The Physiological Disposition and Metabolic Fate of Hydrocortisone in Man

Abstract

The present report is concerned primarily with the physiological disposition and fate of hydrocortisone in man. Large doses of this steroid have been administered intravenously, and the rate of its disappearance from plasma has been determined in normal subjects and in patients with liver disease and various endocrinopathies. The following procedure is a modification of the recently published method of Silber and Porter (1):Principle-Hydrocortisone is extracted from plasma into dichloromethane. The dichloromethane extract is washed with aqueous alkali to remove a considerable amount of "blank" material. The dichloromethane is then shaken with a sulfuric acid-ethanol reagent, containing phenylhydrazine. The resulting colored product is measured in the acid phase spectrophotometrically at 410 mny. A correction for material in plasma reacting with sulfuric acid is made by treating an equal aliquot of dichloromethane extract of plasma with sulfuric acid-ethanol which contains no phenylhydrazine.

Studies on Phenolic Steroids in Human Subjects. II. The Metabolic Fate and Hepato-Biliary-Enteric Circulation of C14-Estrone and C14-Estradiol in Women1

“…Even though, in general, the importance of the biliary excretion of estrogens and their enterohepatic circulation had been accepted in the past to be true for animals, e.g., dogs, cows (6, 37), such has not been the case for human subjects. Our data demonstrate, however, that not only was more of the radioactivity of C4-estrone or C"-estradiol excreted in the bile than that seen following the injection of any other known steroid in human subjects (25,(28)(29)(30)38), but in addition more of the radioactivity appeared in the bile than in the urine of three of the bile-fistula subjects. This establishes the importance of biliary excretion in the metabolism of estrogens in women.…”

“…Since the steroids occur in the bile in conjugated form, it is possible that the free steroids present in the stool are due to the fi-glucuronidase and phenolsulfatase activities of the feces. Such activities have been demonstrated by several observers (28,41).…”

“…Similar observations were made by Beer and Gallagher (17,18). Thus, following C14-labelled cortisol (27)(28)(29), testosterone (25,26), 1 1,8-hydroxyandrostenedione (31,36) or corticosterone (30) administration, over one-third of the radioactivity is excreted in the urine in the first four hours and over 60 to 70 per cent in the first 12 hours. On the other hand, following C14-estrone or C"-estradiol administration, only 12 per cent are excreted in the first four hours and about 33 per cent after 12 hours.…”

Cortisol and dexamethasone elimination during treatment with cimetidine.

“…The terminal elimination half-life (t½) of cortisol calculated from the linear portion of the concentration time profile was similar during both treatments (placebo 1.6 h cimetidine 1.7 h) and there were no significant differences in serum cortisol concentrations between the two treatments at any time point. reported (Peterson et al, 1955). Cimetidine had no apparent effect on overall rate of cortisol elimination as estimated by serum cortisol concentrations and elimination t/.…”

Thyroid-Adrenocortical Interrelations: Failure to Demonstrate Antagonism Between Triiodo-thyronine and Hydrocortisone in Man1

“…8 Standard methods were employed for the chemical analyses (22). The urinary 17-ketosteroid determinations were made by a modification of the Zimmerman reaction (23) and the 17-hydroxysteroids by a modification (24) of the Porter-Silber method (25).…”