重组人生长激素替代治疗对体脂含量的影响研究

目的分析重组人生长激素(rhGH)治疗生长激素缺乏症(GHD)后患儿体质量变化的规律及原因;寻找rhGH替代治疗后便捷、灵敏地监测脂代谢变化的指标,了解机体脂代谢变化与rhGH疗效的相关性。方法随机选择完全性生长激素缺乏症(GHD)患儿15例,给予rhGH0.033mg/(kg·d)治疗,疗程6个月。观察用药前后身高(Ht)、生长速度(GV)、身高标准差积分(HtSDS)的变化,评价rhGH的促生长作用;测量治疗前、治疗3个月后、治疗6个月后的体质量(Wt)、体脂含量(Fat%)、体质指数(BMI)、腰臀比(WHR),检测治疗前、治疗6个月后的血脂水平,评价GHD患儿rhGH治疗前、后脂代谢状况。分析rhGH治疗后机体脂代谢变化与rhGH疗效的相关性。结果治疗后患儿Ht、GV、HtSDS改善显著(P<0.01),rhGH促生长作用肯定;治疗后患儿Fat%、血HDL、LDL水平较治疗前显著下降(P<0.05),机体脂代谢得到改善;rhGH治疗3个月与治疗6个月的ΔFat%与ΔGV存在负相关性(r=-0.625,P=0.0096)。结论rhGH治疗GHD后的体质量增长,为非脂肪的增长;体脂含量监测便捷无创,较血脂...     

不同剂量重组人生长激素治疗小于胎龄儿矮小症的疗效分析

目的 研究不同剂量重组人生长激素(rhGH)治疗小于胎龄儿(SGA)矮小症的效果和安全性。方法 收集SGA 矮小症患儿37 例,并根据使用剂量分为2 组:小剂量(每日0.1~0.15 IU/kg)rhGH 治疗组和大剂量rhGH 治疗组(每日0.16~0.2 IU/kg),比较两组患儿治疗后3、6、9、12 及24 个月时身高标准差的增长值(ΔHtSDS)、生长速率(HV)、血清胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)水平及空腹血糖等指标的变化。结果 大、小剂量rhGH 治疗后ΔHtSDS 及HV 均有提高,但大剂量组治疗后9、12 及24 个月时ΔHtSDS 及HV 均高于小剂量组(P<0.05)。大剂量和小剂量的rhGH 治疗均使血清IGF-1 和IGFBP-3 水平提高,且血清IGF-1 和IGFBP-3 水平与HtSDS 呈正相关。大小剂量组各有1 例患儿出现一过性空腹血糖轻微升高(均为6.1 mmol/L);两组甲状腺功能均无异常。结论 rhGH 治疗SGA 矮小症效果确切,不良反应少,其中大剂量较小剂量治疗更具优势。     

重组人生长激素对不同生长激素分泌状态青春前期矮小患儿近期疗效分析

目的探讨部分性生长激素缺乏症（pGHD）患儿在重组人生长激素（rhGH）治疗后早期追赶性生长的规律。方法回顾性分析62例青春前期不同生长激素（GH）分泌状态矮小患儿用rhGH治疗后,近期（1．5年）追赶性生长指标（生长速度和身高Z分增值）和促生长素轴实验室指标的变化。其中,完全性生长激素缺乏症（cGHD）27例;非GH缺乏性矮小（NGHD）12例;pGHD23例,按GH激发峰值7ng／ml分为pGHD-1（12例）和pGHD-2（11例）两个亚组。结果cGHD和NGHD初始追赶性生长的幅度相似,但NGHD组持续时间较短。pGHD和cGHD以同一rhGH生理替代量治疗后,促生长的应答（生长速度和AIGFBP-3SDS）pGHD-1和cGHD差异无统计学意义,但pGHD-2却低于cGHD,而与NGHD差异无统计学意义。结论GH激发试验的诊断界值选用7ng／ml有更合理的依据,诊断pGHD时尤应审慎。pGHD-2组治疗早期的生长追赶不完全可能与rhGH剂量相对不足有关。     

