Phenotypic profiling of parents with cryptic nonclassic congenital adrenal hyperplasia: findings in 145 unrelated families.
Phenotypic profiling of parents with cryptic nonclassic congenital adrenal hyperplasia: findings in 145 unrelated families.
复制标题
DOI：
10.1530/eje-11-0019
复制
发表时间：
2011-06
影响因子：
5.8
通讯作者：
Merke DP
中科院分区：
文献类型：
--
作者：
Nandagopal R;Sinaii N;Avila NA;Van Ryzin C;Chen W;Finkielstain GP;Mehta SP;McDonnell NB;Merke DP
通过家族遗传学研究，对非典型先天性肾上腺皮质增生（NCCAH）的父母进行综合表型分析，并确定21-羟化酶缺乏症患者父母中隐性NCCAH的发生率。对145名无血缘关系的先天性肾上腺皮质增生症患者的249名父母进行了基因分型。对有两个CYP 21 A2突变的父母进行了广泛的评估。在249名父母中，有10名（4%; 7名女性和3名男性）被确定为患有隐性NCCAH。大多数是以前报告的NCCAH发病率较高的种族。促肾上腺皮质激素刺激在8个父母提供生化确认（17-羟孕酮范围56-364 nmol/l）和皮质醇反应是500 nmol/l的三个父母（38%）。在7名患有隐性NCCAH的女性（27-54岁）中，4名先前患有不孕症，2名报告月经不规则，2名接受多毛症治疗，1名患有雄激素性脱发。男性无症状。所有隐性NCCAH父母报告青春期正常，身高正常。父母中有两人出现肾上腺肥大和一个小的肾上腺髓性脂肪瘤，未发现睾丸肾上腺剩余组织。父母经基因检测确诊为NCCAH大多无症状。通常观察到暂时性女性不孕和次优皮质醇反应。对于家族基因型研究确定的CAH成人患者，除非有症状，否则不应持续糖皮质激素治疗，但在选择病例时应考虑糖皮质激素应激覆盖。患有CAH的孩子的父母有1：25的风险患有NCCAH;如果患有CAH的孩子的母亲患有不孕症，则需要评估NCCAH。
To comprehensively phenotype parents identified with nonclassic congenital adrenal hyperplasia (NCCAH) by family genetic studies, termed here as cryptic NCCAH and to define the incidence of cryptic NCCAH in the parents of a large cohort of patients with 21-hydroxylase deficiency. Genotyping was performed on 249 parents of 145 unrelated congenital adrenal hyperplasia CAH) patients. Parents with two CYP21A2 mutations underwent extensive evaluation. Of the 249 parents, ten (4%; seven females and three males) were identified as having cryptic NCCAH. The majority was of ethnicities previously reported to have a higher incidence of NCCAH. Cosyntropin stimulation performed in eight parents provided biochemical confirmation (17-hydroxyprogesterone range 56–364 nmol/l) and cortisol response was % 500 nmol/l in three parents (38%). Of the seven women (27–54 years) with cryptic NCCAH, four had prior infertility, two reported irregular menses, two had treatment for hirsutism, one had androgenic alopecia. Men were asymptomatic. All cryptic NCCAH parents reported normal puberty and had normal height. Adrenal hypertrophy and a small adrenal myelolipoma were observed in two parents; testicular adrenal rest tissue was not found. Parents diagnosed with NCCAH by genetic testing are mostly asymptomatic. Temporary female infertility and suboptimal cortisol response were commonly observed. Ongoing glucocorticoid therapy is not indicated in adults with CAH identified by family genotype studies unless symptomatic, but glucocorticoid stress coverage should be considered in select cases. Parents of a child with CAH have a 1:25 risk of having NCCAH; if the mother of a child with CAH has infertility, evaluation for NCCAH is indicated.