Metabolism of Free and Conjugated 17-Hydroxycorticosteroids in Subjects With Thyroid Disease*

Levels of free and conjugated 17-hydroxycorticosteroids (17-OHCS) in plasma were measured after intravenous infusions of cortisol, tetrahydrocortisone (Tetra E) and adrenocorticotropic hormone (ACTH) in subjects wi h hyperthyroidism and hypothyroidism. After administration of cortisol to hyperthyroid patients, the levels of free 17-OHCS decayed more rapidly than normal, while those of conjugated 17-OHCS rose faster and to higher values than in normal subjects. The opposite occurred in hypothyroid patients. Conjugation of administered Tetra E was increased in hyperthyroid patients but was normal in those with hypothyroidism. Plasma concentrations of free 17-OHCS were influenced more by the rate of removal from plasma than by the adrenal response to ACTH in both types of subjects. Accordingly the level of free 17-OHCS after ACTH was a misleading index of adrenocortical function, as the rise was greatest in hypothyroid patients and least in those with hyperthyroidism. The level of conjugated 17-OHCS after infusion of ACTH was highest in hyperthyroid patients and lowest in hypothyroid patients; it reflected accurately the state of adrenocortical activity. The amount of unstimulated excretion of 17-OHCS in the urine was in keeping with this observation, the total output varying directly with basal metabolic rate. In patients restudied after appropriate therapy, the metabolism of, 17-OHCS returned towards normal. In hyperthyroidism the removal of cortisol from plasma and the formation of conjugated 17-OHCS occur more rapidly than normal, the reverse being true in hypothyroidism. Since conjugation of Tetra E appears to be normal in hypothyroidism, the apparent failure of conjugation after administration of cortisol probably results from decreased reduction of cortisol to substrates needed for conjugation. For proper assessment of adrenocortical function it is necessary to determine the rate of removal of 17-OHCS from plasma, as well as the response to ACTH, and the urinary excretion of these steroids. Results of such an analysis suggest that adrenocortical activity varies directly with basal metabolic rate.