Efficacy of morning serum LH combined with IGF-1 on pubertal initiation in children
-
摘要:
目的 探索晨血促黄体生成素(LH)和胰岛素样生长因子(IGF-1)水平对青春期启动的筛查切值点及筛查效能, 为合理开展GnRH刺激试验、促进儿童青春期系统管理提供依据。 方法 采用回顾调查的方法, 选取2019年1月1日至2021年12月31日在武汉儿童医院儿童保健科体检、乳房发育在B2~B3期或睾丸体积在4.00~10.00 mL、同期在内分泌病房进行GnRH刺激试验的1 724名8~13岁儿童为研究对象。采用彩色多普勒超声测定性腺容积, 采用GnRH刺激试验判断儿童青春期启动状况, 采用ROC曲线确定晨血LH、IGF-1筛查切值点, 并进行信度和效度检验。 结果 男童睾丸容积(4.88±2.19) mL, 性腺启动者检出率75.5%;女童卵巢容积(1.78±0.65) mL, 性腺启动者检出率91.39%。GnRH刺激试验显示, 男、女童LH峰值中位数为13.22, 21.79 IU/L, LH/FSH峰值比中位数为2.13, 1.87, 青春期启动者597, 864例。男、女童晨血LH对青春期启动的筛查切值点为0.23(Kappa=0.60)和0.22 IU/L (Kappa=0.66), IGF-1切值点为187.00(Kappa=0.45)和178.00 IU/L (Kappa=0.46)。男童晨血LH单项筛查、女童晨血LH与IGF-1串联筛查的灵敏度和特异度均较高, 筛查效能较好(Kappa指数分别为0.60, 0.64)。 结论 晨血LH、IGF-1是儿童青春期启动的良好预测指标, 当男童晨血LH达0.23 IU/L、女童晨血LH达0.22 IU/L且IGF-1达178.00 IU/L时, 应进行GnRH刺激试验明确青春期启动状况。 Abstract:Objective To explore the screening cut-off point and screening efficacy of morning serum LH combined with IGF-1 levels on puberty initiation to provide the basis for developing the gnrh stimulation test reasonably and promoting the systematic management of children and adolescence. Methods A retrospective study was conducted to select 1 724 children aged 8-13 years who took physical examination and were identified of breast development (between grade 2 and grade 3) or increased testicular volume (4.00-10.00 mL) in Child Health Department of Wuhan Children's Hospital during January 1st 2019 and December 31th 2021, and gonadotropin releasing hormone (GnRH) stimulation test was performed in endocrinology department ward in the same period.Doppler ultrasound was used to determine gonadal volume, and GnRH stimulation test was conducted to determine the puberty initiation in children.The ROC curve was utilized to determine the screening cut-off points of morning serum LH and IGF-1 on puberty initiation, and the reliability and validity of the cut-off points were all tested. Results The testicular volume was (4.88±2.19) mL in boys, and 75.5% was classified as initiation of gonadal growth.Whereas the ovaries volume was (1.78±0.65) mL in girls, and 91.39% classified as initiation of gonadal growth.The results of the GnRH stimulation test showed that among boys and girls, the medians LH peak were 13.22 and 21.79 IU/L, and the median LH/FSH peak ratios were 2.13 and 1.87.As a result, 597 boys and 864 girls were diagnosed as puberty initiation.Screening efficacy analysis indicated that the cut-off point of morning serum LH on puberty initiation were 0.23 IU/L in male (Kappa=0.60) and 0.22 IU/L in female (Kappa=0.66), and IGF-1 cut-off point were 187.00 IU/L in male (Kappa=0.45) and 178.00 IU/L in female (Kappa=0.46).High sensitivity and specificity and better screening efficacy (Kappa=0.60, 0.64) on single-item screening of morning blood LH in boys and tandem screening of LH and IGF-1 in girls. Conclusion Morning serum LH and IGF-1 are good predictors on puberty initiation.GnRH stimulation test should be carried out to determine the puberty initiation when morning serum LH reaches 0.23 IU/L in boys, morning serum LH reaches 0.22 IU/L and IGF-1 reaches 178.00 IU/L in girls. -
