Clinical Studies on the Secretion and Metabolism of Cortisol and Aldosterone

Abstract

The tracer doses of tritiated aldosterone and tritiated or carbon-14 cortisol were injected intravenously in 10 cases with liver cirrhosis, 2 cases with acute hepatitis, a case with chronic hepatitis, 4 cases with hyperthyroidism, 3 cases with hypothyroidism and a case with cancer of the prostate. Daily secretion rate, mean plasma concentration, speed of metabolism, metabolic clearance rate, volume of distribution space and miscible pool of aldosterone and cortisol were calculated in these patients using two compartmental models of human body, discribed by Tait et al. Urinary metabolites of these radioactive steroid hormones were also estimated.1) In all patients with liver cirrhosis, the delayed metabolism of cortisol and aldosterone was shown. Increased daily secretion rate, mean plasma concentration and miscible pool were found in most but not all patients with liver cirrhosis. The secretion rate of cortisol decreased in all cases with lirver cirrhosis. There were some changes in the metabolism of aldosterone and cortisol in patients with liver cirrhosis compared with normal subjects. Increased urinary excretion of free fraction of cortisol and aldosterone, and 3-oxo-conjugate of aldosterone and elevated tetrahydrocortisol/ tetrahydrocortisone ratio were found, while glucuronide fractions of these hormones in urine were decreased in patients with liver cirrhosis. These results suggest that there is decreased conversion to metabolites conjugated with grucuronic acid and reduced reaction of 11, β-hydroxylation in patients with liver cirrhosis.2) In acute hepatitis, slightly delayed metabolism of cortisol and aldosterone was observed, but in chronic hepatitis, no significant changes in metabolism of these hormones compared with that in normal control, were obtained.3) In hyperthyroidism, the speed of metabolism of cortisol was higher than normal controls. However, these values for aldosterone were slightly elevated. Urinary free fraction of cortisol was reduced, but metabolites conjugated with glucuronic acid were increased. The ratio of tetrahydrocortisol/tetrahydrocortisone in urine was decreased.4) In hypothyroidism, the daily secretion rate of cortisol and aldosterone was decreased, but mean plasma concentration of these hormones was within normal range or slightly elevated, while metabolic clearance rate or speed of metabolism of these hormones was markedly decreased. Urinary free faction of these hormones was increased. Tetrahydrocortisol/tetrahydrocortisone ratio in urine was elevated. These results suggest that thyroid hormone accelarates the metabolism of these steroid hormones, and that it may play some role in the activation of 11 β-hydroxysteroid dehydrogenase in liver.5) On the administration of estrogens, delayed metabolism of cortisol and aldosterone was observed. Mean plasma concentration of these steroid hormones was markedly elevated.