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RICHARD P. DOE, HORACE H. ZINNEMAN, EDMUND B. FLINK, ROBERT A. ULSTROM, RUTH ENGST, MARY LEWIS, JANET JOHNSON, SIGNIFICANCE OF THE CONCENTRATION OF NONPROTEIN-BOUND PLASMA CORTISOL IN NORMAL SUBJECTS, CUSHING'S SYNDROME, PREGNANCY, AND DURING ESTROGEN THERAPY, The Journal of Clinical Endocrinology & Metabolism, Volume 20, Issue 11, 1 November 1960, Pages 1484–1492, https://doi.org/10.1210/jcem-20-11-1484
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The concentrations of total 17-hydroxycorticosteroid (17-OH-CS) and protein- bound 17-OHCS 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.
