Ben Said Wogud, Lempesis Ioannis G, Fernandez-Garcia Silvia, Thangaratinam Shakila, Arlt Wiebke, Idkowiak Jan
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, University of Birmingham, Birmingham, B15 2TT, United Kingdom.
Department of Endocrinology and Diabetes, Birmingham Children's Hospital, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, B4 6NH, United Kingdom.
Eur J Endocrinol. 2025 Aug 29;193(3):S1-S14. doi: 10.1093/ejendo/lvaf167.
Premature adrenarche (PA), characterised by pre-pubertal adrenal androgen excess and hyperandrogenic symptoms, is considered a forerunner of polycystic ovary syndrome, which comes with increased metabolic risk. Here, we aimed to systematically evaluate the evidence on surrogate parameters of metabolic risk in children with PA.
We searched major databases (1990-March 2025) for studies on PA in children analysing body composition and markers of glucose and lipid metabolism. Two reviewers independently selected studies, collected data, and appraised study quality. Results were standardised, tabulated, and pooled for meta-analysis.
Twenty-five case-control studies reported on 694 children with PA and 567 healthy controls (boys and girls). Height standard deviation score (SDS), weight SDS, and body mass index SDS were significantly higher in PA than in controls. Children with PA also presented with higher fasting insulin (FI) levels than controls (MD: 15.04, 95% CI: 5.27-24.81 pmol/L; I2 = 91%). These findings persisted after sensitivity analysis for gender and risk of bias assessment. Other markers of metabolic risk, such as fasting glucose, HOMA-IR, mean serum glucose and insulin during the oral glucose tolerance test, and fasting lipids, did not differ between children with PA and controls.
Children with PA are taller, heavier, and have higher FI levels than their healthy peers at presentation. We observed significant heterogeneity of reported outcomes with generally small participant numbers in the included studies. Large-scale studies with comprehensive, unified assessment and long-term follow-up are needed to explore the extent of metabolic dysfunction that may develop over time.
早熟肾上腺初现（PA）的特征是青春期前肾上腺雄激素过多和高雄激素症状，被认为是多囊卵巢综合征的先兆，多囊卵巢综合征会增加代谢风险。在此，我们旨在系统评估PA患儿代谢风险替代参数的证据。
我们检索了主要数据库（1990年至2025年3月）中关于分析PA患儿身体成分以及葡萄糖和脂质代谢标志物的研究。两名评审员独立选择研究、收集数据并评估研究质量。对结果进行标准化、制表并汇总以进行荟萃分析。
25项病例对照研究报告了694例PA患儿和567例健康对照（男童和女童）的情况。PA患儿的身高标准差评分（SDS）、体重SDS和体重指数SDS显著高于对照组。PA患儿的空腹胰岛素（FI）水平也高于对照组（MD：15.04，95%CI：5.27 - 24.81 pmol/L；I2 = 91%）。在对性别和偏倚风险评估进行敏感性分析后，这些结果仍然存在。其他代谢风险标志物，如空腹血糖、HOMA-IR、口服葡萄糖耐量试验期间的平均血清葡萄糖和胰岛素以及空腹血脂，在PA患儿和对照组之间没有差异。
PA患儿在就诊时比健康同龄人更高、更重且FI水平更高。我们观察到所报告结果存在显著异质性，纳入研究中的参与者数量普遍较少。需要进行大规模研究，进行全面、统一的评估并进行长期随访，以探索随着时间推移可能出现的代谢功能障碍程度。
