Effect of glucocorticoid excess on the cortisol/cortisone ratio.
OBJECTIVE
The conversion of cortisol, which binds avidly to the mineralocorticoid receptor, to cortisone, which no longer has mineralocorticoid function, is predominantly catalyzed by the 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD 2). It was the objective of the present study to examine the impact of different forms of glucocorticoid excess on the cortisol/cortisone ratio and to differentiate their role in the genesis of hypertension.


METHODS
Plasma cortisol and cortisone levels were determined in 12 adults with Cushing's disease, 12 adults with hypercortisolism due to an adrenal tumor, and 20 healthy volunteers before and after an intravenous ACTH test, using specific radioimmunoassays after automated Sephadex LH 20 chromatography.


RESULTS
The cortisol/cortisone ratios were significantly higher in patients with Cushing's disease (13.9 +/- 1.1), adrenal tumors (11.5 +/- 2.3), and in healthy volunteers after ACTH stimulation (14.1 +/- 2.0) than in untreated controls (6.0 +/- 0.5) (P < 0.001, P < 0.05, and P < 0.001, respectively). Similar differences were seen for cortisol plasma concentrations, whereas cortisone concentrations did not differ among the groups.


CONCLUSIONS
Our data suggest that the excessive mineralocorticoid effects in patients with hypercortisolism are inflicted by elevated cortisol/cortisone ratios possibly due to an insufficient conversion of cortisol to cortisone by 11beta-HSD 2. This may provide a possible explanation for the occurrence of hypertension. This effect seems to be independent of the role of ACTH in the mechanism of hypercortisolism.
Dötsch
J
J
Department of Pediatrics, University of Erlangen-Nürnberg, Loschgestr. 15, D-91054 Erlangen, Germany. JoergWDoetsch@yahoo.com
Dörr
H G
HG
Stalla
G K
GK
Sippell
W G
WG
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000310:Adrenal Gland Neoplasms / Q000150:complications; D000308:Adrenocortical Hyperfunction / Q000097:blood* / Q000209:etiology; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage* / Q000097:blood; D000328:Adult; D000368:Aged; D003348:Cortisone / Q000097:blood*; D003480:Cushing Syndrome / Q000097:blood / Q000150:complications; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000819:agonists* / Q000097:blood*; D006913:Hydroxysteroid Dehydrogenases / Q000187:drug effects* / Q000378:metabolism; D006973:Hypertension / Q000209:etiology; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D008901:Mineralocorticoids / Q000097:blood; D013268:Stimulation, Chemical
D008901:Mineralocorticoids; D000324:Adrenocorticotropic Hormone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003348:Cortisone; D006854:Hydrocortisone