Impaired conversion of cortisol to cortisone in chronic renal insufficiency--a cause of hypertension or an epiphenomenon?

To study the possible impairment of 11 beta-hydroxysteroid-dehydrogenase in patients with chronic renal insufficiency, urinary excretion rates of the four main glucocorticoid-metabolites, tetrahydrocortisol, tetrahydrocortisone, allotetrahydrocortisol and allotetrahydrocortisone were determined by capillary gas chromatography in 22 patients with chronic renal insufficiency with (N = 15) and without (N = 7) hypertension, but without hemodialysis treatment. Whereas the sum of all 41 steroid metabolites determined by capillary gas chromatography was reduced (p less than 0.001) in patients with chronic renal insufficiency as compared with 22 healthy individuals, the relative contribution of the four glucocorticoid metabolites to total steroid excretion was similar in patients with renal insufficiency (22 +/- 12%) and in healthy subjects (20 +/- 5%). However, the excreted amount of tetrahydrocortisol exceeded that of tetrahydrocortisone in all but 3 (normotensive) patients with chronic renal insufficiency, but only in one healthy subject resulting, in patients with chronic renal insufficiency, in a ratio of tetrahydrocortisone vs tetrahydrocortisone of 0.7 +/- 0.4 (hypertensive patients 0.5 +/- 0.2; normotensive patients 1.1 +/- 0.4; controls 1.9 +/- 0.9, p less than 0.001 vs patients with chronic renal insufficiency). This ratio of tetrahydrocortisone/tetrahydrocortisol showed a correlation with serum concentrations of creatinine (p less than 0.001). These results provide indirect proof of an impaired conversion of cortisol to cortisone in moderate renal insufficiency and may suggest a relationship with the hypertension frequently seen in this group of patients.