Escape from dexamethasone-induced ACTH and cortisol suppression by corticotrophin-releasing hormone: modulatory effect of basal dexamethasone levels.

The response of ACTH and cortisol to corticotrophin-releasing hormone (CRH) after pretreatment with various doses of dexamethasone was investigated in five healthy subjects. The five subjects participated in six experiments. In each experiment 200 micrograms ovine CRH was administered as an i.v. bolus injection at 0900 h after pretreatment with respectively: (A) 1 mg dexamethasone orally at 2300 h in the evening before CRH injection, (B) 2 mg dexamethasone orally at 2300 h in the evening before CRH injection, (C) 4 mg dexamethasone orally at 2300 h in the evening before CRH injection, (D) 2 mg dexamethasone orally at 2300 h in the evening before CRH injection, followed by 2 mg dexamethasone orally 1 h before CRH, (E) no dexamethasone and (F) 1 mg dexamethasone orally 1 h before CRH injection. In spite of overnight suppression with a single dose of dexamethasone CRH elicited cortisol rises in all individuals (experiments A-C). Dexamethasone pretreatment in experiment D abolished the CRH-induced stimulation of the pituitary-adrenal axis. There was a significant and negative correlation between the basal dexamethasone levels (i.e. the dexamethasone levels immediately before CRH administration) in the experiments A-D and the areas under the individual ACTH (R = -0.62; P less than 0.01 by Spearman's rank correlation test) and cortisol (R = -0.81; P less than 0.001 by Spearman's test) curves, i.e. the lower the basal dexamethasone levels, the greater the rise in ACTH and cortisol levels after CRH administration.(ABSTRACT TRUNCATED AT 250 WORDS)