Endocrine Abstracts

HPA response to glucocorticoids (GCs) feedback is usually tested by dexamethasone (DEX), a synthetic GC; it poorly crosses BBB and preferentially activates pituitaric glucocorticoid receptor (GR), with a binding potency to GR 7 fold higher and an anti-inflammatory potency about 35 fold higher than cortisol. Cortisol, which easily penetrates into CNS, could better evaluate the GC feedback by acting also at supra-pituitary level. We studied the effects of 150 min infusion of hydrocortisone (HC: 15, 30 or 60 μg/kg/h) or DEX (0.4, 0.8, 1.6 or 2.1, 4.2, 8.5 μg/kg/h, covering either HC:DEX 1:35 or 1:7) on ACTH and cortisol levels in 9 normal subjects who underwent also a testing session with placebo. The study had been approved by an independent Ethical Committee. During placebo, ACTH and cortisol levels showed progressive decrease (P<0.05). The different doses of HC induced dose-dependent cortisol increases (P<0.05) coupled with dose-dependent ACTH decreases (P<0.05). 0.4, 0.8 and 1.6 μg/kg/h DEX doses did not modify cortisol levels; 0.8 and 1.6 but not 0.4 μg/kg/h DEX doses induced a dose-dependent ACTH decrease (P<0.05). Conversely, 2.1, 4.2 and 8.5 μg/kg/h DEX doses inhibited cortisol levels in dose-dependent manner (P<0.05) and induced more marked ACTH decrease (P<0.05). In conclusion, based on the potency of binding to GR, similar doses of hydrocortisone and dexamethasone are needed to reduce ACTH levels. Conversely, taking into account the anti-inflammatory potency, doses of dexamethasone higher than hydrocortisone are needed to inhibit ACTH secretion. These latter findings are likely to reflect different sites where natural and synthetic GCs exert their feedback action, i.e. mainly the CNS for hydrocortisone and the pituitary for dexamethasone. It is suggested that the HPA sensitivity to the feedback action of GCs in various pathophysiological conditions would better be evaluated by using natural GCs.