SIGNIFICANCE OF THE CONCENTRATION OF NONPROTEIN-BOUND PLASMA CORTISOL IN NORMAL SUBJECTS, CUSHING'S SYNDROME, PREGNANCY, AND DURING ESTROGEN THERAPY*†

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Abstract
The concentrations of total 17-hydroxy-corticosteroid (17-OH-CS) and protein-bound 17-OH-CS were determined in plasma from various normal and abnormal subjects. The concentration of nonprotein-bound 17-OH-CS was then calculated by subtraction of the protein-bound value from the total 17-OH-CS value. Elevated plasma total 17-OH-CS concentration in Cushing''s syndrome was shown to be due entirely to an increase in the nonprotein-bound 17-OH-CS fraction. Conversely, the elevated plasma total 17-OH-CS concentration in estrogen-treated males without signs of Cushing''s syndrome was shown to be due entirely to an increase in the protein-bound 17-OH-CS. In women in the third trimester of pregnancy (with signs of mild adrenocortical hyperfunction) the levels of both protein-bound and nonprotein-bound plasma 17-OH-CS were increased. It is suggested that the nonprotein-bound plasma 17-OH-CS fraction is the immediately active form of cortisol. It probably has high activity because it is able to diffuse readily across capillaries and cell membranes.