Current challenges in Cushing's syndrome testing: blood, saliva, urine, or hair?

Endogenous Cushing's syndrome is one of the most difficult diagnoses in endocrinology. It is mainly based on biochemical tests that assess qualitative and quantitative alterations in cortisol production. Whether performed on blood, saliva, urine, or hair, the biochemical tests currently available have limited diagnostic specificity and sensitivity. Their performance varies depending on the individual characteristics of the patient, the stage of the disease, and the laboratory techniques used to determine cortisol levels. Knowledge of these factors will help physicians choose the most appropriate diagnostic test for each individual.

Relevant studies and meta-analyses have clarified the actual performance of various biochemical tests in a real-world setting. In addition, the diagnostic arsenal for Cushing's syndrome has been expanded with new tools, such as hair cortisol and cortisone assays, new methods for measuring cortisol in urine or saliva, and new approaches such as steroid metabolomics or multiomics techniques.

This review is a critical reappraisal of the merits and drawbacks of the various "old" and new biochemical tools. Its purpose is to provide the physician with practical advice on the use of biochemical tests at various stages of Cushing's syndrome in order to improve diagnostic accuracy.