CAJ | 학술논문

目的：探讨生长激素（ growth hormone，GH）改善促性腺激素释放激素类似物（ gonadotropin-releasing hormone analogue，GnRHa）治疗中大骨龄、青春中后期中枢性性早熟（ central precocious puberty，CPP）或快速进展型早发育（early and fast puberty，EFP）女孩线性生长的近期疗效，以及C型利钠肽（C-type natriuretic peptide，CNP）在GH促线性生长机制中的作用。方法：22例骨龄≥11．5岁、预测成年身高（predicted adult height，PAH）严重受损、青春中后期的特发性CPP或EFP女孩分为2组各11例：（1）单用GnRHa组：仅用GnRHa（每4周缓释型曲普瑞林60～80μg/kg，im）治疗；（2）联用GH组：联用GnRHa和GH（每周1 U/kg，分6～7次睡前sc）治疗。每3个月测量身高和体重，检查性征；治疗开始和治疗6个月末行骨龄检查，并检测血清CNP氨基端前体（ amino-terminal pro-C-type natriuretic peptide，NTproCNP）、胰岛素样生长因子1（insulin-like growth factor 1，IGF-1）及1型前胶原氨基端伸展肽（ procollagen type 1 amino-terminal propeptide，P1NP）的浓度。比较治疗前及治疗后6个月的身高增长速度（height velocity，HV）、按骨龄身高的标准差分值（height SD score for bone age，HtSDSBA）、PAH及上述血清指标的变化。结果：（1）联用GH组治疗6个月的HV、HtSDSBA增值（ΔHtSDSBA ）和PAH增值（ΔPAH）均显著高于单用Gn-RHa组（P＜0．01）。（2）联用GH组治疗6个月末与治疗开始时比较，血清NTproCNP、P1NP浓度和IGF-1浓度均无显著性差异。（3）单用GnRHa组治疗6个月末的血清NTproCNP和P1NP浓度则均较治疗开始时显著下降（ P＜0．05），IGF-1浓度则无显著差异。结论：对于大骨龄、青春中后期的特发性CPP或EFP女孩，GnRHa联用GH能促进线性生长，有效改善预测成年身高。 GH的促生长作用不依赖于血清IGF-1水平的变化，而可能部分与CNP介导的长骨生长加速有关。目的：探討生長激素（ growth hormone，GH）改善促性腺激素釋放激素類似物（ gonadotropin-releasing hormone analogue，GnRHa）治療中大骨齡、青春中後期中樞性性早熟（ central precocious puberty，CPP）或快速進展型早髮育（early and fast puberty，EFP）女孩線性生長的近期療效，以及C型利鈉肽（C-type natriuretic peptide，CNP）在GH促線性生長機製中的作用。方法：22例骨齡≥11．5歲、預測成年身高（predicted adult height，PAH）嚴重受損、青春中後期的特髮性CPP或EFP女孩分為2組各11例：（1）單用GnRHa組：僅用GnRHa（每4週緩釋型麯普瑞林60～80μg/kg，im）治療；（2）聯用GH組：聯用GnRHa和GH（每週1 U/kg，分6～7次睡前sc）治療。每3箇月測量身高和體重，檢查性徵；治療開始和治療6箇月末行骨齡檢查，併檢測血清CNP氨基耑前體（ amino-terminal pro-C-type natriuretic peptide，NTproCNP）、胰島素樣生長因子1（insulin-like growth factor 1，IGF-1）及1型前膠原氨基耑伸展肽（ procollagen type 1 amino-terminal propeptide，P1NP）的濃度。比較治療前及治療後6箇月的身高增長速度（height velocity，HV）、按骨齡身高的標準差分值（height SD score for bone age，HtSDSBA）、PAH及上述血清指標的變化。結果：（1）聯用GH組治療6箇月的HV、HtSDSBA增值（ΔHtSDSBA ）和PAH增值（ΔPAH）均顯著高于單用Gn-RHa組（P＜0．01）。（2）聯用GH組治療6箇月末與治療開始時比較，血清NTproCNP、P1NP濃度和IGF-1濃度均無顯著性差異。（3）單用GnRHa組治療6箇月末的血清NTproCNP和P1NP濃度則均較治療開始時顯著下降（ P＜0．05），IGF-1濃度則無顯著差異。結論：對于大骨齡、青春中後期的特髮性CPP或EFP女孩，GnRHa聯用GH能促進線性生長，有效改善預測成年身高。 GH的促生長作用不依賴于血清IGF-1水平的變化，而可能部分與CNP介導的長骨生長加速有關。
목적：탐토생장격소（ growth hormone，GH）개선촉성선격소석방격소유사물（ gonadotropin-releasing hormone analogue，GnRHa）치료중대골령、청춘중후기중추성성조숙（ central precocious puberty，CPP）혹쾌속진전형조발육（early and fast puberty，EFP）녀해선성생장적근기료효，이급C형리납태（C-type natriuretic peptide，CNP）재GH촉선성생장궤제중적작용。방법：22례골령≥11．5세、예측성년신고（predicted adult height，PAH）엄중수손、청춘중후기적특발성CPP혹EFP녀해분위2조각11례：（1）단용GnRHa조：부용GnRHa（매4주완석형곡보서림60～80μg/kg，im）치료；（2）련용GH조：련용GnRHa화GH（매주1 U/kg，분6～7차수전sc）치료。매3개월측량신고화체중，검사성정；치료개시화치료6개월말행골령검사，병검측혈청CNP안기단전체（ amino-terminal pro-C-type natriuretic peptide，NTproCNP）、이도소양생장인자1（insulin-like growth factor 1，IGF-1）급1형전효원안기단신전태（ procollagen type 1 amino-terminal propeptide，P1NP）적농도。