Key words:
- Blood /
- Luteinizing kormone /
- Insulin-like growth factor 1 /
- Puberty /
- Growth and development /
- Child
1) 利益冲突声明 所有作者声明无利益冲突。 -
表 1 不同年龄段儿童的性腺发育情况比较(x ±s)
Table 1. Gonadal development status in children of different ages(x ±s)
年龄/岁 男童 女童 人数 睾丸长径/cm 睾丸容积/mL 人数 最大卵泡直径/cm 卵巢容积/mL 8 378 0.47±0.15 1.58±0.63 9 122 2.52±0.32 3.94±1.67 383 0.51±0.16 1.82±0.62 10 186 2.60±0.43 4.37±2.32 184 0.53±0.17 1.96±0.67 11 222 2.77±0.36 5.16±2.10 61 0.57±0.19 2.15±0.56 12 129 2.90±0.37 5.85±2.03 16 0.67±0.30 2.20±0.67 13~13.7 43 2.89±0.53 5.39±2.30 合计 702 2.71±0.41 4.88±2.19 1 022 0.50±0.16 1.78±0.65 F值 22.34 17.42 11.67 20.90 注:P值均 < 0.01。 表 2 不同性别年龄段儿童GnRH刺激试验及IGF-1值比较[M(P25,P75)]
Table 2. GnRH stimulation test and IGF-1 test in children of different genders and ages[M(P25, P75)]
性别 年龄/岁 人数 统计值 LH基础值/(IU·L-1) LH峰值/(IU·L-1) FSH峰值/(IU·L-1) LH/FSH峰值比 IGF-1值/(IU·L-1) 男童 9 122 0.49(0.19, 0.62) 10.11(5.76, 14.14) 8.35(6.45, 10.59) 1.00(0.72, 1.58) 234.00(190.00, 270.00) 10 186 0.68(0.16, 1.13) 9.16(5.53, 18.60) 7.17(5.27, 8.55) 1.78(0.42, 2.92) 230.00(179.00, 322.00) 11 222 1.07(0.56, 1.55) 12.68(10.96, 20.60) 7.10(4.22, 8.51) 2.43(1.72, 2.17) 268.00(195.00, 341.00) 12 129 1.53(1.30, 2.44) 17.28(13.17, 20.80) 6.80(5.63, 9.58) 2.38(2.12, 2.58) 253.00(190.00, 370.00) 13~13.7 43 1.76(1.00, 2.47) 18.84(15.41, 21.40) 6.19(5.01, 10.19) 3.07(2.20, 3.46) 351.00(254.00, 430.00) 合计 702 1.00(0.47, 1.67) 13.22(8.38, 20.54) 7.22(5.27, 9.39) 2.13(1.00, 3.04) 251.00(185.00, 341.00) H值 218.11 110.57 34.02 121.10 35.80 女童 8 378 0.50(0.29, 1.38) 11.22(5.99, 24.00) 12.92(7.45, 15.74) 1.18(0.60, 1.87) 221.00(171.00, 273.00) 9 383 1.22(0.51, 3.10) 26.15(16.27, 35.69) 13.73(10.12, 16.52) 2.22(1.36, 2.61) 272.00(222.00, 401.00) 10 184 1.57(0.59, 2.84) 25.43(13.58, 49.18) 13.46(10.10, 16.47) 2.11(0.91, 3.57) 284.00(221.00, 387.00) 11 61 2.77(1.46, 4.11) 34.68(22.60, 45.02) 11.70(10.18, 13.55) 3.30(2.50, 3.86) 317.00(279.00, 397.00) 12~12.6 16 3.35(3.26, 4.58) 37.56(33.81, 72.53) 13.65(11.80, 19.87) 2.86(2.75, 3.65) 341.00(302.00, 403.00) 合计 1 022 1.04(0.41, 2.37) 21.79(9.52, 35.69) 13.02(9.86, 16.09) 1.87(0.92, 2.61) 257.00(196.00, 342.00) H值 161.86 158.74 23.34 173.72 150.22 注:P值均 < 0.01。 表 3 晨血LH及IGF-1对男童青春期启动的筛查效能分析
Table 3. The screening efficacy analysis of morning serum LH and IGF-1 on puberty initiation in boys
