PDF(Pubmed)
Abstract：
Newborn screening for congenital adrenal hyperplasia using 17-hydroxyprogesterone by immunoassay remains controversial despite screening been available for almost 40 years. Screening is confounded by poor immunoassay specificity, fetal adrenal physiology, stress, and illness which can result in a large number of false positive screening tests. Screening programmes apply higher screening thresholds based on co-variates such as birthweight or gestational age but the false positive rate using immunoassay remains high. Mass spectrometry was first applied to newborn screening for congenital adrenal hyperplasia over 15 years ago. Elevated 17-hydroxprogesterone by immunoassay can be retested with a specific liquid chromatography tandem mass spectrometry assay that may include additional steroid markers. Laboratories register with quality assurance programme providers to ensure accurate steroid measurements. This has led to improvements in screening but there are additional costs and added laboratory workload. The search for novel steroid markers may inform further improvements to screening. Studies have shown that 11-oxygenated androgens are elevated in untreated patients and that the adrenal steroidogenesis backdoor pathway is more active in babies with congenital adrenal hyperplasia. There is continual interest in 21-deoxycortisol, a specific marker of 21-hydroxylase deficiency. The measurement of androgenic steroids and their precursors by liquid chromatography tandem mass spectrometry in bloodspots may inform improvements for screening, diagnosis, and treatment monitoring. In this review, we describe how liquid chromatography tandem mass spectrometry has improved newborn screening for congenital adrenal hyperplasia and explore how future developments may inform further improvements to screening and diagnosis.
摘要：
尽管筛查已使用近40年，但通过免疫测定使用17-羟基孕酮筛查先天性肾上腺增生的新生儿仍存在争议。筛查被免疫测定特异性差所混淆，胎儿肾上腺生理学，压力，以及可能导致大量假阳性筛查测试的疾病。筛查程序基于协变量如出生体重或胎龄应用较高的筛查阈值，但使用免疫测定的假阳性率仍然很高。15年前，质谱首次应用于新生儿先天性肾上腺增生的筛查。通过免疫测定升高的17-羟基孕酮可以用特定的液相色谱串联质谱测定法重新测试，该测定法可以包括其他类固醇标记。实验室向质量保证计划提供商注册，以确保准确的类固醇测量。这导致了筛查的改进，但也有额外的成本和增加的实验室工作量。寻找新的类固醇标志物可能会进一步改善筛查。研究表明，未经治疗的患者中11-氧合雄激素升高，并且在先天性肾上腺增生的婴儿中，肾上腺类固醇生成后门途径更加活跃。对21-脱氧皮质醇有持续的兴趣，21-羟化酶缺乏症的特异性标记。通过液相色谱串联质谱法在血斑中测量雄激素类固醇及其前体可能会改善筛查，诊断,和治疗监测。在这次审查中,我们描述了液相色谱串联质谱如何改善先天性肾上腺增生的新生儿筛查,并探讨了未来的发展如何进一步改善筛查和诊断.
