ArticleEndocrine2026
Multi-biomarker models based on the androgen backdoor pathway for diagnosing 17α-hydroxylase/17,20-lyase deficiency.
Article in Endocrine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectives17α-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.
methodsWe 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.
resultsIn 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.
conclusionsThe 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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