自变量/(IU·L-1) 筛查切值点 青春期启动人数 灵敏度 特异度 正确数 阳性似然比 阴性似然比 一致率 Kappa指数 晨血LH ≥0.23 548 0.92 0.73 0.65 3.44 0.11 0.89 0.60 < 0.23 49 IGF-1 ≥187.00 491 0.82 0.77 0.59 3.60 0.23 0.81 0.45 < 187.00 106 晨血LH≥0.23且 464 0.78 0.94 0.72 13.60 0.24 0.80 0.48 IGF-1≥187.00 133 晨血LH≥0.23或 575 0.96 0.52 0.49 2.02 0.07 0.90 0.55 IGF-1≥187.00 22 表 4 晨血LH及IGF-1对女童青春期启动的筛查效能分析
Table 4. The screening efficacy analysis of morning serum LH and IGF-1 on puberty initiation in girls
自变量/(IU·L-1) 筛查切值点 青春期启动人数 灵敏度 特异度 正确数 阳性似然比 阴性似然比 一致率 Kappa指数 晨血LH ≥0.22 833 0.96 0.65 0.62 2.77 0.06 0.92 0.66 < 0.22 31 IGF-1 ≥178.00 787 0.91 0.56 0.47 2.06 0.16 0.86 0.46 < 178.00 77 晨血LH≥0.22且 776 0.90 0.85 0.75 6.17 0.12 0.89 0.64 IGF-1≥178.00 88 晨血LH≥0.22或 863 1.00 0.35 0.35 1.55 < 0.01 0.90 0.48 IGF-1≥178.00 1 -
[1] HEO S, LEE Y S, YU J. Basal serum luteinizing hormone value as the screening biomarker in female central precocious puberty[J]. Am Pediatr Endocrinol Metab, 2019, 24(3): 164-171. doi: 10.6065/apem.2019.24.3.164 [2] 孙曼青, 陆文丽, 王伟, 等. 女童快速进展型中枢性性早熟早期预警及随访标志物的多中心研究[J]. 中华内分泌代谢杂志, 2017, 33(4): 312-316. doi: 10.3760/cma.j.issn.1000-6699.2017.04.008SUN M Q, LU W L, WANG W, et al. A multi-center clinical study of early predictors and follow-up parameters for girls with rapidly progressive central precocious puberty[J]. Chin J Endocrinol Metab, 2017, 33(4): 312-316. doi: 10.3760/cma.j.issn.1000-6699.2017.04.008 [3] KIM Y J, KWON A, JUNG M K, et al. Incidence and prevalence of central precocious puberty in korea: an epidemiologic study based on a national database[J]. J Pediatr, 2019, 208(3): 221-228. [4] 梁雁, 杜敏联, 罗小平. 中枢性性早熟诊断与治疗共识(2015)[J]. 中华儿科杂志, 2015, 53(6): 412-418. doi: 10.3760/cma.j.issn.0578-1310.2015.06.004LIANG Y, DU M L, LUO X P. Consensus on diagnosis and treatment of central precocious puberty (2015)[J]. Chin J Pediatr, 2015, 53(6): 412-418. doi: 10.3760/cma.j.issn.0578-1310.2015.06.004 [5] 陈荣华, 赵正言. 儿童保健学[M]. 5版. 南京: 江苏凤凰科学技术出版社, 2017: 106.CHEN R H, ZHAO Z Y. Child health science[M]. 5 ed. Nanjing: Jiangsu Phoenix Science and Technology Press, 2017: 106. [6] VNSAL V V, EBRU E A. Wnt pathway: a mechanism worth considering in endocrine disrupting chemical action[J]. Toxicol Ind Health, 2020, 36(1): 41-53. doi: 10.1177/0748233719898989 [7] 罗交, 陈燕容, 段若男, 等. 女孩青春期启动及发育趋势分析[J]. 卫生研究, 2015, 44(6): 1013-1018, 1046. https://www.cnki.com.cn/Article/CJFDTOTAL-WSYJ201506034.htmLUO J, CHEN Y R, DUAN R N, et al. Analysis of puberty initiation and developmental trends in girls[J]. J Hyg Res, 2015, 44(6): 1013-1018, 1046. https://www.cnki.com.cn/Article/CJFDTOTAL-WSYJ201506034.htm [8] 罗交, 唐宇帆, 段若男, 等. 男生青春期启动及发育趋势[J]. 中国学校卫生, 2015, 36(11): 1756-1760. http://www.cjsh.org.cn/article/id/zgxxws201511054LUO J, TANG Y F, DUAN R N, et al. The initiation and developmental trend of puberty in boys[J]. Chin J Sch Health, 2015, 36(11): 1756-1760. http://www.cjsh.org.cn/article/id/zgxxws201511054 [9] 王卫平, 孙锟, 常立文. 