Studies on Cortisol Substitution Therapy in Patients with Adrenal Insufficiency

Abstract

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.

Quality of Life in Patients with Addison's Disease:

“…The lowest ratios of contentment and well-being were seen with mode III (placebo in the morning and 30 mg HC in the evening) demonstrating the most severe disturbance of psychological performance through this exceptionally non-physiological cortisol medication. The results confirm the suggestion that the extent of the hypothalamic-hypophyseal-adrenal dysregulation correlate closely to the psychological performance in Addison patients (Nickelsen et al, 1983;Groves et al, 1988). Since we have not repeated self-rating during different times of a day, we cannot exclude circadian variations of well-being and psychological performance in order to actual cortisol levels in this study (Groves et al, 1988).…”

“…In fact, these patients often complain on a reduction of general well-being, mood, and physical activity during conventional maintenance therapy (Groves et al, 1988;Nikkelsen et al, 1983). Although the influence of different modes of cortisol replacement on these changes have been mentioned by several authors (Allolio et al, 1978;Loriaux, 1990;Nickelsen et al, 1983) and hormonal studies were recommended as a diagnostic aid to reach contentment in Addison patients (Kley and Krüskemper, 1978), this relation has rarely been elucidated by sufficient techniques previously.…”

Inadequacies of glucocorticoid replacement and improvements by physiological circadian therapy

“…Originally, cortisol deficiency was more commonly treated with cortisone acetate (25 mg in the morning and 12.5 mg in the evening), but this drug is now less frequently used and needs to be converted to HC by the enzyme 11b hydroxysteroid dehydrogenase (11bHSD1) type 1 to become active. On the other hand, when compared with HC, it shows a lower serum cortisol peak and possible delayed clearance of cortisol (63,64) properties that may be advantageous.…”

Impaired subjective health status in chronic adrenal insufficiency: impact of different glucocorticoid replacement regimens

“…In PAI, this is also associated with intermittent excess of circulating ACTH. Cortisone acetate (CA), used in the study by Lovas et al (3) in Norway, seems to have a lower serum cortisol peak and a delayed decline of cortisol levels (10,11). However, cortisol generation may be occasionally affected by an impaired 11b-hydroxysteroid reductase activity (12).…”