value: 6-8.5, probability of disease=2.7%); intermediate-high-risk class (score value: 9-11.5, probability of disease=18.5%) and finally, high-risk class (score value: >= 12, probability of disease=72.5%). Conclusions We developed and internally validated a simple tool to determine pre-test probability of hypercortisolism, the Cushing score, that showed a remarkable predictive power for the discrimination between subjects with and without a final diagnosis of Cushing's syndrome.

Automated summary

A clinical model, the Cushing score, was developed and validated to estimate the pre-test probability of hypercortisolism in high-risk population, showing remarkable predictive power for discriminating between patients with and without Cushing's syndrome.