促性腺激素释放激素类似物联合重组人生长激素对大骨龄中枢性性早熟儿童身高的改善效果及其影响因素

Effect of Gonadotropin-releasing Hormone Analogue Combined with Recombinant Human Growth Hormone on Height Improvement and Its Influencing Factors in Older Children with Central Precocious Puberty

目的探讨促性腺激素释放激素类似物联合重组人生长激素对大骨龄中枢性性早熟儿童身高的改善效果及其影响因素。方法选取2020年1月至2022年7月于南方医科大学顺德医院诊断为大骨龄中枢性性早熟儿童60例作为研究对象,随机分为对照组20例、A观察组19例、B观察组21例。对照组未进行任何治疗,A观察组单纯给予醋酸曲普瑞林治疗,B观察组采用醋酸曲普瑞林联合注射用重组人生长激素进行治疗。每3个月测量儿童身高,每6个月进行骨龄检查、性激素指标[血清黄体生成素(LH)、卵泡刺激素(FSH)、雌二醇(E_(2))]及骨代谢指标[血清Ⅰ型胶原羧基端肽β特殊序列(β-CTX)、N端骨钙素(N-MID)]检测,比较3组儿童治疗后身高净获值差异,采用单因素及多因素多元逐步Logistic回归分析法分析身高净获值的影响因素。结果治疗后B观察组患儿身高净获值为(8.20±2.44)cm,A观察组为(4.42±1.60)cm,对照组为(2.12±0.90)cm,B观察组身高净获值明显高于A观察组和对照组(P<0.05),A观察组明显高于对照组(P<0.05)。随访期结束后(GnRha激发试验60 min数值),A观察组、B观察组血清LH、FSH、E_(2)明显低于对照组(P<0.05),B观察组血清LH、FSH、E_(2)明显低于A观察组(P<0.05)。随访期结束后,A观察组、B观察组血清β-CTX、N-MID明显低于对照组(P<0.05),B观察组血清β-CTX、N-MID明显低于A观察组(P<0.05)。Person直线相关性分析显示,用药初始年龄、用药初始骨龄、用药初始身高标准差积分(Ht SDS)、LH、FSH、E_(2)、β-CTX、N-MID与身高净获值负相关,r分别为-0.269、-0.118、-0.299、-0.181、-0.217、-0.153、-0.188、-0.289。多元逐步Logistic回归分析显示用药初始年龄、用药初始骨龄、用药初始HtSDS、LH、FSH、E_(2)、β-CTX、N-MID是影响性腺激素释放激素类似物联合注射用重组人生长激素治疗对大骨龄中枢性性早熟儿童身高改善效果的重要因素。结论促性腺激素释放激素类似物联合重组人生长激素能有效提高大骨龄中枢性性早熟儿童身高,作用机制可能与其改善血清骨代谢标志物及性激素水平有关,其主要影响因素为用药初始年龄、用药初始骨龄、用药初始HtSDS、骨代谢标志物及性激素水平。

Objective To investigate the effect of gonadotropin-releasing hormone analogue combined with recombinant human growth hormone on the improvement of height of children with central precocious puberty at the age of bone and its influencing factors.Methods Children diagnosed with central precocious puberty of large bone age at Shunde Hospital of Southern Medical University from January 2020 to July 2022 were randomly divided into control group(20 cases),observation group A(19 cases)and observation group B(21 cases).The control group did not receive any treatment,observation group A was simply treated with triprorelin acetate,injected once every 4 weeks for 2 consecutive years,observation group B was treated with triprorelin acetate combined with recombinant human growth hormone for injection,in which triprorelin acetate was treated with the same treatment as observation group A,injected once every 4 weeks,recombinant human growth hormone for injection was treated according to the weight of the child in kg.The initial therapeutic dose was 0.15 iu/kg.d.The height of the children was measured every 3 months,and bone age(BA),sex hormone(LH),follicle-stimulating hormone(FSH),estradiol(E_(2))and bone metabolism(serum type I collagen carboxy-terminal peptideβspecial sequence(β-CTX),N-terminal osteocalcin(N-MID))were tested every 6 months.The difference of net height gain in the three groups after treatment was compared,and the influencing factors of net height gain were analyzed by single factor and multiple factor Logistic stepwise regression analysis.Results The net gain of height after treatment was(8.20±2.44)cm in observation group B,(4.42±1.60)cm in observation group A and(2.12±0.90)cm in control group,and the difference was statistically significant(F=59.926,P<0.05).The net gain of height after treatment in observation group B was significantly higher than that in observation group A and control group(P<0.05),and the net gain of height after treatment in observation group A was significantly higher than that in control group(P<0.05).After the end of the follow-up period(GnRha stimulation test for 60 minutes),the differences of LH,FSH and E_(2)in control group,observation group A and observation group B were statistically significant(P<0.05),and the LH,FSH and FSH in observation group A and observation group B were significantly lower than those in control group(P<0.05).LH,FSH and FSH in observation group B were significantly lower than those in observation group A(P<0.05).After the end of the follow-up period,theβ-CTX and N-MID of the control group,observation group A and observation group B had statistical significance(P<0.05).Theβ-CTX and N-MID of observation group A and observation group B were significantly lower than those of the control group(P<0.05),and theβ-CTX and N-MID of observation group B were significantly lower than those of observation group A(P<0.05).Person correlation analysis showed that age at the beginning of medication,bone age at the beginning of medication,HtSDS at the beginning of medication,LH,FSH,E_(2),β-CTX,N-MID were negatively correlated with net gain of height.r was-0.269,-0.118,-0.299,-0.181,-0.217,-0.153,-0.188,-0.289,respectively,all P<0.05.Multiple Logistic regression analysis showed that initial age of medication,initial bone age,initial HtSDS,LH,FSH,E_(2),β-CTX,N-MID were the influential factors affecting the height improvement effect of gonadotropin-releasing hormone analogues alone on central precocious puberty of large bone age children,all P<0.05.Conclusion Gonadotropinreleasing hormone analogues combined with recombinant human growth hormone can effectively improve the height of central precocious puberty children with large bone age,and the mechanism of action may be related to the improvement of serum bone metabolism markers and sex hormone levels.The main influencing factors are age at the beginning of medication,bone age at the beginning of medication,HtSDS at the beginning of medication,bone metabolism markers and sex hormone levels.