비교치료전급치료후6개월적신고증장속도（height velocity，HV）、안골령신고적표준차분치（height SD score for bone age，HtSDSBA）、PAH급상술혈청지표적변화。결과：（1）련용GH조치료6개월적HV、HtSDSBA증치（ΔHtSDSBA ）화PAH증치（ΔPAH）균현저고우단용Gn-RHa조（P＜0．01）。（2）련용GH조치료6개월말여치료개시시비교，혈청NTproCNP、P1NP농도화IGF-1농도균무현저성차이。（3）단용GnRHa조치료6개월말적혈청NTproCNP화P1NP농도칙균교치료개시시현저하강（ P＜0．05），IGF-1농도칙무현저차이。결론：대우대골령、청춘중후기적특발성CPP혹EFP녀해，GnRHa련용GH능촉진선성생장，유효개선예측성년신고。 GH적촉생장작용불의뢰우혈청IGF-1수평적변화，이가능부분여CNP개도적장골생장가속유관。
[ ABSTRACT] AIM:To investigate the effect of combined treatment with gonadotropin-releasing hormone analogue ( GnRHa) and growth hormone ( GH) on the linear growth in mid-and late pubertal girls at great bone ages with central precocious puberty ( CPP) or early and fast puberty ( EFP) , and to determine the relation between C-type natriuretic pep-tide ( CNP) signaling pathway and the accelerative effect of GH on long bone growth in these girls.METHODS:Twenty-two girls were diagnosed as CPP or EFP, whose bone ages were older than 11.5 years with impaired predicted adult height ( PAH) , and divided into GnRHa treatment group ( treated with GnRHa alone, slow-release of triptorelin 60~80 μg/kg every 4 weeks, im) and combined treatment group ( treated with GnRHa and GH, 1 U/kg GH every week for 6~7 times, sc) .The height, weight and pubertal stage were determined every 3 months.At the beginning and after 6 months of the treatment, the bone age was evaluated and the serum concentrations of amino-terminal pro-C-type natriuretic peptide ( NT-proCNP), insulin-like growth factor 1 (IGF-1) and procollagen type 1 amino-terminal propeptide (P1NP) were measured. Height velocity ( HV) , height SD score for bone age ( HtSDSBA ) , PAH and the serum indexes mentioned above were com-pared at the beginning and the end of the treatment.RESULTS: After 6 months of the treatment, HV, ΔHtSDSBA andΔPAH of the girls treated with GnRHa +GH were statistically higher than those of the girls given GnRHa alone ( P <0.01).Serum concentrations of NTproCNP, P1NP and IGF-1 were not significantly different between the beginning and the end of the 6-month combined treatment.The girls treated with GnRHa alone showed a significant decrease in both serum NTproCNP and P1NP levels (P<0.05) and no significant change of serum IGF-1 level after 6 months of the treatment. CONCLUSION:In the CPP or EFP girls who are in mid-and late puberty and at great bone ages, the combined treatment with GnRHa and GH may accelerate linear growth and improve predicted adult height.This effect of GH is not attributed to the change of serum IGF-1 level, and may be related in part to the acceleration of CNP-mediated long bone growth.