{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T14:30:05Z","timestamp":1788877805362,"version":"build-2803163510"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the activity characteristics of distinct androgen metabolic pathways in patients with 21-hydroxylase deficiency (21OHD) and their correlation with disease control status, and to elucidate the metabolic pathway features and underlying mechanisms in poorly controlled patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 111 patients with confirmed 21OHD were enrolled in this study. Clinical data and steroid hormone profiles were collected, and robust standardized Z-scores were calculated for each steroid hormone. K-means clustering analysis was performed using the robust standardized Z-scores of 7 signature steroid hormones to stratify patients into a well-controlled group and a poorly controlled group. Differences in clinical characteristics, pathway activities and key enzyme conversion efficiencies were compared between and within the two groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>K-means clustering analysis classified 102 patients into the well-controlled group and 9 into the poorly controlled group. Multivariate analysis identified puberty as an independent risk factor for poor disease control (OR\u00a0=\u00a011.90, 95%CI:1.43\u201398.79, P\u00a0=\u00a00.02). Among pubertal patients, the poorly controlled group had a significantly higher relative weight of classical pathway androgen load than the well-controlled group (63.92% vs. 46.19%, P\u00a0=\u00a00.02), and the proportion of the classical pathway in the poorly controlled group was markedly higher than that of the 11-oxygenated and backdoor pathways (both P&amp;lt;0.05). Additionally, the conversion efficiency of the 21-deoxycortisol (21DOF) pathway was significantly decreased in the poorly controlled group (P\u00a0=\u00a00.004), suggesting relatively restricted CYP11B1 activity which drives the shift of androgen metabolism toward the classical pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In poorly controlled pubertal patients with 21OHD, the relative insufficiency of CYP11B1 activity and the dysregulation of the metabolic network jointly lead to the shift of androgen synthesis to the classical pathway, forming a \u201cclassical pathway dominance\u201d. This finding deepens the understanding of the pathological mechanism of 21OHD from the perspective of pathway dynamics and provides a novel theoretical basis for individualized clinical treatment of the disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1762815","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T04:27:10Z","timestamp":1778473630000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Characteristics of androgen metabolic pathways in patients with 21-hydroxylase deficiency and their association with disease control status"],"prefix":"10.3389","volume":"17","author":[{"given":"Hemeng","family":"Chong","sequence":"first","affiliation":[{"name":"Department of Pediatrics, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalei","family":"Pi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Second Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, 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