儿科学[M]. 9版. 北京: 人民卫生出版社, 2020: 401-402.WANG W P, SUN K, CHANG L W. Pediatrics[M]. 9 ed. Beijing: People's Health Publishing House, 2020: 401-402. [10] 唐海飞, 王智文, 郑雪松, 等. 雌激素功能研究进展[J]. 中华生殖与避孕杂志, 2019, 39(4): 334-340. https://www.cnki.com.cn/Article/CJFDTOTAL-SPKX202107001.htmTANG H F, WANG Z W, ZHENG X S, et al. Research progress of estrogen function[J]. Reprod Contracep, 2019, 39(4): 334-340. https://www.cnki.com.cn/Article/CJFDTOTAL-SPKX202107001.htm [11] 王晋, 罗红, 庞厚清, 等. 儿童至青春期子宫卵巢超声测值及超声对性早熟的诊断价值[J]. 四川大学学报(医学版), 2019, 50(4): 583-587. https://www.cnki.com.cn/Article/CJFDTOTAL-HXYK201904027.htmWANG J, LUO H, PANG H Q, et al. Ultrasound measurement of uterus and ovary in children to puberty and the diagnostic value of ultrasound in precocious puberty[J]. J Sichuan Univ (Med Ed), 2019, 50(4): 583-587. https://www.cnki.com.cn/Article/CJFDTOTAL-HXYK201904027.htm [12] XU Y J, XIONG J Y, GAO W K, et al. Dietary fat and polyunsaturated fatty acid intakes during childhood are prospectively associated with puberty timing independent of dietary protein[J]. Nutrients, 2022, 14(2): 275-286. doi: 10.3390/nu14020275 [13] 杨蓉, 马梅, 王子健. 雌激素干扰物的联合毒性研究进展[J]. 生态毒理学报, 2020, 15(5): 18-27. https://www.cnki.com.cn/Article/CJFDTOTAL-STDL202005002.htmYANG R, MA M, WANG Z J. Recent research advances in joint toxicity of estrogenic disruptors[J]. Asian J Ecotoxicol, 2020, 15(5): 18-27. https://www.cnki.com.cn/Article/CJFDTOTAL-STDL202005002.htm [14] ROSENFIELD R L. Normal and premature adrenarche[J]. Endocr Rev, 2021, 42(6): 783-814. doi: 10.1210/endrev/bnab009 [15] SEMAAN S J, KAUFFMAN A S. Developmental sex differences in the peri-pubertal pattern of hypothalamic reproductive gene expression, including Kiss1 and Tac2, may contribute to sex differences in puberty onset[J]. Mol Cell Endocrinol, 2022, 551: 111654. doi: 10.1016/j.mce.2022.111654 [16] NATALIE G A, KANTHI B K, PETER A. Use of gonadotropin-releasing hormone analogs in children[J]. Curr Opin Pediatr, 2021, 33(4): 442-448. doi: 10.1097/MOP.0000000000001026 [17] 朱俊. 儿童IGF-1浓度与骨龄及年龄的相关性研究[J]. 交通医学, 2019, 33(6): 636-637. https://www.cnki.com.cn/Article/CJFDTOTAL-JTYX201906034.htmZHU J. Study on the correlation between IGF-1 concentration and bone age and age in children[J]. Traffic Med, 2019, 33(6): 636-637. https://www.cnki.com.cn/Article/CJFDTOTAL-JTYX201906034.htm [18] KHAN L. Puberty: onset and progression[J]. Pediatr Ann, 2019, 48(4): e141-e145. [19] ENZA G, ROSA L, STEFANO C, et al. Linear growth and puberty in childhood obesity: what is new?[J]. Minerv Pediatr, 2021, 73(6): 563-571. -

计量
- 文章访问数: 360
- HTML全文浏览量: 185
- PDF下载量: 22
- 被引次数: 0