目的 探讨kisspeptin在鉴别下丘脑-垂体-性腺轴(HPGA)启动与否中的作用,以期简化性早熟的诊断流程。方法 选取四川大学华西第二医院儿科门诊2021年6月-2023年6月初诊以乳房发育为主诉的54名女童作为研究对象,进行体格检查、实验室检查和影像学检查等,采用酶联免疫吸附测定(ELISA)试剂盒检测kisspeptin水平。采用受试者工作特征曲线(ROC)确定kisspeptin在鉴别HPGA启动与否中的价值。结果 中枢性性早熟(CPP)组、快进展型青春期(RPP)组以及单纯乳房早发育(PT)组的kisspeptin水平差异有统计学意义(H=14.147,P=0.003)。Spearman相关性分析结果显示,kisspeptin水平与身高、体重、骨龄、基础黄体生长素(LH)、基础卵泡刺激素(FSH)、促性腺激素释放激素(GnRH)激发试验的LH峰值以及LH/FSH峰值比呈正相关(P<0.05),其中与LH峰值(rs=0.479)及LH/FSH峰值比(rs=0.507)的相关系数最大;ROC曲线结果显示,kisspeptin的曲线下面积(AUC)为0.702(95%CI:0.570~0.834),当截点值为310.38ng/mL时,Youden指数最大(0.418),此时的敏感度和特异度分别为81.8%和60.0%。结论 Kisspeptin在鉴别HPGA启动与否中有一定的诊断意义,可以作为HPGA启动与否的辅助诊断指标或初筛指标,为今后简化性早熟的诊断提供一定的参考和方向。
Abstract
Objective To explore the role of kisspeptin in identifying the activation of the hypothalamic-pituitary-gonadal axis (HPGA),in order to simplify the diagnostic process for precocious puberty. Methods A total of 54 girls who presented with breast development as the main complaint in the pediatric outpatient clinic of West China Second Hospital from June 2021 to June 2023 were selected as the study subjects.Physical examination,laboratory tests,and imaging examinations were conducted.The level of kisspeptin was detected using an enzyme-linked immunosorbent assay (ELISA) kit.The diagnostic value of kisspeptin in discerning the initiation of HPGA was determined via receiver operating characteristic (ROC) curve analysis. Results Significant differences in kisspeptin levels were observed among central precocious puberty (CPP),rapidly progressive puberty (RPP),and premature thelarche (PT) groups (H=14.147,P=0.003).Spearman correlation analysis revealed positive correlations between kisspeptin level and parameters such as height,weight,bone age,basal luteinizing hormone(LH),basal follicle-stimulating hormone(FSH),peak LH in gonadotropin-releasing hormone (GnRH) stimulation test,and LH/FSH peak ratio (P<0.05),with the largest correlation coefficients for LH peak (rs=0.479) and LH/FSH peak ratio (rs=0.507).The ROC curve showed that the area under the curve (AUC) of kisspeptin was 0.702 (95%CI:0.570 - 0.834).When the cut-off value was 310.38ng/mL,the Youden index was maximized (0.418),with a sensitivity and specificity of 81.8% and 60.0%,respectively. Conclusion Kisspeptin has diagnostic significance in differentiating the initiation of HPGA,and it can be used as an auxiliary diagnostic indicator or preliminary screening indicator,which can provide certain references and direction for simplifying the diagnosis procedure of precocious puberty in the future.
关键词
kisspeptin /
中枢性性早熟 /
快进展型青春期 /
下丘脑-垂体-性腺轴 /
ROC曲线
Key words
kisspeptin /
central precocious puberty /
rapidly progressive puberty /
hypothalamic-pituitary-gonadal axis /
ROC curve
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参考文献
[1] Ojeda SR,Lomniczi A.Puberty in 2013:Unravelling the mystery of puberty[J].Nat Rev Endocrinol,2014,10(2):67-69.
[2] Teles MG,Silveira LF,Tusset C,et al.New genetic factors implicated in human GnRH-dependent precocious puberty:The role of kisspeptin system[J].Mol Cell Endocrinol,2011,346(1-2):84-90.
[3] Lee JH,Miele ME,Hicks DJ,et al.KISS-1,a novel human malignant melanoma metastasis-suppressor gene[J].J Natl Cancer Inst,1996,88(23):1731-1737.
[4] Cortés ME,Carrera B,Rioseco H,et al.The role of kisspeptin in the onset of puberty and in the ovulatory mechanism:A mini-review[J].J Pediatr Adolesc Gynecol,2015,28(5):286-291.
[5] Gajdos ZK,Henderson KD,Hirschhorn JN,et al.Genetic determinants of pubertal timing in the general population[J].Mol Cell Endocrinol,2010,324(1-2):21-29.
[6] Gajdos ZK,Hirschhorn JN,Palmert MR.What controls the timing of puberty? An update on progress from genetic investigation[J].Curr Opin Endocrinol Diabetes Obes,2009,16(1):16-24.
[7] Neely EK,Crossen SS.Precocious puberty[J].Curr Opin Obstet Gynecol,2014,26(5):332-338.
[8] 中华医学会儿科学分会内分泌遗传代谢学组.中枢性性早熟诊断与治疗专家共识(2022)[J].中华儿科杂志,2023,61(1):16-22.
The Sabspeciality Group of Endocrinologic,Hereditary and Metabolic Diseases,the society of Pediatrics.Expert consensus on the diagnosis and treatment of central precocious puberty(2022)[J].Chin J Pediatr,2023,61(1):16-22.(in Chinese)
[9] 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.
Luo XP.Consensus on diagnosis and treatment of central precocious puberty(2015)[J].Chin J Pediatr,2015,53(6):412-418.(in Chinese)
[10] Lazar L,Kauli R,Pertzelan A,et al.Gonadotropin-suppressive therapy in girls with early and fast puberty affects the pace of puberty but not total pubertal growth or final height[J].J Clin Endocrinol Metab,2002,87(5):2090-2094.
[11] Ilahi I,Haq TU.MINI REVIEW:Role of Kisspeptin-GPR54 system in regulation of reproductive functions in human and other mammals[J].Pak J Pharm Sci,2021,34(1):177-184.
[12] Silveira LG,Noel SD,Silveira-Neto AP,et al.Mutations of the KISS1 gene in disorders of puberty[J].J Clin Endocrinol Metab,2010,95(5):2276-2280.
[13] Teles MG,Bianco SD,Brito VN,et al.A GPR54-activating mutation in a patient with central precocious puberty[J].N Engl J Med,2008,358(7):709-715.
[14] Cintra RG,Wajnsztejn R,Trevisan CM,et al.Kisspeptin levels in girls with precocious puberty:A systematic review and Meta-analysis[J].Horm Res Paediatr,2020,93(11-12):589-598.
[15] Parlak M,Türkkahraman D,Ellidag HY,et al.Basal serum neurokinin B levels in differentiating idiopathic central precocious puberty from premature thelarche[J].J Clin Res Pediatr Endocrinol,2017,9(2):101-105.
[16] Vuralli D,Ciftci N,Demirbilek H.Serum kisspeptin,neurokinin B and inhibin B levels can be used as alternative parameters to distinguish idiopathic CPP from premature thelarche in the early stages of puberty[J].Clin Endocrinol (Oxf),2023,98(6):788-795.
[17] Xue J,Song W,Si M,et al.Serum kisspeptin and AMH levels are good references for precocious puberty progression[J].Int J Endocrinol,2020,2020:3126309.