Chesover Alexander D, Millar Heather, Sepiashvili Lusia, Adeli Khosrow, Palmert Mark R, Hamilton Jill
Division of Endocrinology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto M5G 1H4, Canada.
Section of Gynaecology, Division of Endocrinology, Department of Obstetrics and Gynaecology, The Hospital for Sick Children, University of Toronto M5G 1H4, Toronto, Canada.
J Endocr Soc. 2019 Dec 18;4(2):bvz030. doi: 10.1210/jendso/bvz030. eCollection 2020 Feb 1.
Screening for and diagnosing non classic congenital adrenal hyperplasia (NCCAH) uses serum 17-hydroxyprogesterone (17OHP) thresholds established from immunoassay data; however, a new liquid-chromatography tandem mass spectrometry (LC-MS/MS) method results in lower 17OHP values. The evolution of immunoassays is also challenging our diagnostic cut-off for glucocorticoid insufficiency and few data re-evaluate the utility of testing for glucocorticoid insufficiency in NCCAH.
(1) Evaluate the 17OHP threshold that predicts NCCAH in children using LC-MS/MS, and (2) determine the prevalence of glucocorticoid insufficiency in NCCAH.
A retrospective chart review of pediatric patients who underwent ACTH stimulation tests with cortisol and 17OHP measurements from 2011 to 2018 for assessment of NCCAH. Other adrenal pathologies were excluded. A cortisol < 415 nmol/L defined glucocorticoid insufficiency. Published correlation data determined a 17OHP of 3.3 nmol/L by LC-MS/MS was equivalent to 6 nmol/L by immunoassay. Data analysis was by measures of diagnostic accuracy.
Of 188 patients included, 23 (12%) had NCCAH (21/23 had genetic confirmation); the remaining 2 had peak 17OHP 30 nmol/L. Baseline 17OHP 6 nmol/L most accurately screened for NCCAH-sensitivity and specificity 96%. Almost all genetically confirmed NCCAH (20/21) had peak 17OHP > 30 nmol/L; all subjects with other diagnoses peaked < 30 nmol/L. Glucocorticoid insufficiency was present in 55% with NCCAH.
Despite the increased specificity of LC-MS/MS, a baseline 17OHP 6 nmol/L most accurately screened for NCCAH; this supports current practice guidelines. This threshold identified all with glucocorticoid insufficiency, notably prevalent in our cohort and for whom glucocorticoid stress dosing should be considered.
非经典型先天性肾上腺皮质增生症（NCCAH）的筛查和诊断采用基于免疫分析数据确定的血清17-羟孕酮（17OHP）阈值；然而，一种新的液相色谱串联质谱法（LC-MS/MS）得出的17OHP值更低。免疫分析方法的演变也对我们糖皮质激素缺乏症的诊断临界值提出了挑战，而且几乎没有数据重新评估NCCAH中糖皮质激素缺乏症检测的效用。
（1）使用LC-MS/MS评估预测儿童NCCAH的17OHP阈值，（2）确定NCCAH中糖皮质激素缺乏症的患病率。
对2011年至2018年期间接受促肾上腺皮质激素刺激试验并测量皮质醇和17OHP以评估NCCAH的儿科患者进行回顾性病历审查。排除其他肾上腺疾病。皮质醇<415 nmol/L定义为糖皮质激素缺乏。已发表的相关性数据确定，LC-MS/MS检测的17OHP为3.3 nmol/L相当于免疫分析检测的6 nmol/L。数据分析采用诊断准确性测量方法。
纳入的188例患者中，23例（12%）患有NCCAH（21/23例有基因确诊）；其余2例17OHP峰值>30 nmol/L。基线17OHP>6 nmol/L对NCCAH的筛查最为准确，敏感性和特异性为96%。几乎所有基因确诊的NCCAH（20/21）的17OHP峰值>30 nmol/L；所有其他诊断的受试者峰值<30 nmol/L。55%的NCCAH患者存在糖皮质激素缺乏。
尽管LC-MS/MS的特异性有所提高，但基线17OHP>6 nmol/L对NCCAH的筛查最为准确；这支持了当前的实践指南。该阈值识别出所有糖皮质激素缺乏的患者，在我们的队列中尤为普遍，对此应考虑给予糖皮质激素应激剂量。