重组人生长激素治疗特发性矮小12个月疗效评估

目的 分析重组人生长激素(rhGH)对特发性矮小（ISS）患儿的治疗效果和影响因素,为寻求优化治疗效果的途径提供参考依据。 方法 回顾性分析2003年2月至2011年7月在首都儿科研究所生长发育门诊确诊为ISS患儿的临床资料,依据是否予rhGH治疗分为rhGH组和对照组。以身高标准差变化（ΔHtSDS）和生长速度（GV）作为评估指标进行疗效和影响因素分析。分析治疗期间骨龄、身高年龄及胰岛素样生长因子(IGF-1)水平的变化。 结果 rhGH组35例,对照组33例进入分析。①rhGH组治疗前、治疗后12个月HtSDS呈增长趋势(P<0.05);对照组均未见升高趋势。治疗后0～3个月的ΔHtSDS水平为(0.22±0.13),治疗后~6、~9和~12个月分别为(0.20±0.10)、(0.12±0.14)和(0.14±0.15),呈降低趋势,但差异无统计学意义。治疗后0～3个月GV为(10.78±2.70) cm·year-1,治疗后~6、~9和~12个月分别为(10.52±2.44)、(8.31±2.78)和(8.50±2.29) cm·year-1,呈降低趋势,但差异无统计学意义。治疗后0~6个月ΔHtSDS和GV水平均显著高于～12个月［ΔHtSDS :(0.43±0.20) vs (0.27±0.24), GV: (10.48±2.17) vs (8.48±2.39) cm·year-1］。②治疗后12个月的ΔHtSDS水平与治疗开始时的年龄呈负相关,与治疗后0～3个月的ΔHtSDS呈正相关;治疗后12个月的GV水平与治疗前的GH峰值和治疗后3个月的GV水平呈负相关。③治疗后1年青春期前、青春早中期和青春后期ΔHtSDS差异总体上有统计学意义（P=0.016）,其中青春期前显著高于青春早中期和青春后期;GV差异无统计学意义。④rhGH组治疗后12个月的骨龄变化差异无统计学意义,身高年龄显著高于对照组。⑤rhGH组IGF-1水平在治疗后1个月升高较明显,之后升高趋势减缓。 结论 rhGH用于ISS患儿的治疗应尽量选择青春期前;治疗后3个月的效果可作为第1年治疗效果的预测因素;rhGH治疗不会使ISS患儿骨龄明显提前。     

��������������������������ȱ��֢��Ч������Ԥ��ģ��̽��

目的探讨重组人生长激素(recombinant human growth hormone,rhGH,简称GH)治疗生长激素缺乏症(growth hormone deficiency,GHD)患儿效果及影响因素,建立GH治疗效果预测模型。方法回顾性分析1996年8月至2010年9月首都儿科研究所生长发育门诊确诊为GHD和多垂体功能低下(multiple pituitary hormonedeficiency,MPHD)且接受规范GH治疗的矮身材患儿115例临床资料,采用2009年卫生部最新颁布的中国儿童体格发育标准对儿童身高、体重进行标化,标准差计算采用国际公认的LMS方法。以治疗过程中的身高标准差分值变化(delta in height SDS,ΔHtSDS)和生长速度(growth velocity,GV)为效果评价指标,进行疗效和影响因素分析。用多元回归方法以75例治疗满1年且随访较规律者为模型人群,建立治疗效果预测模型。同时前瞻性随访15例规范治疗的GHD患儿为模型验证对象,对模型进行验证。结果患儿治疗第1年身高平均增长(10.56±2.83)cm,ΔHtSDS升高0.93±0.52;治疗前3个月的ΔH...     

国产重组人生长激素治疗特发性矮身材患儿的疗效

目的观察重组人生长激素(rhGH)对特发性矮身材(ISS)患儿的促生长效果。方法选择矮身材患儿98例。按病因分为ISS组30例,生长激素缺乏症(GHD)组68例。二组患儿均予国产rhGH治疗,剂量分别为0.15、0.1 IU/(kg.d),每晚睡前皮下注射,疗程6个月。治疗前及治疗后3、6个月分别测定患儿的身高、体质量、骨龄,计算生长速度。结果治疗3、6个月二组生长速度均显著高于治疗前[ISS组:(7.3±2.9),(7.5±2.7),(3.5±2.1)cm年/,P<0.01;GHD组:(13.2±3.5),(13.5±3.6),(4.0±2.9)cm年/,P<0.01]。治疗6个月后ISS组27例身高增长,GHD组68例身高增长。治疗3、6个月二组同期的生长速度比较,GHD组高于ISS组(P<0.01)。结论国产rhGH治疗ISS患儿安全、总体有效,但疗效存在不均一性,且差于GHD患儿。     

