Influence of ACTH on aminoglutethimide induced reduction of plasma steroids in postmenopausal breast cancer.
In postmenopausal women estrogens are mainly produced by aromatase mediated conversion of adrenal 4-ene-steroids in peripheral tissue, a process which is inhibited by aminoglutethimide (AG). To assess possible fluctuations in adrenocortical steroid secretion and the impact on plasma estrogen levels the effect of physiological ACTH doses was studied in 24 postmenopausal women with advanced breast cancer treated with AG 4 X 250 mg and hydrocortisone 2 X 10 + 1 X 20 mg daily. Synthetic 1-24 ACTH (Synacthen) 0.5 mg was injected i.m. at 8.30 a.m. (t0), 10 h after the last AG + hydrocortisone dose. A definite decrease of t0 levels of the 5-ene-steroids dehydroepiandrosterone and its sulphate, and androstenediol was found at 1 month, with no further decrease at 2 months. 5-Ene-steroids responded decreasingly to ACTH under treatment. The 4-ene-steroids progesterone, androstenedione and testosterone, before and after ACTH were not suppressed by 1 or 2 months of treatment. Basal (t0) cortisol remained normal. Cortisol response to ACTH (delta max) was drastically diminished, but still present. Plasma estrogens were decreased. Estradiol (E2) at t0, being low from the start, fell by 50%. Estrone (E1) at t0 dropped to 30%. ACTH had measurable influence on E2, but did cause a transient increase of E1 (mean delta max 40% of baseline value) under treatment. The following conclusions are drawn: Treatment with AG + hydrocortisone for postmenopausal breast cancer reduces plasma estrogens, particularly E1. Plasma E1 reduction is not stable as demonstrated by the response to a physiological ACTH dose. The responses of 4-ene-steroids to ACTH are not affected by treatment, except for the response of cortisol which is significantly diminished.
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives*; D000616:Aminoglutethimide / Q000097:blood / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D003366:Cosyntropin / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004967:Estrogens / Q000097:blood; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000627:therapeutic use; D008593:Menopause; D009376:Neoplasms, Hormone-Dependent / Q000097:blood / Q000188:drug therapy*; D011863:Radioimmunoassay; D013256:Steroids / Q000097:blood*
D004967:Estrogens; D013256:Steroids; D000616:Aminoglutethimide; D003366:Cosyntropin; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone