Endogenous corticosteroid biosynthesis in subjects after bilateral adrenalectomy

Freel, E.M., Bernhardt, M., Ingram, R., Wallace, A.M., Fraser, R., Davies, E. and Connell, J.M.C. (2007) Endogenous corticosteroid biosynthesis in subjects after bilateral adrenalectomy. Clinical Endocrinology, 66(5), pp. 659-665. (doi:10.1111/j.1365-2265.2007.02791.x)

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Publisher's URL: http://dx.doi.org/10.1111/j.1365-2265.2007.02791.x

Abstract

<b>Objective:</b>  Corticosteroids can be synthesized in extra-adrenal tissues but the contribution of this to circulating levels in humans is not known. Previous in vitro studies suggest that the ‘hybrid’ corticosteroid 18-oxocortisol (18-oxoF) is produced from cortisol by aldosterone synthase. We looked for evidence of extra-adrenal production of this and other corticosteroids in 10 subjects stable on long-term glucocorticoid replacement following bilateral adrenalectomy.<p></p> <b>Methods:</b>  In phase 1, patients were maintained on cortisol alone (30 mg/day), in phase 2 dexamethasone (2 mg/day), and in phase 3, both cortisol and dexamethasone. Each phase lasted 3 days.<p></p> <b>Measurements:</b>  On the last day of each phase, 24-h urine collection was performed for analysis of steroid metabolite excretion [using gas chromatography–mass spectrometry (GCMS)] and plasma aldosterone and renin were measured (by radioimmunoassay).<p></p> <b>Results:</b>  Cortisol metabolite excretion rate [tetrahydrocortisone (THE) + tetrahydrocortisol (THF) + allotetrahydrocortisol (aTHF)] fell from 9169 nmol/24 h in phase 1 to 22 nmol/24 h in phase 2, rising to 6843 nmol/24 h in phase 3. Tetrahydroaldosterone (THAldo) excretion was readily detectable and did not alter significantly between phases (26•5, 23•5 and 28•5 nmol/24 h, respectively; P = 0•474). 18-Hydroxycortisol (18-OHF) excretion was easily detectable in phases 1 and 3 (252•5 and 212 nmol/24 h), falling in phase 2 (12 nmol/24 h). 18-oxoF excretion rates were lower but followed a similar pattern (1•62, 0•085 and 1•785 nmol/24 h in phases 1, 2 and 3, respectively).<p></p> <b>Conclusions:</b>  Significant levels of adrenal steroids are found in adrenalectomized subjects. We speculate that this occurs at extra-adrenal sites or in residual adrenal cortex tissue in an ACTH-independent manner. Our data suggest that aldosterone synthase, acting on cortisol, is the source of 18-oxoF and 18-OHF in these subjects. Further studies of corticosteroid production within adrenalectomized subjects, looking for evidence of adrenal regrowth or residual adrenal tissue, are justified.<p></p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Davies, Professor Eleanor and Connell, Professor John and Freel, Dr Marie and Fraser, Prof Robert
Authors: Freel, E.M., Bernhardt, M., Ingram, R., Wallace, A.M., Fraser, R., Davies, E., and Connell, J.M.C.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Clinical Endocrinology
Publisher:Society for Endocrinology
ISSN:0300-0664
ISSN (Online):1365-2265
Published Online:23 March 2007
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
392521Regulation of aldosterone and cortisol synthesis in hypertension and cardiovascular diseaseEleanor DaviesMedical Research Council (MRC)G0400874Institute of Cardiovascular and Medical Sciences
392522Regulation of aldosterone and cortisol synthesis in hypertension and cardiovascular diseaseEleanor DaviesMedical Research Council (MRC)G0400874Institute of Cardiovascular and Medical Sciences