Assessing systemic 11 beta-hydroxysteroid dehydrogenase with serum cortisone/cortisol ratios in healthy subjects and patients with diabetes mellitus and chronic renal failure

11 beta -hydroxysteroid dehydrogenase (11 beta -HSD), an enzyme regulating mineralocorticoid like action of glucocorticoid, oxidizes active cortisol t o inactive cortisone, Impaired activity of this enzyme is associated with a pparent mineralocorticoid excess (AME) syndrome and is characterized by hyp ertension and hypokalemia. Recent investigations suggest the presence of hy pertensive subjects with low activity of 11 beta -HSD, The blood concentrat ion ratio of cortisone/cortisol reflects the overall conversion of cortisol to cortisone and may be an index to assess the systemic activity of 11 bet a -HSD. We evaluated the peripheral blood concentration ratio of cortisone/ cortisol as a possible marker to identify subjects with hypertension though t to represent impaired 11 beta -HSD activity. We compared this ratio in he althy subjects and patients with diabetes mellitus (DM) or chronic renal fa ilure ICRF). Peripheral blood samples were collected from 69 healthy subjec ts, 44 DM, and 36 CRF patients in the morning (9:00 to 11:00 AM). Twenty-si x DM patients (59%) and 32 CRF patients (89%) met the criteria for having h ypertension. Serum cortisol and cortisone concentrations were determined by high performance liquid chromatography (HPLC), All values for serum cortis one and cortisol levels were within the normal range. Serum cortisone/corti sol ratio in the healthy subjects was distributed with a range of 0.113 to 0.494 (median, 0.243), Compared with healthy subjects, DM and CRF patients had significantly low (P < .01) serum cortisone/cortisol levels (median, 0. 188 [range, 0.092 to 0.313] in DM and 0.088 [range, 0.031 to 0.140] in CRF) . Bimodal distribution of cortisone/cortisol, found in DM patients with hyp ertension, represented high- and low-ratio groups around the border of the ratio 0.2. Kidney function, DM duration, and complications varied between t he high- and low-ratio groups. The low ratio group (<0,2), whose 11 beta -H SD activity was considered low, had an increase in blood urea nitrogen (BUN ) levels and experienced nephropathy, neuropathy, retinopathy, and prolonge d DM duration when compared with the group with a ratio greater than 0,2, T he data suggest that the serum cortisone/cortisol ratio reflects the change in 11 beta -HSD activity and is dependent kidney function. This is a possi ble marker to evaluate glucocorticoid excess hypertension observed in DM an d CRF patients. Copyright (C) 2001 by W.B. Saunders Company.