RECOVERY FROM GLUCOCORTICOID INHIBITION OF THE RESPONSES TO CORTICOTROPHIN‐RELEASING HORMONE

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Abstract
We have characterized the recovery of the hypothalamic-pituitary-adrenal (HPA) axis from inhibition by short-term prednisolone administration. Prednisolone was given in a dosage averaging 25 mg at 12 h intervals orally for up to 2 weeks to adult volunteers. Human corticotrophin releasing hormone (hCRH) tests were performed at 0901 h using a bolus injection of 1 .mu.g/kg before and 24-48 h after discontinuing the prednisolone. In the initial control study, hCRH stimulated a two-fold rise in plasma ACTH and a 30% rise in plasma cortisol within 30 min (ACTH rose from 18.5 .+-. 4.5, SEM, pg/ml to 36.5 .+-. 12.6 pg/ml and cortisol from 415 .+-. 58 to 531 .+-. 69 nmol/l in response to hCRH). One dose of prednisolone had no effect on the ACTH or cortisol response to hCRH administered 24 h later. Twenty-four hours after discontinuing a 1 week course of prednisolone, baseline plasma ACTH (3.9 .+-. 0.6 pg/ml) and cortisol (146 .+-. 17 nmol/l) were markedly suppressed, as was the cortisol response to hCRH (peak 198 .+-. 22). However, the plasma ACTH resposne to hCRH was not significantly suppressed. Forty-eight hours after discontinuing prednisolone, the recovery of ACTH secretion was complete (baseline 10.9 .+-. 4.2, peak 36.4 .+-. 14.8 pg/ml), but the cortisol response to hCRH was still depressed (peak 294 .+-. 66 nmol/l). Recovery from a 2 week course of prednisolone had similar characteristics except plasma cortisol was depressed more profoundly. Plasma dehydroepiandrosterone (DHA) during hCRH tests and dehydroepiandrosterone sulphate (DHAS) paralleled plasma cortisol. We interpret these data suggest that the sequence of recovery from 1 to 2 weeks of glucocorticoid inhibition is characterized first by return to normal of ACTH secretion, followed by sequential returns to normal of CRH and adrenal steroid secretion. During recovery from this relatively short course of glucocorticoids, the events reported to be characteristic of withdrawal from chronic glucocorticoid therapy appear to occur in foreshortened sequence.