Steroid Research & Mass Spectrometry Unit, Laboratory for Translational Hormone Analytics, Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany.
Steroid Research & Mass Spectrometry Unit, Laboratory for Translational Hormone Analytics, Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany.
J Steroid Biochem Mol Biol. 2018 Apr;178:221-228. doi: 10.1016/j.jsbmb.2017.12.016. Epub 2017 Dec 23.
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-, 17α-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 5α-dihydrotestosterone, for urinary metabolites of dehydroepiandrosterone (DHEA), and for 11β-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 (β = 0.379; P =.0006), followed by A4 (β = 0.280; P = .0008)) and 17OHP (β = 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.
肾上腺雄激素过多是经典先天性肾上腺皮质增生症（CAH）的标志，这是由于 21-羟化酶缺乏所致。最近，在 CAH 患者中发现了一类具有高度活性的肾上腺衍生雄激素，即 11-氧代 C19 类固醇。我们的研究目的是阐明 CAH 儿童中 11-氧代雄激素的意义。我们回顾性分析了 99 例年龄在 3.0-10.9 岁的经典 CAH 儿童，他们在接受氢化可的松和氟氢可的松治疗时，通过气相色谱-质谱法测定了 190 天的糖皮质激素、17α-羟孕酮（17OHP）和雄激素代谢产物的日尿排泄率。使用健康儿童的参考值，将每日尿类固醇代谢产物排泄转化为 z 分数。分别计算雄甾酮（AN）、雄烯二酮（A4）的主要尿代谢产物、睾酮和 5α-二氢睾酮、去氢表雄酮（DHEA）的代谢产物以及肾上腺衍生 11-氧代雄激素的主要尿代谢产物 11β-羟基雄甾酮（11OHAN）的雄激素代谢产物 z 分数。应用多元回归分析来分析 11OHAN 合成的前体。在接受治疗的 CAH 儿童中，11OHAN、皮质醇和 17OHP 代谢产物 z 分数升高，而 AN 和 DHEA 代谢产物 z 分数正常或受抑制。多元回归分析显示，11OHAN 排泄与 21-脱氧皮质醇（β=0.379；P=.0006）最强相关，其次是 A4（β=0.280；P=.0008）和 17OHP（β=0.243；P=.04）代谢产物排泄。接受治疗的 CAH 儿童的雄激素过多仅归因于升高的 11-氧代雄激素，这些雄激素除了已知来自 A4 的转化外，还来自直接来自 21-脱氧皮质醇的转化。11-氧代雄激素可能比传统雄激素更好地反映肾上腺雄激素状态和治疗反应的生物标志物。
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