How useful is urinary-free cortisol in the clinic?

Measurement of 24-h urine-free cortisol is frequently employed as a first-line screening and disease-monitoring test in Cushing's syndrome (CS). The quest for ‘cortisol specificity’ has seen the emergence of mass spectrometry (MS) based assays, particularly liquid chromatography/tandem mass spectrometry. In contrast to traditional immunoassays, liquid chromatography/tandem mass spectrometry ‘free cortisol’ measurement is less susceptible to ‘interference’ from cortisol precursors and metabolites. However, detection of these conjugates is important in mild CS and therefore, missed by MS if cortisol alone is measured. MS assays nevertheless are capable of measuring broad steroid profiles, including the potential to distinguish benign from malignant adrenal-based CS and detection of exogenous glucocorticoids. Until this is routine practice, we recommend against abandoning immunoassays measurement of urine-free cortisol.