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Endogenous corticosteroid biosynthesis in subjects after bilateral adrenalectomy.
- Source :
-
Clinical endocrinology [Clin Endocrinol (Oxf)] 2007 May; Vol. 66 (5), pp. 659-65. Date of Electronic Publication: 2007 Mar 23. - Publication Year :
- 2007
-
Abstract
- Objective: 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.<br />Methods: 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.<br />Measurements: 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).<br />Results: 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).<br />Conclusions: 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.
- Subjects :
- Adrenal Cortex Diseases metabolism
Adrenal Cortex Hormones blood
Adrenal Cortex Hormones urine
Adult
Aged
Aldosterone blood
Dexamethasone therapeutic use
Female
Gas Chromatography-Mass Spectrometry
Glucocorticoids therapeutic use
Humans
Hydrocortisone analogs & derivatives
Hydrocortisone therapeutic use
Hydrocortisone urine
Male
Middle Aged
Postoperative Period
Radioimmunoassay
Renin blood
Tetrahydrocortisol analogs & derivatives
Tetrahydrocortisol urine
Tetrahydrocortisone urine
Adrenal Cortex Diseases surgery
Adrenal Cortex Hormones biosynthesis
Adrenalectomy
Subjects
Details
- Language :
- English
- ISSN :
- 0300-0664
- Volume :
- 66
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Clinical endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 17381495
- Full Text :
- https://doi.org/10.1111/j.1365-2265.2007.02791.x