In Vivo 11β-HSD-2 Activity: Variability, Salt-Sensitivity, and Effect of Licorice

Loss-of-function mutations or inhibition of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2) results in overstimulation of the mineralocorticoid receptor by cortisol and causes salt-sensitive hypertension. Traditionally, 11β-HSD-2 activity has been assessed by measurement of the urinary cortisol metabolite ratio (tetrahydrocortisol [THF]+5α-THF)/tetrahydrocortisone (THE). Recently, the ratio of urinary free glucocorticoids, UFF/UFE, has been suggested to be a more reliable parameter, an aspect that has not been investigated systematically. Steroid metabolites were measured repeatedly by gas chromatography–mass spectrometry in 20 healthy subjects at baseline and after 1 week each of a 30- or 180-mmol/d of sodium diet or 500 mg/d of glycyrrhetinic acid. Intraindividual coefficients of variation from 3 random urine collections for (THF+5α-THF)/THE and UFF/UFE ratios were 11±9% and 25±14% (P