重组人生长激素治疗单纯性生长激素缺乏症和特发性矮小症患儿血清C型利钠肽氨基末端浓度与生长速率的变化

Changes of amino-terminal propeptide of C-type natriuretic peptide and growth velocity in patients with idiopathic short stature or isolated growth hormone deficiency after recombinant human growth hormone treatment

目的探讨单纯性生长激素缺乏症（isolated growth hormone deficiency, IGHD）以及特发性矮小症（idiopathic short stature，ISS）患儿经重组人生长激素（recombinant human growth hormone，rhGH）治疗后，血清C型利钠肽氨基末端（NTproCNP）浓度的变化及其与生长速率（growth velocity，GV）的关系。方法共有48例青春期前的患儿纳入研究（IGHD25例，ISS23例），并给予rhGH治疗1年。治疗前及治疗后6个月分别测血清胰岛素样生长因子-I（IGF—I）和NTproCNP的浓度。治疗1年后，计算所有患儿的GV、身高Z积分（HTSDS）以及身高Z积分的变化值（AHTSDS）。结果IGHD组中，治疗前后IGF—IZ积分的变化值（△IGF-ISDS）、NTproCNP浓度的变化值（△NTproCNP）与治疗1年中GV呈正相关（r=0．407，P=0．044；r=0．490，P=0．013）；治疗前生长激素（GH）峰值也与治疗前IGF—ISDS、NTproCNP浓度（r=0．558，P=0．004；r=0．630，P=0．001）以及治疗后△IGF-ISDS与△NTproCNP呈正相关（r=0．466，P=0．019）。而在ISS患儿中，治疗1年中GV只与治疗后△NTproCNP相关（r=0．845，P〈0．01）。结论在IGHD和ISS患儿应用rhGH的促生长治疗中，NTproCNP水平随着生长速率的增加而增加。因此除了IGF-I，NTproCNP作为一种新的生化标记物，也可用于评估和预测这两类患儿在rhGH治疗后的GV变化。

Objective To explore the value of amino-terminal propeptide of C-type natriuretic peptide （NTproCNP） in evaluating the efficacy of therapy with recombinant human growth hormone（rhGH） in patients with idiopathic short stature （ISS） and isolated growth hormone deficiency （IGHD）. Methods Forty-eight prepubertal children（ IGHD n=25, ISS n = 23 ） treated for at least 1 year with rhGH were included. Serum insulin-like growth factor- I （ IGF- I ） and NTproCNP levels were measured before starting treatment and 6 months later. Twelve months after starting treatment, all patients were assessed and annual growth velocity （ GV）, height standard deviation score （ HTSDS）, and gained HTSDS （AHTSDS） were recorded. Results In GHD group, positive relationships between GV and change of IGF- ISDS（ △IGF- ISDS ）, GV and change of NTproCNP concentrations（ANTproCNP） were found（ r = 0. 407, P = 0. 044 ; r = 0. 490, P = 0. 013 ）. GH peak value was also positively associated with IGF- ISDS and NTproCNP before therapy （ r = 0. 558, P = 0. 004; r = 0. 630, P = 0. 001 ）. △IGF- ISDS and △NTproCNP were positively associated after therapy （r=0.466,P=0.019）. In ISS group, GV was associated with ANTproCNP （ r= 0. 845, P〈 0.01 ）. Conclusions NTproCNP is a novel biomarker of growth as its level increases during growth-promoting treatment. Furthermore, IGF- I is also valuable in evaluating the efficacy of rhGH therapy in short stature patients.