The Effect of Intravenous Cortisol Injections on the Plasma Cortisol Concentration in Man 1

Abstract

Previous workers have shown (1-7) that 17-hydroxycorticosteroids disappear rapidly from the plasma after cortisol (hydrocortisone) is injected intravenously. The disappearance rates have not, however, been studied in detail nor have analytical methods been used which would distinguish cortisol from its reduced derivatives. In the present experiments disappearance curves of cortisol have been determined, both after sudden massive injections, and during slow infusions at rates which permitted the establishment of equilibrium at physiological plasma cortisol concentrations. Steroid determinations have been performed by methods which separate cortisol from all other steroids known to be present in human plasma. MATERIALS AND METHODSAll subjects were healthy male medical students between the ages of 21 and 25. years, without evidence of serious disease or history of hepatic, renal or endocrinological abnormality. Studies were started between 8:30 and 9:30 a.m. The subjects were ambulatory but otherwise inactive. They were on normal diets throughout the experiment and all understood the nature of the procedure. Five subjects were used in each part and those who participated in Part I were not used in Part II.Heparinized blood samples were centrifuged immediately upon withdrawal and except in a few cases were extracted the same day. On occasion it was necessary to freeze the plasma for a few days prior to extraction. The plasma samples were analyzed by the method of Bondy, Abelson, Scheuer, Tseu, and Upton (8, 9), a brief description of which follows.Appropriate duplicate quantities of plasma were extracted with chloroform and the extracts chromatographed in the Bush toluene-75 per cent methanol paper chromatography system. Cortisol spots were eluted with ethyl alcohol and the quantity of steroid measured by potassium butoxide fluorometry (8). cortisol-4-C"4 were added to the original plasma sample and the radioactive recovery used to correct for losses during the procedure. The calculated standard deviation between duplicate samples with this method is +7 per cent, and recovery of added cortisol is 100 + 14 per cent. EXPERIMENTAL PROCEDUREPart I: A control blood specimen was drawn and then 100 mg. of cortisol (Upjohn) in 150 ml. of 6.7 per cent alcohol and 5 per cent glucose in water were injected over a 5-minute period through the same needle. Blood samples were taken at 15, 60, 150, 300, and 420 minutes from a vein in the opposite arm. In two subjects samples were taken every 15 minutes for the first hour and every 20 minutes for the second hour. The total amount of blood drawn was 320 ml.Part II: After an initial blood sample had been drawn, an infusion of cortisol in 500 ml. of 5 per cent glucose (Merck) was injected intravenously through a constant infusion pump at approximately 300 ,ug. per minute. Thereafter blood was withdrawn from the opposite arm at 60, 165, 180, 300, and 480 minutes. After withdrawal of the 180-minute sample the infusion was stopped and the solution run through the pump and needle into a 10...

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