cortodoxone and 11-beta-hydroxyandrosterone

Using GLC, multiple adrenal corticosteroid urinary metabolites, including androgenic-anabolic, glucocorticoid, pregnanediol, and pregnanetriol, were measured in eight ambulatory female RA patients and eight matched normal control subjects on baseline, ACTH-, and metyrapone-stimulation days under carefully monitored clinical research center protocol. Neither group had been treated previously with any steroid hormones. The 11-deoxy-17-KS metabolites, derived from adrenal androgenic-anabolic steroids, and comprising androsterone, etiocholanolone, and DHA, were significantly lower in RA patients on baseline (P less than .001), ACTH (P less than .005)-, and metyrapone (P less than .02)-stimulation days. To the contrary, the 11-oxy-17-KS metabolites, derived mainly from glucocorticoids, showed some lowered excretion at baseline (P less than .05), but none on ACTH- or metyrapone-stimulation. RA patients had lower tetrahydrocortisone (P less than .001) and tetrahydro-11-deoxycortisol (P less than .01) excretion at baseline, but not during ACTH- or metyrapone-stimulation, than control subjects. Pregnanetriol excretion was lower (P less than .005) in RA patients than control subjects only during ACTH-stimulation. No difference was found between groups in tetrahydrocortisol or pregnanediol excretion on any day studied. Under conditions of oral metyrapone administration (750 mg every four hours for seven doses) each control subject increased their DHA excretion, but no RA patient showed an increase over baseline excretion (P less than .02). Except for 11-deoxy-17-KS, no difference was found in the other metabolites studied during metyrapone stimulation, ie, pregnanediol, pregnanetriol, tetrahydro-11-deoxycortisol, and tetrahydrocortisol. The 24-hour oral metyrapone test provided a greater stimulus to total 11-deoxy-17-KS excretion than an eight-hour intravenous ACTH test in control and particularly RA (P less than .01) subjects even though the DHA excretion decreased in the RA groups. Our findings of lower adrenal androgenic-anabolic metabolite excretion in female RA patients than normal matched control subjects under various conditions and other supportive androgenic hormone and metabolite studies reviewed in the English reports suggest an abnormality of adrenal androgen synthesis or metabolism in RA, whether it be a primary predisposing or secondary factor in disease. The recognized female sex preponderance and age-specific patterns of occurrence of RA are consiste

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Anabolic Agents; Androgens; Androsterone; Arthritis, Rheumatoid; Calorimetry; Chromatography, Gas; Cortodoxone; Dehydroepiandrosterone; Etiocholanolone; Female; Glucocorticoids; Humans; Metyrapone; Middle Aged; Pregnanediol; Pregnanetriol

The classic androgen synthesis pathway proceeds via dehydroepiandrosterone, androstenedione, and testosterone to 5α-dihydrotestosterone. However, 5α-dihydrotestosterone synthesis can also be achieved by an alternative pathway originating from 17α-hydroxyprogesterone (17OHP), which accumulates in congenital adrenal hyperplasia (CAH). Similarly, recent work has highlighted androstenedione-derived 11-oxygenated 19-carbon steroids as active androgens, and in CAH, androstenedione is generated directly from 17OHP. The exact contribution of alternative pathway activity to androgen excess in CAH and its response to glucocorticoid (GC) therapy is unknown.. We sought to quantify classic and alternative pathway-mediated androgen synthesis in CAH, their diurnal variation, and their response to conventional GC therapy and modified-release hydrocortisone.. We used urinary steroid metabolome profiling by gas chromatography-mass spectrometry for 24-hour steroid excretion analysis, studying the impact of conventional GCs (hydrocortisone, prednisolone, and dexamethasone) in 55 adults with CAH and 60 controls. We studied diurnal variation in steroid excretion by comparing 8-hourly collections (23:00-7:00, 7:00-15:00, and 15:00-23:00) in 16 patients with CAH taking conventional GCs and during 6 months of treatment with modified-release hydrocortisone, Chronocort.. Patients with CAH taking conventional GCs showed low excretion of classic pathway androgen metabolites but excess excretion of the alternative pathway signature metabolites 3α,5α-17-hydroxypregnanolone and 11β-hydroxyandrosterone. Chronocort reduced 17OHP and alternative pathway metabolite excretion to near-normal levels more consistently than other GC preparations.. Alternative pathway-mediated androgen synthesis significantly contributes to androgen excess in CAH. Chronocort therapy appears superior to conventional GC therapy in controlling androgen synthesis via alternative pathways through attenuation of their major substrate, 17OHP.

Topics: 17-alpha-Hydroxypregnenolone; Adolescent; Adrenal Hyperplasia, Congenital; Adult; Androgens; Androsterone; Circadian Rhythm; Cortodoxone; Delayed-Action Preparations; Dexamethasone; Female; Gas Chromatography-Mass Spectrometry; Glucocorticoids; Humans; Hydrocortisone; Male; Middle Aged; Prednisolone; Pregnanetriol; Young Adult

To study the effect of endogenous steroids on the presence of uterine leiomyomas.. Urine samples of 27 premenopausal women with leiomyomas and 25 age-matched healthy premenopausal women were collected. The concentration of estrogens and androgens in the urine samples of the two groups were determined using a gas chromatography mass spectrometer and the two groups were compared. To study metabolic changes in patients indirectly, the concentration ratios of precursor metabolite to product metabolite of the two groups were also compared.. Urinary concentrations of 17beta-estradiol, 5-androstene-3beta, 16beta, 17beta, triol, 11-keto-ethiocholanolone, 11beta-hydroxy-androsterone, 11beta-hydroxy-etiocholanolone, THS, THA, THE, alpha-cortol and beta-cortol were significantly higher in patients than in controls. The concentration ratios of 17beta-estradiol/estrone and 11/beta-hydroxy-ethiocholanolone/11beta-hydroxy-androsterone increased in patients.. The presence of uterine leiomyomas correlates with an increase in urinary concentrations of estrogens and androgens, and it appears to be caused by a decrease in patients' metabolism of steroids.

Topics: Adult; Androgens; Androstenols; Androsterone; Case-Control Studies; Corticosterone; Cortodoxone; Dehydroepiandrosterone; Estradiol; Estrogens; Estrone; Etiocholanolone; Female; Gas Chromatography-Mass Spectrometry; Humans; Leiomyoma; Middle Aged; Pregnanes; Premenopause; Tetrahydrocortisone; Uterine Neoplasms