Androgen excess is due to elevated 11-oxygenated androgens in treated children with congenital adrenal hyperplasia

作者：Kamrath Clemens; Wettstaedt Lisa; Boettcher Claudia; Hartmann Michaela F; Wudy Stefan A^*

来源：Journal of Steroid Biochemistry and Molecular Biology, 2018, 178: 221-228.

DOI：10.1016/j.jsbmb.2017.12.016

• Urine
• Steroid
• CAH
• Congenital adrenal hyperplasia
• 21-hydroxylase deficiency
• 11-oxygenated androgens

Adrenal androgen excess is the hallmark of classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Recently, 11-oxygenated C19 steroids, a class of highly active adrenal-derived androgens, have been described in patients with CAH.
The aim of our study was to elucidate the significance of 11-oxygenated androgens in children with CAH.
We retrospectively analysed 190 daily urinary excretion rates of glucocorticoid-, 17 alpha-hydroxyprogesterone (17OHP)-, and androgen metabolites determined by gas chromatography-mass spectrometry of 99 children aged 3.0-10.9 years with classic CAH on hydrocortisone and fludrocortisone treatment. Daily urinary steroid metabolite excretions were transformed into z-scores using references of healthy children. Androgen metabolite z-scores were separately calculated for androsterone (AN), the major urinary metabolite of androstenedione (A4), testosterone and 5 alpha-dihydrotestosterone, for urinary metabolites of dehydroepiandrosterone (DHEA), and for 11 beta-hydroxyandrosterone (11OHAN), the major urinary metabolite of adrenal-derived 11-oxygenated androgens. Multivariate regression analysis was applied to analyse the precursors of 11OHAN synthesis.
11OHAN, cortisol-, and 17OHP metabolite z-scores were elevated in treated children with CAH, whereas AN and DHEA metabolite z-scores were normalized or suppressed. Multivariate regression analysis revealed that 11OHAN excretion was strongest associated with 21-deoxycortisol (beta = 0.379; P = .0006), followed by A4 (beta = 0.280; P = .0008)) and 17OHP (beta = 0.243; P = .04) metabolite excretion.
Androgen excess in treated children with CAH is solely due to elevated 11-oxygenated androgens that derive in addition to the known conversion from A4 also by direct conversion from 21-deoxycortisol. 11-Oxygenated androgens may represent better biomarkers of adrenal androgen status and treatment response than conventional androgens.

• 出版日期2018-4