Clinical use of unbound plasma cortisol as calculated from total cortisol and corticosteroid-binding globulin

Abstract

A method to calculate unbound cortisol from total Cortisol (measured by competitive protein binding) and CBG (measured by radial immunodiffusion) based on the binding equilibrium has been evaluated. The calculated results ( y) correlate well with those ( x) obtained by centrifugal ultrafiltration at 37°C ( y = 1.04 x − 2.11 ng/ml; r = 0.975; n = 150). The concentration of CBG is similar in normal men (37.7 ± 3.5 (SD) μg/ml; n = 12) and women (39.5 ± 3.7 (SD) μg/ml; n = 7) and shows no diurnal variation, but marked diurnal variation is observed for total cortisol (193.7 ± 35.0 (SD) ng/ml at 08.00 h vs 43.2 ± 23.3 (SD) ng/ml at 22.00 h; n = 19) and particularly for unbound cortisol (16.5 ± 5.6 (SD) ng/ml at 08.00 h vs 2.3 ± 1.8 (SD) ng/ml at 22.00h; n = 19). The concentration of CBG (89.1 ± 11.2(SD) μg/ml) and of total cortisol (395.6 ± 103.3 (SD) ng/ml at 08.00 h; 110.3 ± 16.6 (SD) ng/ml at 22.00 h) are clearly elevated in estrogen treated women ( n = 11) but unbound cortisol levels (17.2 ± 7.7 (SD) ng/ml at 08.00 h; 2.5 ± 0.5 (SD) ng/ml at 22.00h) are similar to the control group. The concentration of CBG is significantly decreased in patients with Cushing's syndrome (33.2 ± 5.6 μg/ml; n = 17) and unbound cortisol is relatively more elevated than total cortisol in these patients. In adrenal insufficiently CBG is normal, but total and unbound cortisol are markedly decreased. There is a significant decrease of CBG in hyperthyroidism (35.7 ± 5.5 μg/ml; n = 22), in cirrhosis (32.0 ± 8.0 μg/ml; n = 14) and in renal disease and a significant increase in patients treated with antiepileptic drugs (47.5 ± 6.3 μg/ml; n = 14), but total and unbound cortisol are normal in all these conditions. We conclude that unbound cortisol can be calculated in a simple and reliable way from total cortisol and CBG and permits a better evaluation of adrenal function, particularly in patients with altered CBG concentrations.