Corticosteroids can be synthesised in tissues other than the adrenal cortex but the contribution of this extra-adrenal corticosteroidogenesis to circulating levels in man is not known. We studied this in a group 10 subjects taking chronic glucocorticoid replacement following bilateral adrenalectomy. In phase 1, they were maintained on cortisol alone (30 mg/day). In phase 2, cortisol was replaced by dexamethasone (2 mg/day) and in phase 3, they received both cortisol and dexamethasone. Each phase lasted 3 days. A 24 h urine collection was made on the last day of each phase for analysis of steroid metabolite excretion by GCMS. Local ethics committee approval was obtained.
Cortisol metabolite excretion rate (THE+THF+aTHF) fell from 9169 nmol/24 hr in phase 1 to 22 nmol/24 hr in phase 2 rising to 6843 nmol/24 hr in phase 3. Tetrahydroaldosterone excretion was low but detectable and did not alter significantly between phases (26.5, 23.5 and 28.5 nmol/24 hr respectively; P=0.474). In contrast, 18-hydroxycortisol (18-OHF) excretion was higher than in normal subjects in phases 1 and 3 (252.5 & 212 nmol/24/hr), falling substantially in phase 2 (12 nmol/24 hr).
Easily detectable amounts of aldosterone are synthesised in subjects who have undergone bilateral adrenalectomy. We conclude that this occurs at extra-adrenal sites, or in residual adrenal cortex tissue in an ACTH-independent manner. Synthesis of 18-OHF is entirely dependent on exogenous cortisol which must be 18-hydroxylated by 11β-hydroxylase or aldosterone synthase again either in residual or extra-adrenal tissue. This agrees with our previous report in normal subjects1. The high levels of 18-OHF in phase 1 may indicate some post-adrenalectomy induction of these enzymes. Finally, the low, but detectable, excretion of cortisol metabolites in phase 2 also represents endogenous synthesis. Further studies of corticosteroid production within adrenalectomized subjects, particularly looking for evidence of adrenal re-growth or residual adrenal tissue, are clearly justified.
1. Freel EM et al. Studies on the origin of circulating 18-hydroxycortisol and 18-oxocortisol in normal subjects JCEM 89: 462833, 2004