ADDITIONAL VALUE OF MEASUREMENT OF URINARY CORTISONE AND UNCONJUGATEDCORTISOL METABOLITES IN ASSESSING THE ACTIVITY OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE IN-VIVO

OBJECTIVE it has been shown recently that 11 beta-hydroxysteroid dehyd rogenase (11 beta-HSD) is expressed as at least 2 isozymes, In the liv er, 11 beta-HSD1 converts cortisone to cortisol; in the kidney, 11 bet a-HSD2 converts cortisol to cortisone, Conventional assessment of 11 b eta-HSD activity in vivo has relied on gas chromatographic measurement of the ratios of conjugated cortisol and cortisone metabolites. Howev er, these do not permit distinction between the tissue-specific activi ties of the enzymes and do not reflect all forms of 11 beta-HSD defici ency, In this report, we have assessed the usefulness of measuring unc onjugated cortisol metabolites and free cortisol and cortisone in urin e as indices of renal 11 beta-HSD activity in man. DESIGN Six healthy male subjects established in sodium balance were given either glycyrrh etinic acid (170 mg t.d.s., to inhibit 11 beta-HSD2), carbenoxolone (1 00 mg t.d.s., to inhibit both 11 beta-HSD1 and 11 beta-HSD2) or both i nhibitors in combination, MEASUREMENTS Urinary electrolytes were measu red and the concentrations of total and unconjugated urinary cortisol and its metabolites were determined by gas chromatography mass spectro metry, RESULTS Glycyrrhetinic acid and carbenoxolone inhibited renal 1 1 beta-HSD2 to a similar degree, as judged by similar sodium retention . As previously reported, conventional measurement of ratios of total cortisol to cortisone metabolites were influenced to a greater extent by glycyrrhetinic acid (100-200% increase in ratio from baseline) than by carbenoxolone (<30% increase), However, the effect of carbenoxolon e was readily detected by measurement of urinary unconjugated cortisol /cortisone (130-480% increase of ratio from baseline) and also by meas urement of ratios of unconjugated cortisol metabolites (60-130% increa se). CONCLUSIONS Measurement of free cortisol and cortisone in urine p rovides the most sensitive index of renal 11 beta-HSD activity, Measur ement of total and conjugated urinary steroids is insensitive in circu mstances where 11 beta-HSD activity in liver or elsewhere may be abnor mal.