Studies on cortisol substitution therapy in patients with adrenal insufficiency

To eight patients with Addison's disease 25 mg of cortisone acetate or cortisol, respectively, was given orally. Thereafter blood samples were taken and analysed for total cortisol, "free" (not protein bound) cortisol and ACTH. Furthermore, urine cortisol excretion and the cortisol binding capacity of the plasma were determined. We found that after the substitution therapy the increase of the plasma cortisol was variable and reached its maximum after 45 to 240 minutes. However, if the resorption time was subtracted the individual differences were less pronounced and plasma cortisol levels above 8 micrograms/dl could be maintained for about six hours. When cortisol was taken instead of cortisone acetate the increase of the plasma cortisol was steeper, decreasing then more rapidly. Plasma "free" cortisol ranged from 2.75 to 6.19% in relation to total cortisol and closely paralleled the level of total cortisol in each patient during the course of the experiment. The excretion of unconjugated cortisol in urine amounted to 56.5 +/- 26 micrograms (SE) and was better correlated to the concentration of "free" cortisol than to total plasma cortisol. The behaviour of plasma ACTH levels was variable. Great fluctuations with high morning levels and good suppression was observed in patients having their substitution tablet only in one single morning dose. From these biochemical data recommendations for the substitution therapy in patients with adrenal insufficiency were given.