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  • Title: Administration of glycyrrhetinic acid: significant correlation between serum levels and the cortisol/cortisone-ratio in serum and urine.
    Author: Heilmann P, Heide J, Hundertmark S, Schöneshöfer M.
    Journal: Exp Clin Endocrinol Diabetes; 1999; 107(6):370-8. PubMed ID: 10543414.
    Abstract:
    In vitro, cortisol and aldosterone have a similar affinity to the mineralocorticoid receptor. The 11beta-hydroxysteroid dehydrogenase catalyzes the interconversion of cortisol to its inactive 11-oxo-metabolite cortisone. This interconversion is responsible for the in vivo specificity of the mineralocorticoid receptor. A defect of this enzyme leads to a pseudohyperaldosteronism with hypertension and hypokalemia, the so-called apparent mineralocorticoid excess syndrome. Glycyrrhetinic acid, a compound of licorice, also leads to pseudohyperaldosteronism by an inhibition of the 11beta-hydroxysteroid dehydrogenase. We studied the pharmacokinetics of glycyrrhetinic acid and its effect on the 11beta-hydroxysteroid dehydrogenase. Ten healthy students, aged 24 to 38 years, were included in the study. On the first day 500 mg glycyrrhetinic acid were given orally at 08.00 h. Blood and urine samples were taken prior to and 2, 4, 7, 10 and 24 hours after ingestion of glycyrrhetinic acid. We measured the serum level of cortisol, cortisone and glycyrrhetinic acid and the urinary excretion rates of cortisol, cortisone and their 20-dihydrometabolites. For determination of glycyrrhetinic acid and steroid levels we used a fully automated liquid chromatographic analyzer which allows the highly specific and simultaneous determination of steroid profiles even in the matrix of urine. Ratios of the 11-hydroxy- and 11-oxo-metabolites were calculated and correlated to the serum level of glycyrrhetinic acid. We found a significant correlation of the steroid-ratios to the serum levels of glycyrrhetinic acid. Coefficients of correlation were 0.9873, 0.7812, 0.7396 and 0.5844 between the serum level of glycyrrhetinic acid and the cortisol/cortisone-ratio in serum (p < 0.0001), the cortisol/cortisone-ratio in urine (p = 0.0279), the 20alpha-dihydrocortisol/20alpha-dihydrocortisone-ratio in urine (p = 0.0119) and the 20beta-dihydrocortisol/20beta-dihydrocortisone-ratio in urine (p = 0.0419), respectively. We conclude that the ratios of cortisol to cortisone and of the 20-dihydrometabolites of cortisol to the 20-dihydrometabolites of cortisone provide a simple noninvasive tool for monitoring the in-vivo activity of the 11beta-hydroxysteroid dehydrogenase.
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