基因重组人生长激素儿科临床规范应用的建议北大核心CSCD

1985年,基因重组人生长激素（recombinant human growth hormone,rhGH）问世,为广大矮身材患儿的治疗带来希望。随后,rhGH在临床得到迅速应用,其治疗的有效性得到广泛验证,关于rhGH的治疗范围、治疗方案、疗效以及安全性的研究日益深入。为规范rhGH的应用及矮身材儿童的诊治,     

从循证医学证据看生长激素促生长治疗的收益及风险

基因重组人生长激素（rhGH）自1985年上市以来,已经治疗了上百万矮身材患儿,适应证不断扩大。同时,超适应证用药及单纯为增高而用药的现象也越来越严重。为此,多个学术组织出台指南或共识期望规范rhGH的诊疗。rhGH治疗生长激素缺乏症（growth hormone deficiency,GHD）终身高获益最大,其他非GHD疾病包括特发性矮小、特纳综合征等应用rhGH促生长收益有限。rhGH长期应用的安全性尚存有争议,临床医生处方rhGH时应谨慎,做到规范化使用。     

基因重组人生长激素儿科临床规范应用的建议

1985年,基因重组人生长激素(recombinant human growth hormone,rhGH)问世,为广大矮身材患儿的治疗带来希望.随后,rhGH在临床得到迅速应用,其治疗的有效性得到广泛验证,关于rhGH的治疗范围、治疗方案、疗效以及安全性的研究日益深入.为规范rhGH的应用及矮身材儿童的诊治,中华医学会儿科学分会内分泌遗传代谢学组于1998年提出《对基因重组人生长激素在临床应用的建议》[1],2008年制定了《矮身材儿童诊治指南》[2].但目前临床上仍存在随意扩大rhGH应用范围、疾病诊断不规范、过度治疗等问题,从而给rhGH治疗带来诸多隐患.     

重组人生长激素治疗生长激素缺乏症疗效观察

目的 观察基因重组人生长激素(rhGH)对生长激素缺乏症(GHD)患儿的疗效。方法 对15例GHD患儿应用rhGH治疗,每晚睡前皮下注射0.1 IU/kg,疗程6个月。结果 患儿身高由治疗前109.3±9.9cm增加到115.5±11.3 cm;年身高生长速度由治疗前2.8±0.6cm/年增加到11.6±3.5cm/年。治疗期间除少数患儿出现亚临床甲状腺功能低下,注射部位有轻度反应外,未发现明显副作用。结论 皮下注射rhGH是治疗儿童GHD的一种安全有效的方法。     

Three-year data from a comparative study with recombinant human growth hormone in the treatment of short stature in young children with intrauterine growth retardation

Growth acceleration and bone maturation were studied for 3 y in 69 children with severe short stature and a history of intrauterine growth retardation (IUGR), to determine the effect of treatment with recombinant human growth hormone (r-hGH). The patients were enrolled in an open, multicentre trial and were randomly allocated to either the treated group (Group 1) or the control group (Group 2). The children in Group 1 were treated daily with 0.2 IU/kg/body weight (0.067 mg/kg) s.c, during 3 y and the children in Group 2 started the study with a 1-y observation period followed by a 3-y treatment period. At birth, their mean weight standard deviation score (SDS) was -2.5 and their mean length SDS -3.5. At baseline, the patients were prepubertal, non-GHdeficient, with no known dysmorphic features. Mean age was 4.5 y, bone age was 3.3 y, height SDS was -3.4, height velocity (HV) SDS was -1.6, and body mass index SDS was -1.4. After 1 y of treatment, linear HV in Group 1 increased in comparison with the pre-treatment period (from 5.7 ± 2.0 to 10.1 ± 1.7cm/y; p < 0:001)and with the firstyear of observation in Group2( p < 0:001). Increased HV was sustained during the second and third year of treatment and was significantly higher than at baseline. A similar growth pattern was seen during the 3y of GH treatment in Group 2. Mean height SDS for chronological age increased by 2.0 ± 0.7 in the two groups after 3 y of treatment. HV after 1 y of treatment was negatively correlated with growth velocity at baseline. Bone age remained retarded but increased with a mean of almost 4 y after 3y of treatment in both groups. Even at a dose that is three times the replacement dose treatment with r-hGH was well tolerated. From these results, we conclude that r-hGH treatment over 3 y can induce sustained catch-up growth in young children with severe short stature and a history of IUGR. Long-term studies are needed to assess ultimate effects on final height.     

