Abstract
Etomidate has been shown to inhibit corticosteroid secretion in the normal adrenal gland, but its direct effect in human pathologic adrenals has not been clearly established. In the present study the effect of varying doses of etomidate (10 −11 –10 −5 M) was investigated on basal and adrenocorticotrophic hormone (ACTH)-stimulated corticosteroid secretions in isolated adrenocortical cells obtained from two patients with primary aldosteronism (adenoma and micronodular hyperplasia) and in those from a patient with Cushing's syndrome (adenoma). In cells from primary aldosteronism, increasing concentrations etomidate (10 −11 –10 −5 M) produced a dose-dependent decrease of basal and ACTH-stimulated cortisol, aldosterone, 18-hydroxycorticosterone, and corticosterone secretions (ED 50: 10 −8 M for each of these corticosteroids). In the same cells, the secretions of 11-deoxycortisol and deoxycorticosterone were increased in the presence of low (10 −9 – 10 −7 M) but not high doses of etomidate (10 −6 –10 −5 M). In cells from Cushing's syndrome the changes in costicosteroid secretion were similar to those found in primary aldosteronism except that aldosterone and 18-hydroxycorticosterone could not be determined due to their low levels. Thus the potent inhibition of corticosteroids in human pathologic adrenocortical cells in the presence of low concentrations of etomidate may be predominantly due to inhibition of the 11β-hydroxylase enzyme, whereas higher doses of the drug may inhibit earlier steps of the corticosteroid biosynthetic pathway. (Steroids 58:64–68, 1993)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.