Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

At Cochin Hospital in Paris, France, ten 21-29 year old normal male volunteers received either 200 mg RU-486 per day or a placebo for 8 consecutive days between 8:00 and 9:00 in the morning, then went through a 28-day washout period before receiving what they did not receive the first time for 8 days. The researchers wanted to examine the antiglucocorticoid effect of RU-486, any evidence of peripheral cortisol deprivation, and the adrenocortical and corticotroph reserves. An assessment of potential risk of longterm administration of RU-486 is needed to determine whether it can be used to treat chronic diseases (e.g., meningioma and breast cancer). RU-486 was responsible for overreaction of the pituitary-adrenal axis (8:00 am plasma cortisol, 147.3 ng/mL vs. 257.6 ng/mL; 8:00 am salivary cortisol, 5.8 ng/mL vs. 15.2 ng/mL; nocturnal urinary cortisol, 8.4 mcg vs. 33.7 mcg; and 8:00 am plasma adrenocorticotropic hormone [ACTH] 29.2 pg/mL vs. 60.2 pg/mL). All these changes differed significantly from those during placebo treatment (0.0001 p 0.03). These changes no longer existed 4 days after the end of treatment. The men kept a daily record of subjective clinical symptoms, body weight and temperature, blood pressure, and heart rate, which did not indicate any side effects or any considerable variation during treatment. RU-486 did not affect blood electrolyte and eosinophil counts. Blood glucose levels during fasting were somewhat higher at the end of treatment (p = 0.04). During RU-486 treatment, the adrenocortical response to 0.25 mg of intramuscularly injected Cortrosyn was amplified (peak values before and after, plasma cortisol, 272.5 ng/mL vs. 347.1 ng/mL; 17 ng/mL vs. 31.1 ng/mL) (p 0.006). Direct stimulation of the pituitary resulted in exaggerated corticotroph and adrenocortical responses (p 0.005). These findings showed that a daily dose of 200 mg RU-486 causes a hormonally detectable antiglucocorticoid effect but no clinical symptoms.
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PMID:Administration of RU 486 for 8 days in normal volunteers: antiglucocorticoid effect with no evidence of peripheral cortisol deprivation. 810 25

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.
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PMID:Adrenal effects of low-dose aminoglutethimide when used alone in postmenopausal women with advanced breast cancer. 820 61