Steroids Laboratory, Adrenal and Hypertension Unit, Division of Endocrinology and Metabolism, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil.
Clin Endocrinol (Oxf). 2010 Dec;73(6):700-6. doi: 10.1111/j.1365-2265.2010.03871.x.
Congenital adrenal hyperplasia caused by classic 21-hydroxylase deficiency (21OHD) is an autosomal recessive disorder with a high prevalence of asymptomatic heterozygote carriers (HTZ) in the general population, making case detection desirable by routine methodology. HTZ for classic and nonclassic (NC) forms have basal and ACTH-stimulated values of 17-hydroxyprogesterone (17OHP) that fail to discriminate them from the general population. 21-Deoxycortisol (21DF), an 11-hydroxylated derivative of 17OHP, is an alternative approach to identify 21OHD HTZ.
To determine the discriminating value of basal and ACTH-stimulated serum levels of 21DF in comparison with 17OHP in a population of HTZ for 21OHD (n = 60), as well as in NC patients (n = 16) and in genotypically normal control subjects (CS, n = 30), using fourth generation tandem mass spectrometry after HPLC separation (LC-MS/MS).
Basal 21DF levels were not different between HTZ and CS, but stimulated values were increased in the former and virtually nonresponsive in CS. Only 17·7% of the ACTH-stimulated 21DF levels overlapped with CS, when compared to 46·8% for 17OHP. For 100% specificity, the sensitivities achieved for ACTH-stimulated 21DF, 17OHP and the quotient [(21DF + 17OHP)/F] were 82·3%, 53·2% and 87%, using cut-offs of 40, 300 ng/dl and 46 (unitless), respectively. Similar to 17OHP, ACTH-stimulated 21DF levels did not overlap between HTZ and NC patients. A positive and highly significant correlation (r = 0·846; P < 0·001) was observed between 21DF and 17OHP pairs of values from NC and HTZ.
This study confirms the superiority of ACTH-stimulated 21DF, when compared to 17OHP, both measured by LC-MS/MS, in identifying carriers for 21OHD. Serum 21DF is a useful tool in genetic counselling to screen carriers among relatives in families with affected subjects, giving support to molecular results.
经典 21-羟化酶缺乏症（21OHD）引起的先天性肾上腺增生是一种常染色体隐性遗传病，在普通人群中无症状的杂合子携带者（HTZ）的患病率很高，因此希望通过常规方法进行病例检测。经典和非经典（NC）形式的 HTZ 的基础和 ACTH 刺激 17-羟孕酮（17OHP）值未能将其与普通人群区分开来。21-脱氧皮质醇（21DF）是 17OHP 的 11-羟化衍生物，是一种替代方法，可用于鉴定 21OHD HTZ。
使用 HPLC 分离后的第四代串联质谱（LC-MS/MS），确定基础和 ACTH 刺激的血清 21DF 水平与 17OHP 相比，在 21OHD（n = 60）的 HTZ 人群、NC 患者（n = 16）和基因正常对照（CS，n = 30）中的鉴别价值。
HTZ 和 CS 之间的基础 21DF 水平没有差异，但前者的刺激值升高，而 CS 则几乎没有反应。与 46.8%的 17OHP 相比，只有 17.7%的 ACTH 刺激 21DF 水平与 CS 重叠。对于 100%的特异性，对于 ACTH 刺激的 21DF、17OHP 和商[(21DF + 17OHP)/F]，当使用 40、300ng/dl 和 46（无单位）的截止值时，获得的灵敏度分别为 82.3%、53.2%和 87%。与 17OHP 相似，HTZ 和 NC 患者之间的 ACTH 刺激的 21DF 水平没有重叠。观察到 NC 和 HTZ 患者的 21DF 和 17OHP 值对之间存在正相关（r = 0.846；P < 0.001）。
本研究证实，与通过 LC-MS/MS 测量的 17OHP 相比，ACTH 刺激的 21DF 在识别 21OHD 携带者方面具有优越性。血清 21DF 是遗传咨询中筛选受影响个体亲属携带者的有用工具，支持分子结果。
