血清胰岛素样生长因子-1、硫酸脱氢表雄酮、抗苗勒管激素及骨形态发生蛋白6在快进展型青春期女童中的早期预警价值

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目的:研究血清胰岛素样生长因子-1(IGF-1)、硫酸脱氢表雄酮(DHEAS)、抗苗勒管激素(AMH)及骨形态发生蛋白6(BMP-6)水平对快进展型青春期(RPP)女童的早期预警价值。方法:回顾性分析2017年8月至2018年10月因乳房发育至苏州大学附属儿童医院内分泌遗传代谢科门诊就诊的750例女童的临床资料,随访6个月~1年,剔除失访、早期治疗、不满足各组入组标准的病例,将剩余的138例女童按照入组标准分为中枢性性早熟组(CPP)32例、RPP早期(EP-RPP)组33例、慢进展型青春期早期(EP-SPP)组32例及RPP组41例。同时选择同期苏州大学附属儿童医院健康体检、年龄为8~9岁的未发育女童33例作为健康对照组。检测各组的血清IGF-1、DHEAS、AMH及BMP-6水平,并比较各组一般资料、临床特点、实验室检查及影像学特点,应用SPSS 22.0软件进行统计学分析,绘制受试者工作特征曲线(ROC)判断血清IGF-1、DHEAS、AMH及BMP-6在预测RPP中的价值。结果:1.血清卵泡刺激素(FSH)峰值在EP-SPP组、EP-RPP组和RPP组分别为15.10(13.86~19.80) IU/L、11.99(9.18~16.16) IU/L、和11.43(9.37~15.63) IU/L;血清FSH/黄体生成素(LH)峰值比在EP-SPP组、EP-RPP组和RPP组分别为3.20(2.44~4.58)、1.86(1.05~3.16)和0.76(0.49~0.99);EP-SPP组血清FSH峰值、血清FSH/LH峰值比均高于EP-RPP组,差异均有统计学意义(n P0.05);2.血清IGF-1水平在健康对照组、EP-SPP组、EP-RPP组、CPP组和RPP组分别为166.00(126.50~188.00) μg/L、199.00(170.50~262.50) μg/L、252.00(233.00~291.50) μg/L、288.00(252.00~376.00) μg/L和382.00(264.00~499.50) μg/L;EP-SPP组、EP-RPP组、CPP组和RPP组的血清IGF-1水平均高于健康对照组,差异均有统计学意义(均n P0.05);5.血清IGF-1水平曲线下面积为0.765,Cut-off值为232.5 μg/L,该界值的特异度为83.30%,敏感度为75.00%;血清FSH峰值与血清FSH/LH峰值比联合曲线下面积为0.795。n 结论:血清FSH峰值与血清FSH/LH峰值比联合、血清IGF-1可作为早期预测早青春期女童青春期进展快慢的有效指标之一;血清DHEAS虽然不能作为预测RPP的早期预警指标,但是对青春期启动和进程的调控具有重要意义,其水平高低可能与Tanner分期有关。“,”Objective:To investigate the value of serum insulin-like growth factor-1 (IGF-1), dehydroepiandrosterone sulphate (DHEAS), anti-Müllerian hormone (AMH) and bone morphogenetic protein 6 (BMP-6) in prediction of rapidly progressive puberty(RPP) in girls.Methods:The data of 750 girls who visited the Department of Endocrinology, Metabolism and Genetic Disorders, Children′s Hospital of Soochow University from August 2017 to October 2018 because of breast development were retrospectively analyzed.After following up these girls for 6 months to 1 year, those who were lost to follow up, received early treatment and failed to meet the inclusion criteria were excluded.The remaining 138 girls were divided into the central precocious puberty group (CPP, 32 cases), the early puberty with RPP group (EP-RPP, 33 cases), the early puberty with slow progression puberty group (EP-SPP, 32 cases) and RPP group (41 cases) according to the inclusion criteria.The healthy control group consisted of 33 undeveloped girls aged 8 to 9 who underwent physical examination in the same hospital over the same period.The serum concentrations of IGF-1, DHEAS, AMH and BMP-6 were measured.The general information, clinical manifestations, laboratory examination results and radiological features were compared among different groups.Statistical analysis was performed by using SPSS 22.0, and the receiver operating characteristic curve (ROC) was drawn to investigate the value of IGF-1, DHEAS, AMH and BMP-6 in prediction of RPP.Results:(1)The serum follicle stimulating hormone(FSH) peak value was 15.10(13.86-19.80) IU/L in the EP-SPP group, 11.99(9.18-16.16) IU/L in the EP-RPP group and 11.43(9.37-15.63) IU/L in the RPP group.The ratio of serum FSH/luteinizing hormone(LH) peak values was 3.20(2.44-4.58) in the EP-SPP group, 1.86(1.05-3.16) in the EP-RPP group and 0.76(0.49-0.99) in the RPP group.The serum FSH peak value and the ratio of serum FSH/LH peak values in the EP-SPP group were significant higher than those in the EP-RPP group(all n P0.05). (2)The serum IGF-1 levels of the healthy control group, EP-SPP group, EP-RPP group, CPP group and RPP group were 166.00(126.50-188.00) μg/L, 199.00(170.50-262.50) μg/L, 252.00(233.00-291.50) μg/L, 288.00(252.00-376.00) μg/L and 382.00(264.0-499.50) μg/L, respectively.The serum IGF-1 levels of the EP-SPP group, EP-RPP group, CPP group and RPP group were all significantly higher than those in the healthy control group (alln P0.05). (5)The area under the ROC curve of serum IGF-1 levels was 0.765, the cut-off value was 232.5 μg/L, the specificity for the cut-off value was 83.30%, and the sensitivity was 75.00%.The combined area under the ROC curve of the serum FSH peak value and the ratio of serum FSH/LH peak values was 0.795.n Conclusions:Serum IGF-1 levels and the combination of the serum FSH peak value and the ratio of serum FSH/LH peak values can be used as effective indicators of slowly and rapidly progressive puberty in early adolescent girls.Serum DHEAS cannot be used as an early warning index of RPP, but it plays a critical role in the regulation of puberty initiation and process.Serum DHEAS levels may be related to the Tanner stage.
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