Abstract
Plasma unbound cortisol concentration is an accurate measure of its physiological activity. As unbound cortisol is excreted from plasma into saliva, it may be possible to non-invasively predict plasma unbound cortisol levels using salivary cortisol levels. However, part of the salivary cortisol is converted to cortisone, which can affect such predictions. Therefore, correlation between salivary cortisol and plasma unbound cortisol was analyzed in healthy subjects (n=9) and the effect of cortisol-to-cortisone conversion on this correlation was investigated. The correlation equation between salivary cortisol concentration (range, 0.26–3.22 ng/mL) and plasma unbound cortisol concentration (range, 0.31–2.74 ng/mL) for all subjects was determined to be y=0.5311x+0.5117 (r=0.51); however, it showed low correlation. Then, as individual differences in the slope of the correlation equation ranged from 0.62 to 2.62, we classified subjects into two groups based on a mean slope value of 1.10 and re-evaluated the correlation. The resulting equations yielded better correlations (y=2.0416x+0.0279, r=0.65, for two subjects and y=0.7417x+0.1195, r=0.77, for seven subjects), and the observed variation in slope was attributed to individual differences in salivary 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) activity. Importantly, mean absolute percentage error in predicting plasma cortisol using salivary cortisol levels using the two correlation equations was 0.6%. Thus, these results suggest that deriving and classifying salivary cortisone/cortisol ratio, along with relevant correlation equations, can be used to non-invasively predict plasma unbound cortisol concentration.
