Wudy S A, Dörr H G, Solleder C, Djalali M, Homoki J
Department of Pediatrics, University of Ulm, Germany.
J Clin Endocrinol Metab. 1999 Aug;84(8):2724-8. doi: 10.1210/jcem.84.8.5870.
Using routine stable isotope dilution/gas chromatography-mass spectrometry, 17-hydroxyprogesterone, androstenedione, testosterone, dehydroepiandrosterone, androstanediol, and 5alpha-dihydrotestosterone have been profiled in amniotic fluid of midgestation in 77 normal fetuses and 38 untreated or dexamethasone-treated fetuses at risk for 21-hydroxylase deficiency. Dexamethasone was suspended 5-7 days before amniocentesis. In normal fetuses, amniotic fluid concentrations (median, range; nanograms per mL) of 17-hydroxyprogesterone did not reveal a sex difference (1.48, 0.21-4.96), whereas those of androstenedione were lower in females (0.53, 0.00-2.71) than in males (0.93, 0.29-1.98). Testosterone levels were higher in males (0.24, 0.00-0.50) than in females (0.00, 0.00-0.27). No sex difference was found for dehydroepiandrosterone (0.47, 0.19-1.77). Levels of androstanediol and 5alpha-dihydrotestosterone were below the detection limit of our method in most cases. Regarding prenatal diagnosis of 21-hydroxylase deficiency, 17-hydroxyprogesterone and androstenedione presented the diagnostically most valuable steroids and were of equal diagnostic potential. They permitted successful diagnosis in 36 of 37 fetuses at risk: 12 were untreated and unaffected, 13 were treated and unaffected, 4 were untreated and affected (3 salt wasters and 1 simple virilizer), and 8 were treated and affected (5 salt wasters and 3 simple virilizers). In the latter group, one simple virilizer revealed normal steroid concentrations. Isotope dilution/gas chromatography-mass spectrometry, providing the highest specificity in steroid analysis, is proposed for routine use in clinical steroid analysis whenever maximal reliability is requested. Our study provides the first mass spectrometric reference data on amniotic fluid steroid concentrations and underscores the high accuracy of prenatal hormonal diagnosis of 21-hydroxylase deficiency.
利用常规稳定同位素稀释/气相色谱 - 质谱分析法，对77例正常胎儿以及38例有21 - 羟化酶缺乏风险且未经治疗或经地塞米松治疗的胎儿的妊娠中期羊水样本中的17 - 羟孕酮、雄烯二酮、睾酮、脱氢表雄酮、雄烷二醇和5α - 双氢睾酮进行了分析。在羊膜穿刺术前5 - 7天停用了地塞米松。在正常胎儿中，17 - 羟孕酮的羊水浓度（中位数，范围；纳克/毫升）未显示出性别差异（1.48，0.21 - 4.96），而雌二醇的浓度在女性中（0.53，0.00 - 2.71）低于男性（0.93，0.29 - 1.98）。睾酮水平在男性中（0.24，0.00 - 0.50）高于女性（0.00，0.00 - 0.27）。脱氢表雄酮未发现性别差异（0.47，0.19 - 1.77）。在大多数情况下，雄烷二醇和5α - 双氢睾酮的水平低于我们方法的检测限。关于21 - 羟化酶缺乏的产前诊断，17 - 羟孕酮和雄烯二酮是诊断价值最高的类固醇，且具有同等的诊断潜力。它们在37例有风险的胎儿中成功诊断出36例：12例未经治疗且未受影响，13例经治疗且未受影响，4例未经治疗且受影响（3例失盐型和1例单纯男性化型），8例经治疗且受影响（5例失盐型和3例单纯男性化型）。在后一组中，1例单纯男性化型胎儿的类固醇浓度显示正常。同位素稀释/气相色谱 - 质谱分析法在类固醇分析中具有最高的特异性，建议在需要最大可靠性时用于临床类固醇分析的常规检测。我们的研究提供了关于羊水类固醇浓度的首批质谱参考数据，并强调了21 - 羟化酶缺乏产前激素诊断的高度准确性。
