Multi-biomarker models based on the androgen backdoor pathway for diagnosing 17α-hydroxylase/17,20-lyase deficiency.

IF 3.3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Endocrine Pub Date : 2026-09-28 DOI:10.1007/s12020-026-04767-5

Yongqi Liu, Susu Cai, Tingting Zhang, Shixin Sun, Xujing Kong, Jianfeng Zhou, Baorong Chen, Zenghe Li

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引用次数: 0

Abstract

Objectives: 17α-hydroxylase/17,20-lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia (CAH) that is frequently underdiagnosed, particularly in partial deficiency. We evaluated androgen backdoor pathway steroids as diagnostic biomarkers for 17OHD.

Methods: We included 50 confirmed 17OHD patients and 266 healthy controls. Six androgen backdoor pathway steroids-5α-dihydroprogesterone (5α-DHP), 17OH-dihydroprogesterone (17OH-DHP), 17OH-allopregnanolone (17OH-Allo), androsterone (AN), androstanediol (3α-diol), and 5α-dihydrotestosterone (DHT)-were quantified in plasma using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Multi-marker models were constructed using single-marker area under the curve (AUC) thresholds ( > 0.7, > 0.8, and > 0.9) and subsequently evaluated in the validation cohort.

Results: In males, AUCs for 5α-DHP, 17OH-DHP, 17OH-Allo, AN, 3α-diol, and DHT were 1.000, 0.754, 0.531, 0.940, 0.859, and 0.954; in females, they were 0.999, 0.710, 0.546, 0.964, 0.809, and 0.929. Based on single-marker AUC thresholds, multi-marker diagnostic models were constructed: AUC > 0.7, (5α-DHP + 17OH-DHP) / (AN + 3α-diol + DHT) (cut-off > 0.865 in males, > 1.415 in females); AUC > 0.8, 5α-DHP / (AN + 3α-diol + DHT) (cut-off > 0.779 in males, > 1.402 in females); and AUC > 0.9, 5α-DHP / (AN + DHT) (cut-off > 1.053 in males, > 2.146 in females). All models achieved an AUC of 1.000 with 100% sensitivity and specificity and showed promising diagnostic performance in the validation cohort.

Conclusions: The combined models showed promising diagnostic performance for 17OHD and were preliminarily evaluated in the validation cohort, supporting the potential of androgen backdoor pathway steroids as diagnostic biomarkers for 17OHD.

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基于雄激素后门通路的多生物标志物模型诊断17α-羟化酶/17,20裂解酶缺乏症。

目的：17α-羟化酶/17,20裂解酶缺乏症（17OHD）是一种罕见的先天性肾上腺增生症（CAH），常被误诊，尤其是部分缺乏症。我们评估了雄激素后门通路类固醇作为17OHD的诊断生物标志物。方法：纳入50例确诊的17hd患者和266例健康对照。采用超高效液相色谱-串联质谱（UPLC-MS/MS）对血浆中5α-二氢孕酮（5α-DHP）、17oh -二氢孕酮（17OH-DHP）、17oh -异孕酮（17OH-Allo）、雄酮（AN）、雄甾二醇（3α-二醇）和5α-二氢睾酮（DHT） 6种雄激素后门途径类固醇进行定量分析。采用受试者工作特征（ROC）分析评估诊断效果。采用单标记曲线下面积（AUC）阈值（> 0.7、> 0.8和> 0.9）构建多标记模型，随后在验证队列中进行评估。结果：男性5α-DHP、17OH-DHP、17OH-Allo、AN、3α-diol、DHT的auc分别为1.000、0.754、0.531、0.940、0.859、0.954；女性分别为0.999、0.710、0.546、0.964、0.809和0.929。基于单标记AUC阈值，构建多标记AUC诊断模型：AUC > 0.7, (5α-DHP + 17OH-DHP) / (AN + 3α-二醇+ DHT)（截断值>男性为0.865，女性为1.415）；AUC > 0.8, 5α-DHP / (AN + 3α-diol + DHT)（临界值>男性为0.779，女性为1.402）；AUC > 0.9, 5α-DHP / (AN + DHT)（临界值：男性> 1.053，女性> 2.146）。所有模型的AUC均为1.000，灵敏度和特异性均为100%，在验证队列中显示出良好的诊断性能。结论：联合模型对17OHD具有良好的诊断性能，并在验证队列中进行了初步评估，支持雄激素后门通路类固醇作为17OHD诊断生物标志物的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Endocrine ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

5.40%

发文量

295

审稿时长

1.5 months

期刊介绍： Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology. Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted. Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.