Measurements and signification of unbound cortisol in plasma

It is generally accepted that transcortin-bound cortisol in plasma has no direct hormonal activity. For that reason unbound cortisol, rather than total cortisol will reflect hormonal impregnation. In this communication we present a method to calculate unbound cortisol from total cortisol and from the concentration of transcortin based on the binding equilibrium. The results of this technique correlate very well with those obtained by centrifugal ultrafiltration at 370C (R=0.988, y=0.986+0.862xX; n=20) showing the validity of this technique. The diurnal variation of transcortin and of total or unbound cortisol was studied in normal adult volunteers. No diurnal variation was observed for transcortin and the concentration of this protein was identical in normal men [38.3+-3.1(SD)mg/l, n=17] and women (38.9+-4.6 mg/l; n=5) but markedly higher (89.9+-14.6 mg/l, n=9) in estrogen-treated women. As expected both total and unbound cortisol showed marked diurnal variation with relatively high levels at 8 AM (total cortisol 23.5+-2.7 μg% in men and 25.8+-6.1 μg% in women); unbound cortisol 2.3+-0.5 μg% in men; 3.0+-1.6 μg% in women) and low levels at 10 PM (total cortisol 4.9+-3.3 μg% in men, 5.7+-2.8 μg% in women; unbound cortisol 0.2+-0.1 μg% in men; 0.3+-0.1μg% in women). In estrogen-treated women the levels of total cortisol were about twice as high at all timepoints, but the unbound cortisol concentrations were similar. These results indicate that the unbound cortisol is not affected by the changed concentration of transcortin. In patients with Cushing's disease, on the other hand, the unbound cortisol is relatively more elevated than the total cortisol due to a high degree of saturation of this protein, which is often present at relatively low concentrations