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 > School of Cardiovascular & Metabolic Health |
| Journal Name: | Clinical Endocrinology |
| Publisher: | Society for Endocrinology |
| ISSN: | 0300-0664 |
| ISSN (Online): | 1365-2265 |
| Published Online: | 23 March 2007 |
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