Endogenous corticosteroid biosynthesis in subjects after bilateral adrenalectomy.
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.


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.


METHODS
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).


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).


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.
Freel
E M
EM
Glasgow Cardiovascular Research Centre, University of Glasgow, UK.
Bernhardt
R
R
Bernhardt
M
M
Ingram
M
M
Ingram
R
R
Wallace
A M
AM
Fraser
R
R
Davies
E
E
Connell
J M C
JM
D000303:Adrenal Cortex Diseases / Q000378:metabolism / Q000601:surgery*; D000305:Adrenal Cortex Hormones / Q000096:biosynthesis* / Q000097:blood / Q000652:urine; D000315:Adrenalectomy; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D003907:Dexamethasone / Q000627:therapeutic use; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000627:therapeutic use / Q000652:urine; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D011863:Radioimmunoassay; D012083:Renin / Q000097:blood; D013760:Tetrahydrocortisol / Q000031:analogs & derivatives / Q000652:urine; D013761:Tetrahydrocortisone / Q000652:urine
D000305:Adrenal Cortex Hormones; D005938:Glucocorticoids; C038135:18-oxocortisol; C006461:allotetrahydrocortisol; D000450:Aldosterone; D013761:Tetrahydrocortisone; D013760:Tetrahydrocortisol; D003907:Dexamethasone; D012083:Renin; C033689:18-hydroxycortisol; D006854:Hydrocortisone