Livadas S, Dracopoulou M, Dastamani A, Sertedaki A, Maniati-Christidi M, Magiakou A-M, Kanaka-Gantenbein C, Chrousos G P, Dacou-Voutetakis C
First Department of Pediatrics, Division of Endocrinology, Diabetes and Metabolism, School of Medicine, "Aghia Sophia" Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Clin Endocrinol (Oxf). 2015 Apr;82(4):543-9. doi: 10.1111/cen.12543. Epub 2014 Aug 3.
Nonclassical congenital adrenal hyperplasia (NC-CAH) is caused by mutations of the CYP21A2 gene. The clinical manifestations and hormonal derangements of NC-CAH are quite variable.
(i) To define the phenotype and its relation to genotype according to gender and age and (ii) to evaluate the validity of currently applied hormonal criteria for establishing the diagnosis of NC-CAH.
The clinical, hormonal and molecular data of 280 subjects (235 female) with NC-CAH and a median age of 17·6 years were analysed. CYP21A2 genotyping was performed in all subjects.
The majority of females aged less than 8 years presented with premature pubarche (88·3%), while those older than 8 presented with a polycystic ovary-like phenotype (63·2%). A total of 7·7% of the females and 51·1% of the males were asymptomatic at the time of diagnosis. In the total group, 50·4% of the subjects were compound heterozygotes for one classical (C) and one nonclassical (NC) mutation, while 46% of the alleles studied carried the p.V281L mutation. Basal 17OHP values were below 6 nm (2 ng/ml) in 2·1% of the subjects with NC-CAH, but none had peak 17OHP values post-ACTH lower than 30 nm (10 ng/ml).
NC-CAH has a variable phenotype depending on the age, gender and the presence of a classical mutation. A peak cut-off value of 17OHP post-ACTH lower than 30 nm excludes the diagnosis of NC-CAH, whereas basal 17OHP <6 nm may represent a false-negative result. A significant number of patients harboured a classical mutation, a finding which requires genotyping of the partner for genetic counselling.
非经典型先天性肾上腺皮质增生症（NC-CAH）由CYP21A2基因突变引起。NC-CAH的临床表现和激素紊乱情况差异很大。
（i）根据性别和年龄确定其表型及其与基因型的关系，（ii）评估目前应用的激素标准在诊断NC-CAH中的有效性。
分析了280例NC-CAH患者（235例女性）的临床、激素和分子数据，中位年龄为17.6岁。对所有受试者进行CYP21A2基因分型。
大多数8岁以下女性表现为青春期过早出现阴毛（88.3%），而8岁以上女性表现为多囊卵巢样表型（63.2%）。诊断时，共有7.7%的女性和51.1%的男性无症状。在整个研究组中，有50.4%的受试者为一个经典（C）突变和一个非经典（NC）突变的复合杂合子，而所研究的等位基因中有46%携带p.V281L突变。2.1%的NC-CAH患者基础17OHP值低于6 nmol/L（2 ng/ml），但促肾上腺皮质激素刺激后17OHP峰值均不低于30 nmol/L（10 ng/ml）。
NC-CAH具有可变的表型，取决于年龄、性别和经典突变的存在。促肾上腺皮质激素刺激后17OHP峰值低于30 nmol/L可排除NC-CAH的诊断，而基础17OHP<6 nmol/L可能代表假阴性结果。大量患者携带经典突变，这一发现要求对其配偶进行基因分型以进行遗传咨询。
