ISSN:
1432-1440
Schlagwort(e):
Cortisol secretion
;
11β-hydroxylation
;
Ketoconazole
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Summary We investigated basal and ACTH stimulated levels of cortisol, corticosterone, 17α-hydroxyprogesterone, 11-deoxycortisol and 11-deoxycorticosterone as well as plasma levels of ACTH before and during the oral administration of ketoconazole in five patients with Cushing's syndrome (3 with bilateral adrenal hyperplasia, 1 with adrenal adenoma and 1 with adrenal carcinoma) and in three controls. The influence of ketoconazole on the transformation of3H-17α-hydroxyprogesterone to3H-11-deoxycortisol and3H-cortisol and of3H-11-deoxycortisol to3H-cortisol as well as of3H-11-deoxycorticosterone to3H-corticosterone was also examined in slices or homogenates of normal and hyperplastic adrenal tissue from four patients. Ketoconazole induced a rise of 11-deoxycortisol and 11-deoxycorticosterone, but not of cortisol and inconsistantly of corticosterone which were increased by ACTH. Thus the ratio 11-deoxycortisol/cortisol rose more after ketoconazole than after ACTH and the ratio 11-deoxycorticosterone/corticosterone rose after ketoconazole but fell after ACTH. Plasma ACTH levels were stimulated 2–50 fold by ketoconazole. Incubation studies of adrenal tissue slices with3H-17α-hydroxyprogesterone showed that ketoconazole inhibited the transformation of3H-17α-hydroxyprogesterone to3H-cortisol but not to3H-11-deoxycortisol so that the ratio3H-11-deoxycortisol/3H-cortisol increased 15–80 fold. After incubation of adrenal slices with3H-11-deoxycortisol or3H-11-deoxycorticosterone and ketoconazole, a 2–260 fold increase of the ratios3H-11-deoxycortisol/3H-cortisol and3H-11-deoxycorticosterone/3H-corticosterone were also found. In conclusion, the in vivo data indicate and the in vitro data confirm that ketoconazole inhibits cortisol and corticosterone secretion by blocking adrenal 11β-hydroxylase activity in normal subjects as well as in patients with Cushing's syndrome, an effect which is compensated in vivo by high ACTH levels.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF01733014
Permalink
