摘要
背景 中枢性性早熟(CPP)是儿童内分泌常见疾病,近年来呈逐年增加趋势,依据青春期发育进程可分为快进展型中枢性性早熟(RP-CPP)和缓慢进展型中枢性性早熟(SP-CPP)。RP-CPP具有极大危害,其与SPCPP在早期临床鉴别中存在困难,主要依靠随访中青春期发育进程及骨龄进展情况进行判断,目前缺乏有效的实验室检查指标来预测RP-CPP。目的 探讨促黄体生成素(LH)/促卵泡生成素(FSH)比值对RP-CPP的预测价值。方法回顾性选取2020年1月—2022年5月郑州大学附属儿童医院收治的4~10岁CPP女童(n=380),依据青春期发育进程等指标分为RP-CPP组(n=130)及SP-CPP组(n=250),对两组间的临床特征进行对比分析,进行RP-CPP影响因素的单因素和多因素Logistic回归分析,并绘制LH/FSH比值对RP-CPP预测价值的受试者工作特征(ROC)曲线。结果 RP-CPP组女童的身高、体质量、BMI、胰岛素样生长因子1(IGF-1)、骨龄与实际年龄差值、双侧卵巢体积、LH基础值、雌二醇水平、LH基础值/FSH基础值、LH峰值/FSH峰值均高于SP-CPP组(P<0.05)。多因素Logistic回归分析,结果显示,LH基础值(OR=0.882,95%CI=0.686~0.986,P=0.035)及LH峰值/FSH峰值(OR=0.492,95%CI=0.336~0.723,P<0.001)是CPP患者进展为RP-CPP的影响因素。LH基础值/FSH基础值、LH峰值/FSH峰值均与身高、IGF-1、LH基础值、雌二醇水平、LH峰值、卵巢容积及骨龄呈正相关(P<0.05)。ROC曲线显示LH基础值/FSH基础值、LH峰值/FSH峰值较其他指标对RP-CPP的预测价值更高,LH基础值/FSH基础值为0.63时,约登指数最大为0.258[灵敏度为43.1%,特异度为82.7%,ROC曲线下面积(AUC)=0.644],LH峰值/FSH峰值为1.39时,约登指数最大为0.276(灵敏度为74.6%,特异度53.0%,AUC=0.655),二者联合的预测模型优于单一指标预测模型(AUC=0.668)。对未进行临床干预患儿随访6个月后的基础促性腺激素水平进行分析,随访6个月后RP-CPP组的身高增长、ΔLH、ΔFSH、骨龄增长及卵巢容积增长均多于SP-CPP组(P<0.05)。结论 LH基础值/FSH基础值及LH峰值/FSH峰值是RP-CPP的早期预测指标,当LH/FSH基础值≥0.63或LH峰值/FSH峰值≥1.39时,需考虑RP-CPP的可能性,并且二者联合的预测价值优于单一指标,可作为临床应用促性腺激素释放激素类似物治疗的辅助参考指标。
Background Central precocious puberty(CPP)is a common endocrine disease in children,which shows an increasing trend year by year in recent years.It can be divided into fast-progressing central precocious puberty(RP-CPP)and slow-progressing central precocious puberty(SP-CPP)through pubertal development.RP-CPP has great harm,but it is difficult to distinguish it from SP-CPP in early clinical stage,mainly relying on the progress of adolescent development and bone age during follow-up.At present,there is a lack of effective laboratory indicators to predict RP-CPP.Objective To investigate the relationship between luteinizing hormone(LH)/follicle-stimulating hormone(FSH)ratio and pubertal development.Methods CPP girls aged 4-10 years old(n=380)admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2020 to May 2022 were regression selected and divided into RP-CPP group(n=130)and SP-CPP group(n=250 cases)according to indicators such as puberal development process.Clinical characteristics of the two groups were compared and analyzed.Univariate and multivariate Logistic regression analysis of the influencing factors of RP-CPP was performed,and ROC curve of LH/FSH ratio on the predictive value of RP-CPP was drawn.Results The height,weight,BMI,IGF-1,difference between bone age and actual age,bilateral ovarian volume,LH base value,estradiol level,LH base value/FSH base value,and LH peak/FSH peak value of girls in RP-CPP group were all higher than those in SP-CPP group,with statistical significance(P<0.05).Regression analysis showed that CPP patients progressed to RP-CPP related serological indexes when LH base value and LH peak/FSH peak were detected.LH base/FSH base value and LH peak/FSH peak were positively correlated with height,IGF-1,LH base value,estradiol level,LH peak,ovarian volume and bone age(P<0.05).ROC curve showed that the LH base/FSH base value and LH peak/FSH peak value were more sensitive and specific than other indexes to the predictive value of RP-CPP.When the LH base/FSH base value was 0.63,the Yoden index reached a maximum of 0.258(sensitivity 43.1%,specificity 82.7%,AUC=0.644).When the LH peak/FSH peak was 1.39,the maximum Jorden index was 0.276(sensitivity 74.6%,specificity 53.0%,AUC=0.655).The combined prediction model is better than the single index prediction model(AUC=0.668).The basal gonadotropin levels of children without clinical intervention were analyzed after 6 months of follow-up.It was found that the height increase,ΔLH,ΔFSH,bone age increase and ovarian volume increase in RP-CPP group were significantly higher than those in SP-CPP group after 6 months of follow-up,and the difference was statistically significant(P<0.05).Conclusion LH base/FSH base value and LH peak/FSH peak are early predictors of RP-CPP.When LH/FSH base value≥0.63 or LH peak/FSH peak≥1.39,the possibility of RP-CPP should be considered,and the combined predictive value of the two indicators is better than that of a single indicator.It can be used as an auxiliary reference index for clinical application of gonadotropin-releasing hormone analogue therapy.
作者
袁淑娴
林一凡
赵艺璇
魏怡
鲁帅
卫海燕
YUAN Shuxian;LIN Yifan;ZHAO Yixuan;WEI Yi;LU Shuai;WEI Haiyan(Department of Endocrinology and Metabolism,Children's Hospital Affiliated to Zhengzhou University,Zhengzhou 450018,China)
出处
《中国全科医学》
CAS
北大核心
2025年第3期352-357,共6页
Chinese General Practice
基金
河南省科技局项目(212102310438,232102310088)
国家重点研发计划(2021YFC2701900)。
关键词
中枢性性早熟
促卵泡激素
黄体生成素
青春期发育
女童
病例对照研究
Central precocious puberty
Follicle-stimulating hormone
Luteinizing hormone
Adolescent development
Girls
Case-control study
