Objective

To define liquid chromatography tandem mass spectrometry (LC-MS/MS)–based cutoff levels and panels of steroid hormones, to improve diagnosis of nonclassic congenital adrenal hyperplasia (NCCAH) and other partial enzyme defects in the adrenals.

Design

Prospective cohort analysis.

Setting

University hospital-based tertiary endocrine center.

Patients

One hundred and twenty-one healthy adults and 65 patients evaluated for possible NCCAH (validation cohort).

Interventions

The LC-MS/MS–determined cutoffs for 11 steroids (basal and cosyntropin-stimulated) were defined by 2.5% and 97.5% percentile in healthy subjects. Validation cohort was used for comparison.

Main Outcome Measures

Percentage of patients diagnosed with NCCAH among patients with polycystic ovary syndrome (PCOS)-like symptomatology. Evaluation of the defined LC-MS/MS–based cutoff levels for steroid hormones among this patient group.

Results

Of the 65 PCOS-like patients evaluated for possible NCCAH, 8 (12.5%) were discovered and genetically verified, and 2 had classic congenital adrenal hyperplasia. Cosyntropin-stimulated 17-hydroxyprogesterone (17OHP) showed the best diagnostic accuracy for NCCAH with an area under the curve of 0.95 (0.89–1.0 with a sensitivity of 86% and a specificity of 88%. In homozygote patients, 21-deoxycortisol and 17OHP levels were elevated, in heterozygote patients only 17OHP (basal or stimulated) was raised. Four healthy patients in the validation cohort had 17OHP above the basal cutoff.

Conclusions

The NCCAH syndrome is frequent in patients with suspected PCOS, and should be considered as a routine screening when assessing infertility. We suggest the use of serum steroid profiling, including 21-deoxycortisol, together with the cosyntropin stimulation test with 17OHP. Our data support a 17OHP cutoff of 8.5 nmol/L (2.8 ng/mL) 60 minutes after cosyntropin stimulation, when measured with LC-MS/MS, significantly lower than current European guidelines.

Clinical trials Number

NCT0218660.

中文翻译：

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肾上腺类固醇分析作为区分多囊卵巢综合征与非经典先天性肾上腺增生症的诊断工具：使用液相色谱串联质谱法确定简单的筛查可能性和正常截止水平

客观的

定义基于液相色谱串联质谱法 (LC-MS/MS) 的截止水平和类固醇激素组，以改进非经典先天性肾上腺增生 (NCCAH) 和肾上腺其他部分酶缺陷的诊断。

设计

前瞻性队列分析。

环境

以大学医院为基础的三级内分泌中心。

患者

121 名健康成人和 65 名患者评估了可能的 NCCAH（验证队列）。

干预措施

LC-MS/MS 确定的 11 种类固醇（基础和辅酶促激素）的截止值在健康受试者中定义为 2.5% 和 97.5%。验证队列用于比较。

主要观察指标

多囊卵巢综合征 (PCOS) 样症状患者中诊断为 NCCAH 的患者百分比。评估该患者组中基于 LC-MS/MS 的类固醇激素的定义截止水平。

结果

在评估可能的 NCCAH 的 65 名 PCOS 样患者中，8 名 (12.5%) 被发现并经过基因验证，2 名患有典型的先天性肾上腺增生症。Cosyntropin 刺激的 17-羟孕酮 (17OHP) 显示出 NCCAH 的最佳诊断准确性，曲线下面积为 0.95 (0.89–1.0，灵敏度为 86%，特异性为 88%)。在纯合子患者中，21-脱氧皮质醇和 17OHP水平升高，在杂合子患者中仅 17OHP（基础或刺激）升高。验证队列中的四名健康患者的 17OHP 高于基础截止值。

结论

NCCAH 综合征在疑似 PCOS 患者中很常见，在评估不孕症时应将其视为常规筛查。我们建议使用血清类固醇分析，包括 21-脱氧皮质醇，以及 17OHP 的促肾上腺素刺激试验。我们的数据支持 17OHP 截止值为 8.5 nmol/L (2.8 ng/mL)，在使用 LC-MS/MS 测量时，促肾上腺素刺激后 60 分钟明显低于当前的欧洲指南。

临床试验编号

NCT0218660。