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The metabolism of [4-14C]cortisol in a patient with Cushing's syndrome has been studied by the isolation, identification and measurement of the specific radioactivities of the major metabolites.The results show that the metabolism of cortisol was not abnormal in the aspects studied. The biological half-lives of cortisol and of the tetrahydrocorticosteroid metabolites were found to be normal. Data obtained on excretion rates of metabolites indicated that the metabolic pathways of cortisol were normal. There was no evidence for an increased conversion of cortisol to 6ß-hydroxycortisol when the excretion of the latter was expressed as a fraction of the cortisol production.The overall pattern was one of an abnormally high secretion of cortisol by the adrenals, resulting in a proportionally high excretion of tetrahydrocortisone, tetrahydrocortisols, cortolones, cortols, 11-oxygenated 17-oxosteroids, 6ß-hydroxycortisol, cortisone and cortisol. Apart from an increased ratio of 11ß-hydroxy-metabolites to 11-oxo-metabolites, each metabolite, expressed as a fraction of the cortisol secreted, was excreted in a normal proportion.Hence, in spite of the grossly elevated cortisol secretion rate, the major pathways available for cortisol metabolism were not overloaded and there was no evidence of increased metabolism via minor pathways.Evidence for an increased secretion of corticosterone by the adrenals was obtained by the isolation of abnormal amounts of tetrahydrocorticosterone.

The binding of plasma cortisol to transcortin at 37° cwas studied in normal men and in non-pregnant and pregnant women. The mean concentrations of transcortin were 8, 11·5 and 14 × 10−7moles/l. and the percentages of the binding sites occupied by cortisol were 45, 24 and 40%, respectively. The mean values of the equilibrium constants were 2·9, 1·8 and 4·6 × 107l./mole, suggesting that there might be a qualitative difference in transcortin from the three groups. The mean concentration of diffusible cortisol was 1·12 μg./100 ml. in men and 0·65 μg./100 ml. in non-pregnant and pregnant women.The significance of these findings is discussed.