Characteristics of androgen metabolic pathways in patients with 21-hydroxylase deficiency and their association with disease control status

Objective: 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. Methods: 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. Results: 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 = 11.90, 95%CI:1.43-98.79, P = 0.02). 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 = 0.02), 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