Division of Pediatric Endocrinology, Department of Pediatrics, Technische Universität München, München, Germany.
Horm Res Paediatr. 2011;75(4):264-8. doi: 10.1159/000322580. Epub 2010 Dec 22.
Mild forms of simple virilizing congenital adrenal hyperplasia (CAH) may be missed in newborn screening. In the pre-newborn-screening era, missed diagnosis of simple virilizing CAH was not infrequent in boys. Elevated adrenal androgens lead to accelerated growth and bone maturation. Traditional treatment of CAH consists of the suppression of ACTH through glucocorticoid replacement, in an attempt to reduce excessive androgen production.
To retrospectively analyze early growth pattern and bone maturation in untreated boys with simple virilizing CAH.
In the pre-newborn screening era, 13 boys had a late diagnosis of simple virilizing classical CAH. Diagnosis of 21-hydroxylase deficiency was confirmed by mutation analysis of the CYP21A2 gene in all patients. Growth data were retrospectively collected from standarized preventive medical checkups at the regular pediatrician until the time of diagnosis of CAH.
Length was 0.1 ± 0.8 SDS (mean ± SD) at birth, 0.2 ± 1 SDS at 3 months, 0.2 ± 0.9 SDS at 6 months, 0.7 ± 1 SDS at 1 year, +1.1 ± 0.9 SDS at 2 years and +1.8 ± 1.2 SDS at 4 years. At diagnosis, mean chronological age was 4.4 ± 1.6 years and height SDS was 2 ± 1.7. Bone age was accelerated (9.4 ± 4 years) at diagnosis. Signs that had led to diagnosis were pubic hair (n = 11), accelerated growth rate (n = 6) and birth of an affected sister (n = 3). Despite late start of hydrocortisone treatment, mean final height was -1 ± 0.9 SDS. Seven of 18 patients had a final height within 1 SD of target height.
Height velocity is not markedly increased in untreated boys with simple virilizing CAH in the first 6 months of life, indicating that infants are relatively androgen insensitive during that period. After the first 6 months of life, growth velocity increases significantly and elevated androgens lead to advanced skeletal maturation. This observation has implications for lower hydrocortisone doses to be used in CAH children during the first 6 months of life. In addition, staying alert for clinical symptoms and signs of simple virilizing CAH is still warranted, since mild forms may be missed in newborn screening.
轻度单纯男性化型先天性肾上腺皮质增生症（CAH）在新生儿筛查中可能被漏诊。在新生儿筛查前时代，男孩中单纯男性化型 CAH 的漏诊并不罕见。升高的肾上腺雄激素会导致生长加速和骨成熟加速。CAH 的传统治疗方法是通过糖皮质激素替代来抑制 ACTH，以试图减少过多雄激素的产生。
回顾性分析未经治疗的单纯男性化型 CAH 男孩的早期生长模式和骨成熟情况。
在新生儿筛查前时代，13 名男孩被确诊为迟发性单纯男性化经典 CAH。所有患者均通过 CYP21A2 基因突变分析确诊 21-羟化酶缺乏症。生长数据是从标准化预防医学检查中回顾性收集的，这些检查是在定期儿科医生处进行的，直到 CAH 的诊断时间。
出生时长度为 0.1 ± 0.8 SDS（平均值 ± 标准差），3 个月时为 0.2 ± 1 SDS，6 个月时为 0.2 ± 0.9 SDS，1 岁时为 0.7 ± 1 SDS，2 岁时为 +1.1 ± 0.9 SDS，4 岁时为 +1.8 ± 1.2 SDS。诊断时，平均实际年龄为 4.4 ± 1.6 岁，身高 SDS 为 2 ± 1.7。骨龄加速（9.4 ± 4 岁）。导致诊断的迹象有阴毛（n = 11）、生长速度加快（n = 6）和患有受影响姐妹（n = 3）。尽管开始使用氢可的松治疗较晚，但平均最终身高为-1 ± 0.9 SDS。18 例患者中有 7 例最终身高在靶身高的 1 SD 范围内。
在生命的前 6 个月，未经治疗的单纯男性化型 CAH 男孩的身高增长速度并不明显增加，这表明在此期间婴儿相对雄激素不敏感。6 个月后，生长速度显著增加，升高的雄激素导致骨骼成熟加速。这一观察结果提示在 CAH 儿童生命的前 6 个月使用较低剂量的氢可的松。此外，仍然需要警惕单纯男性化型 CAH 的临床症状和体征，因为新生儿筛查可能会漏诊轻度病例。
