11beta-hydroxysteroid dehydrogenase (11beta-HSD), an
enzyme regulating
mineralocorticoid like action of
glucocorticoid, oxidizes active
cortisol to inactive
cortisone. Impaired activity of this
enzyme is associated with apparent
mineralocorticoid excess (
AME) syndrome and is characterized by
hypertension and
hypokalemia. Recent investigations suggest the presence of hypertensive subjects with low activity of 11beta-HSD. The blood concentration ratio of
cortisone/
cortisol reflects the overall conversion of
cortisol to
cortisone and may be an index to assess the systemic activity of 11beta-HSD. We evaluated the peripheral blood concentration ratio of
cortisone/
cortisol as a possible marker to identify subjects with
hypertension thought to represent impaired 11beta-HSD activity. We compared this ratio in healthy subjects and patients with
diabetes mellitus (DM) or
chronic renal failure (CRF). Peripheral blood samples were collected from 69 healthy subjects, 44 DM, and 36 CRF patients in the morning (9:00 to 11:00 AM). Twenty-six DM patients (59%) and 32 CRF patients (89%) met the criteria for having
hypertension. Serum
cortisol and
cortisone concentrations were determined by high performance liquid chromatography (HPLC). All values for serum
cortisone and
cortisol levels were within the normal range. Serum
cortisone/
cortisol 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
hypertension, represented high- and low-ratio groups around the border of the ratio 0.2. Kidney function, DM duration, and complications varied between the high- and low-ratio groups. The low ratio group (<0.2), whose 11beta-HSD activity was considered low, had an increase in blood
urea nitrogen (BUN) levels and experienced nephropathy, neuropathy, retinopathy, and prolonged DM duration when compared with the group with a ratio greater than 0.2. The data suggest that the serum
cortisone/
cortisol ratio reflects the change in 11beta-HSD activity and is dependent kidney function. This is a possible marker to evaluate
glucocorticoid excess
hypertension observed in DM and CRF patients.