Serum cortisol/cortisone ratio after Synacthen stimulation.
OBJECTIVE
11beta-Hydroxysteroid dehydrogenase (11beta-HSD) enzymes interconvert active cortisol and inactive cortisone. There is growing evidence that local tissue concentrations of cortisol are generally modulated by site specific different 11beta-HSD actions. While 11beta-HSD type 2 unidirectionally inactivates cortisol, type 1 isoform acts bidirectionally. 11beta-HSD type 1 is mainly localized in the liver and may thus restore circulating biologically inactive cortisone to active cortisol thereby modulating systemic glucocorticoid action; such a mechanism might be of importance in stressful situations. To study this hypothesis we investigated the influence of exogenous ACTH on serum cortisol/cortisone ratio.


METHODS
Paired serum samples that were submitted for routine analysis of cortisol before and 1 h after stimulation with 250 microg ACTH (1-24) (Synacthen) were collected prospectively if the routine tests indicated normal adrenal function; 40 patients were included in the study, 29 patients were female, 11 male, median age was 31 yr (range 14-70). Serum cortisol and cortisone were determined using LC-ESI/MS/MS with an online sample extraction system and tri-deuterated cortisol as the internal standard.


RESULTS
While mean serum cortisol increased by 109% (mean basal concentration 373 nmol/L (SD 151 nmol/L), stimulated 781 nmol/L (SD 194 nmol/L)), mean serum cortisone significantly decreased after ACTH administration by 31% (p < 0.001, paired t-test for differences). Mean serum cortisone was 70 nmol/L (SD 16 nmol/L) before and 48 nmol (SD 16 nmol/L) after ACTH administration; decrease in serum cortisone was observed in 34 (85%) of the patients. The ratio of serum cortisol/cortisone increased in all subjects (mean 5.4 (SD 1.9) before ACTH, and 16.2 (SD 6.2) after ACTH; p < 0.001).


CONCLUSIONS
The data of our observational study suggest a modulation of peripheral metabolism of cortisol by ACTH with a stimulation of systemic 11beta-HSD type 1 activity, leading to restoration of inactive cortisone to biologically active cortisol.
Vogeser
M
M
Institute of Clinical Chemistry, Ludwig-Maximilians-Universität Munich, Klinikum Grosshadern, 81366, Munich, Germany. mvogeser@klch.med.uni-muenchen.de
Zachoval
R
R
Jacob
K
K
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D003348:Cortisone / Q000097:blood*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D021241:Spectrometry, Mass, Electrospray Ionization; D013268:Stimulation, Chemical; D013997:Time Factors
D007527:Isoenzymes; D000324:Adrenocorticotropic Hormone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003348:Cortisone; D006854:Hydrocortisone