Adrenal effects of low-dose aminoglutethimide when used alone in postmenopausal women with advanced breast cancer.
Aminoglutethimide (Ag) is a potent aromatase-enzyme inhibitor used in the treatment of patients with breast cancer. In the past, it has been administered in doses of 1,000 mg/d (usually with 40 mg hydrocortisone). At these dose levels, the drug also affects multiple cytochrome P-450 enzymes, including enzymes for adrenal steroid biosynthesis. Recently, lower-dose regimens (500 mg/d) of Ag have been found to be just as effective for breast cancer therapy, but less toxic than the higher conventional dose. There is limited information on the adrenal effects at the lower dosages, and it is not known whether these effects are clinically significant. We measured basal and synthetic corticotropin (Cortrosyn)-stimulated levels of adrenal steroids in postmenopausal breast cancer patients before and during treatment with low-dose Ag (500 mg/d) administered without a glucocorticoid preparation. Basal levels of progesterone, 17-OH progesterone, and 11-deoxycortisol were higher after 2 months' treatment (P < .01). After ACTH injection, peak levels of progesterone and 17-OH progesterone were higher (P < .01), but in contrast, peak levels of 18-OH corticosterone were lower during treatment (P < .02). Basal and peak levels of cortisol, aldosterone, and all other adrenal steroids were unchanged during treatment. We conclude that low-dose Ag treatment leads to partial inhibition of the 21-hydroxylase, 11-hydroxylase, and 18-hydroxylase adrenal enzymes. Since cortisol and aldosterone secretion remained normal with minimal shunting to or accumulation of adrenal androgen compounds, we believe that the mild inhibition was compensated for by further endogenous ACTH stimulation.
Carella
M J
MJ
Department of Medicine, Michigan State University, East Lansing 48824-1317.
Dimitrov
N V
NV
Gossain
V V
VV
Srivastava
L
L
Rovner
D R
DR
D019326:17-alpha-Hydroxyprogesterone; D000311:Adrenal Glands / Q000187:drug effects*; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000616:Aminoglutethimide / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006908:Hydroxyprogesterones / Q000097:blood; D008875:Middle Aged; D017698:Postmenopause; D011374:Progesterone / Q000097:blood
D006908:Hydroxyprogesterones; D000616:Aminoglutethimide; D000450:Aldosterone; D011374:Progesterone; D019326:17-alpha-Hydroxyprogesterone; D006854:Hydrocortisone