特发性矮小患儿生长激素受体基因Ex3多态性与重组人生长激素疗效分析

目的：观察生长激素受体（GHR）基因Ex3多态性与重组人生长激素（rhGH）治疗青春期前特发性矮小（ISS）疗效间的相关性。方法：青春期前ISS患儿30例,均采用rhGH［0.116±0.02 IU/(kg/d)］治疗;其外周血白细胞中抽提基因组DNA,采用多重PCR扩增GHR基因Ex3区域。对不同基因型患儿治疗后生长速率（GV）、年龄对应身高标准差积分（HtSDSCA）及骨龄对应身高标准差积分（HtSDSBA）、预测终身高进行比较。结果：rhGH治疗半年后d3/d3基因型组GV较fl/fl基因型组明显增加［（6.3±1.6）cm/年 vs （3.4±0.5）cm/年,P<0.05］。结论：ISS患儿GHR Ex3基因型与rhGH促生长疗效存在一定关联,d3/d3等位基因型患儿用rhGH治疗后生长速率明显优于fl/fl等位基因型。［中国当代儿科杂志,2010,12（9）：730-733］     

Disproportionate growth following long-term growth hormone treatment in short children with X-linked hypophosphataemia

Abstract Three short prepubertal children with X-linked hypophosphataemia were treated with 1 IU recombinant human growth hormone (rhGH)/kg per weck sc in addition to calcitriol and phosphate supplementation over a period of 3 years. Improvement of height standard deviation score (SDS) ranged from 1.0–1.7 SD based on an increase in sitting height of 1.5–2.9 SD, whereas subischial leg length improved only slightly by 0.3–0.9 SD. In all three patients, renal phosphate threshold concentration increased slightly and transient hyperparathyroidism was noted.Conclusion Treatment of stunted children with X-linked hypophosphataemia is effective in improving growth velocity, but appears to aggravate the pre-existent disporportionate stature of such children.     

Circulating immunoreactive growth hormone releasing hormone concentrations and growth hormone response to growth hormone releasing hormone in short children

To study the role of peripheral immunoreactive growth hormone releasing hormone (ir-GHRH) concentrations and the GHRH test in the evaluation of growth hormone (GH) secretion in short stature, 46 children with a mean age of 9.4 years (range 1.6–16.3 years) and a mean relative height score of –3.2 SD (range –5.0–2.1 SD) were investigated. The children were divided into prepubertal (n=35) and pubertal (n=11) and the prepubertal children further into three groups based on their maximal GH responses to insulin-induced hypoglycaemia (IIH) and clonidine: (1) GH deficient subjects (maximal GH<10 g/l in both test); (2) discordant responders (maximal GH<10 g/l in one test and 10 g/l in the other); and (3) normal responders (maximal GH10 g/l in both test). Peripheral ir-GHRH concentrations were measured during the IIH test by radioimmunoassay after purification of plasma samples on Sep-pak cartridges. Among the prepubertal children 10 fell into group 1, 16 into group 2 and 9 into group 3. Children in group 1 were older, than those in group 3. There were no significant differences in relative heights and weights or absolute and relative growth velocities between the groups. Subjects in groups 1 and 2 had lower maximal GH responses to GHRH than those in group 3. There were no significant differences in the basal plasma ir-GHRH concentrations between the groups. Nine children (19.6%) had somatotrophs with a poor response to a single dose of exogenous GHRH (maximal GH<10 g/l). These subjects had increased basal plasma ir-GHRH concentrations. All of them had a decreased GH response to IIH and/or clonidine. Pubertal children had higher circulating ir-GHRH levels than the prepubertal subjects. There was an inverse correlation (r=–0.46;P<0.001) between the maximal GH response to GHRH and calendar age in the whole series. These observations suggest that: (1) a substantial proportion of short children have a heterogenous GH response to pharmacological stimuli necessitating complementary evaluation of their spontaneous GH secretion; (2) a poor response to exogenous GHRH is associated with increased ir-GHRH levels in the peripheral circulation; (3) all children with normal GH responses in pharmacological tests respond normally to GHRH and (4) the pituitary sensitivity to GHRH decreases with increasing age. Peripheral ir-GHRH concentrations do not differentiate between short children with growth hormone deficiency (GHD) and those with undefined short stature. The GHRH test is of limited value in the diagnosis of GHD, since a normal GH response does not exclude GHD, although a subnormal response appears to reflect dysfunctional GH secretion.     

