Altered equilibrium between cortisol and cortisone in plasma in thyroid dysfunction and inflammatory diseases

The radioactivities of cortisol and cortisone in plasma were determined following simultaneous injection of ¹⁴C-cortisol and ³H-cortisone. The plasma concentrations of ¹⁴C-cortisol and ³H-cortisone decreased as a first-order function of time after an initial rapid drop, while there was a prompt appearance of ¹⁴C-cortisone and ³H-cortisol in plasma, which also decreased as a first-order function. The biologic half-lives of these four isotopic steroids were essentially identical. The ratio of ¹⁴C-cortisone to ¹⁴C-cortisol and that of ³H-cortisone to ³H-cortisol in plasma were constant after 60 min following injection and were identical, which suggested that cortisol and cortisone in plasma were at dynamic equilibrium. This ratio was 0.36 ± 0.01 (SE) in normals; it was decreased in patients with hypothyroidism (0.21 ± 0.03) and inflammatory diseases (0.18 ± 0.01) and was variable in hyperthyroid patients (0.42 ± 0.11). The ratio of the metabolic clearance rate of cortisone to that of cortisol was significantly increased in hypothyroid patients and in patients with inflammatory diseases, while urinary 11-ketonic metabolites of cortisol are known to decrease relative to its 11-hydroxy metabolites in these patients. These data and the decreased cortisone-to-cortisol ratio at equilibrium were consistent with the altered equilibrium between cortisol and cortisone, favoring cortisol, in these patients. It was suggested that the altered equilibrium between these steroids may be an important factor in determining the effectiveness of secreted or exogenously administered cortisol and the plasma concentration of cortisone in several disorders.