Cortisol: Analytical and clinical determinants

Cortisol, the main human glucocorticoid, is synthesized from cholesterol in the adrenal cortex and predominantly metabolized by the liver. Interpretation of quantitative results from the analysis of serum, urine and saliva is complicated by variation in circadian rhythm, response to stress as well as the presence of protein-bound and free forms. Interestingly, cortisol is the only hormone routinely measured in serum, urine, and saliva. Preanalytical and analytical challenges arise in each matrix and are further compounded by the use of various stimulation and suppression tests commonly employed in clinical practice. Although not yet included in clinical guidelines, measurement of cortisol in hair may be of interest in specific situations. Immunoassays are the most widely used methods in clinical laboratories to measure cortisol, but they are susceptible to interference from synthetic and endogenous steroids, generally producing a variable overestimation of true cortisol results, especially in urine. Analysis by mass spectrometry provides higher specificity and allows simultaneous measurement of multiple steroids including synthetic steroids, thus reducing diagnostic uncertainty. An integrated review of cortisol in various disease states is also addressed.