Assessing systemic 11beta-hydroxysteroid dehydrogenase with serum cortisone/cortisol ratios in healthy subjects and patients with diabetes mellitus and chronic renal failure.
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.
Homma
M
M
Department of Pharmaceutical Sciences, Institute of Clinical Medicine, University of Tsukuba, Amakubo, Tsukuba, Ibaraki, Japan.
Tanaka
A
A
Hino
K
K
Takamura
H
H
Hirano
T
T
Oka
K
K
Kanazawa
M
M
Miwa
T
T
Notoya
Y
Y
Niitsuma
T
T
Hayashi
T
T
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000328:Adult; D015992:Body Mass Index; D003348:Cortisone / Q000097:blood*; D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D006973:Hypertension / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism*; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008297:Male
D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003348:Cortisone; D006854:Hydrocortisone