Small for gestation and growth hormone therapy

3 to 10% of neonates are born small for gestation (SGA). This usually occurs because of intrauterine growth retardation (IUGR). After birth most SGA infants show good catch-up growth and normalize their height and weight. About 10% of them continue to remain short (<−2SD) and do not achieve normal adult, height, resulting in psychosocial problems. The mechanism of short stature in these children is poorly understood. Infants who do not show catch-up growth usually have an alteration in the GH-IGF-I axis. Diagnostic and management criteria for short stature in SGA were ill-defined in the past. Growth hormone (GH) therapy for improving height in these children has been approved by the FDA. GH therapy leads to growth acceleration and normalization of height during childhood. Long term GH treatment normalizes adult height above-2 SDS in 85% children, and 98% achieve an adult height within their target height range. GH therapy is safe in SGA children, but it is important to monitor for side effects.     

Growth hormone treatment of short children born small for gestational age: metanalysis of four independent, randomized, controlled, multicentre studies

A minority of children born small for gestational age (SGA) fail to achieve sufficient catch-up growth during infancy and remain short throughout childhood, apparently without being growth hormone (GH) deficient. The effect of GH administration was evaluated over 2 years in short prepubertal children born SGA. The children ( n = 244), who were taking part in four independent multicentre studies, had been randomly allocated to groups receiving either no treatment or GH treatment at a daily dose of 0.1, 0.2 or 0.3 IU/kg (0.033, 0.067 or 0.1 mg/kg) s.c. At birth, their mean length SD score (SDS) was -3.6 and their mean weight SDS -2.6; at the start of the study, mean age was 5.2 years, bone age 3.8 years, height SDS -3.3, height SDS adjusted for parental height -2.4, weight SDS -4.7 and body mass index (BMI) SDS -1.4. The untreated children had a low-normal growth velocity and poor weight gain. Although bone maturation progressed more slowly than chronological age, final height prognosis tended to decrease, according to height SDS for bone age. GH treatment induced a dose-dependent effect on growth, up to a near doubling of height velocity and weight gain; BMI SDS was not altered. Bone maturation was also accelerated differentially; however, final height prognosis increased in all GH treatment groups. The more pronounced growth responses were observed in younger children with a lower height and weight SDS. In conclusion, GH administration is a promising therapy for normalizing short stature and low weight after insufficient catch-up growth in children born SGA. Long-term strategies incorporating GH therapy now remain to be established.     

Short- and long-term (final height) data in children with normal variant short stature treated with growth hormone

Seventeen children with normal variant short stature and a predicted height below −2 SDS were treated with growth hormone (GH) six times a week for a period of 5 years. Patients were randomly selected to receive three different doses of GH, group 1 (n=6) 3␣IU/m² per day, group 2 (n=6) 4.5 IU/m² per day and group 3 (n=5) 3 IU/m² per day in the 1st year and 4.5␣IU/m² per day thereafter. There was a significant increase in height after 1 and 2 years for all patients and for all subgroups. However, this increase was not dependent on GH dose. The decrease in height velocity during the 2nd year was not prevented by the increase of GH dose in group 3. The change of predicted height after 2 years was +0.75 SDS (according to Tanner Whitehouse). Fourteen children have been treated for 4␣years and 8 children for 5 years without a further change in height prediction. Nine patients have reached final height which was 2.4 cm (+0.41 SDS) above pretreatment height prediction. Final height was nearly identical to predicted height after 1 year of therapy. Conclusion An increment in height prediction was observed during the first 2 years of GH treatment and maintained thereafter. However, there was only a minor increase in final height over predicted height which does not justify the general use of GH in children with normal variant short stature. Received: 19 December 1996 / Accepted: 21 February 1997