Balsamo Antonio, Baronio Federico, Ortolano Rita, Menabo Soara, Baldazzi Lilia, Di Natale Valeria, Vissani Sofia, Cassio Alessandra
Pediatric Endocrinology Unit, Department of Medical and Surgical Sciences, Endo-ERN Centre IT11, S.Orsola-Malpighi University Hospital, Bologna, Italy.
Genetic Unit, Department of Medical and Surgical Sciences, Endo-ERN Centre IT11, S.Orsola-Malpighi University Hospital, Bologna, Italy.
Front Pediatr. 2020 Dec 22;8:593315. doi: 10.3389/fped.2020.593315. eCollection 2020.
Congenital adrenal hyperplasia includes autosomal recessive conditions that affect the adrenal cortex steroidogenic enzymes (cholesterol side-chain cleavage enzyme; 3β-hydroxysteroid dehydrogenase; 17α-hydroxylase/17,20 lyase; P450 oxidoreductase; 21-hydroxylase; and 11β-hydroxylase) and proteins (steroidogenic acute regulatory protein). These are located within the three major pathways of the steroidogenic apparatus involved in the production of mineralocorticoids, glucocorticoids, and androgens. Many countries have introduced newborn screening program (NSP) based on 17-OH-progesterone (17-OHP) immunoassays on dried blood spots, which enable faster diagnosis and treatment of the most severe forms of 21-hydroxylase deficiency (21-OHD). However, in several others, the use of this diagnostic tool has not yet been implemented and clinical diagnosis remains challenging, especially for males. Furthermore, less severe classic forms of 21-OHD and other rarer types of CAHs are not identified by NSP. The aim of this mini review is to highlight both the main clinical characteristics and therapeutic options of these conditions, which may be useful for a differential diagnosis in the neonatal period, while contributing to the biochemical evolution taking place in the steroidogenic field. Currently, chromatographic techniques coupled with tandem mass spectrometry are gaining attention due to an increase in the reliability of the test results of NPS for detecting 21-OHD. Furthermore, the possibility of identifying CAH patients that are not affected by 21-OHD but presenting elevated levels of 17-OHP by NSP and the opportunity to include the recently investigated 11-oxygenated androgens in the steroid profiles are promising tools for a more precise diagnosis and monitoring of some of these conditions.
先天性肾上腺增生包括常染色体隐性疾病，这些疾病会影响肾上腺皮质类固醇生成酶（胆固醇侧链裂解酶；3β-羟基类固醇脱氢酶；17α-羟化酶/17,20裂解酶；P450氧化还原酶；21-羟化酶；以及11β-羟化酶）和蛋白质（类固醇生成急性调节蛋白）。这些位于参与盐皮质激素、糖皮质激素和雄激素生成的类固醇生成装置的三大途径中。许多国家已基于干血斑上的17-羟孕酮（17-OHP）免疫测定法推出了新生儿筛查项目（NSP），这使得能够更快地诊断和治疗最严重形式的21-羟化酶缺乏症（21-OHD）。然而，在其他一些国家，这种诊断工具尚未得到应用，临床诊断仍然具有挑战性，尤其是对男性而言。此外，NSP无法识别不太严重的经典型21-OHD和其他较罕见类型的先天性肾上腺增生。本小型综述的目的是强调这些疾病的主要临床特征和治疗选择，这可能有助于新生儿期的鉴别诊断，同时有助于类固醇生成领域正在发生的生化演变。目前，由于NPS检测21-OHD的测试结果可靠性提高，色谱技术与串联质谱联用正受到关注。此外，通过NSP识别不受21-OHD影响但17-OHP水平升高的先天性肾上腺增生患者的可能性，以及将最近研究的11-氧化雄激素纳入类固醇谱的机会，是更精确诊断和监测其中一些疾病的有前景的工具。
