Wang Shan, Liu A Na, Liang Xin-Yi, Jiang Ling, Wu Wei, Dong Guan-Ping, Jiang Pei-Fang, Ni Yan, Fu Jun-Fen
Department of Endocrinology, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
Department of Neurology, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
World J Pediatr. 2025 Jul 24. doi: 10.1007/s12519-025-00937-z.
The diagnosis of central precocious puberty (CPP) relies on a gonadotropin releasing hormone stimulation test to assess the activation of the hypothalamic-pituitary-gonadal axis; this is costly and painful. Bile acids (BAs) have emerged as pivotal signaling molecules in the reproductive system. This study aimed to identify circulating BA profile signatures and explored if they may serve as biomarkers for CPP diagnosis in girls.
We enrolled 431 girls, including 241 in the training cohort and 190 in the validation cohort. Participants were divided into four groups based on their body mass index Z-score and whether they were diagnosed with CPP. Ultra-performance liquid chromatography coupled with tandem mass spectrometry was performed to quantify 38 serum BAs.
There were 18 individual BAs that were statistically different between CPP and non-CPP counterparts. The majority of these BAs (14/18) correlated significantly with sex-related hormones (P < 0.05). In girls with normal weight (NW), a logistic regression model combining chenodeoxycholic acid, tauroα-muricholic acid, and 6-ketolithocholic acid achieved an area under the receiver operating characteristic curve (AUC) of 0.885. For girls who were overweight/obese (OB), hyocholic acid and taurohyocholic acid enhanced the diagnostic efficiency of basal luteinizing and follicle stimulating hormones to an AUC value 0.914. In validation cohort, 75.34% NW girls and 84.09% OB girls were accurately classified.
Serum BA profiles of CPP girls showed significant changes that were associated with serum sex-related hormone levels. BA profiles could be potential biomarkers in CPP diagnosis and screening.
中枢性性早熟（CPP）的诊断依赖于促性腺激素释放激素刺激试验来评估下丘脑 - 垂体 - 性腺轴的激活；该方法成本高且会给患儿带来痛苦。胆汁酸（BAs）已成为生殖系统中的关键信号分子。本研究旨在确定循环胆汁酸谱特征，并探讨其是否可作为女童CPP诊断的生物标志物。
我们纳入了431名女童，其中241名在训练队列，190名在验证队列。根据她们的体重指数Z评分以及是否被诊断为CPP将参与者分为四组。采用超高效液相色谱 - 串联质谱法对38种血清胆汁酸进行定量分析。
18种个体胆汁酸在CPP组和非CPP组之间存在统计学差异。这些胆汁酸中的大多数（14/18）与性激素显著相关（P < 0.05）。在体重正常（NW）的女童中，结合鹅去氧胆酸、牛磺α - 鼠胆酸和6 - 酮石胆酸的逻辑回归模型在受试者工作特征曲线下面积（AUC）为0.885。对于超重/肥胖（OB）女童，猪胆酸和牛磺猪胆酸将基础促黄体生成素和促卵泡生成素的诊断效率提高到AUC值0.914。在验证队列中，75.34%的NW女童和84.09%的OB女童被准确分类。
CPP女童的血清胆汁酸谱显示出与血清性激素水平相关的显著变化。胆汁酸谱可能是CPP诊断和筛查的潜在生物标志物。
