内分泌系统疾病

071372重组人生长激素治疗生长激素缺乏症患儿影响生长速度疗效的因素/潘思年…∥中华儿科杂志.-2006,44(7).-544~54594例生长激素缺乏症(GHD)患儿治疗前年生长速度(GV)(4.4±1.6)cm,用重组人生长激素(rhGH)后,生长速度明显加快(P<0.01),以头6个月的GV最快,第2~5年GV渐降,但无统计学意义。相关分析提示:头6个月生长速度(GV1)与骨龄(BA0)、类胰岛素样生长因子(IGF-1)SDS、身高Z分值(HtSDS)和激发试验GH峰(SPGH)呈负相关。逐步回归分析显示:BA0和SPGH是影响GV1的独立因素。认为用rhGH治疗至少在头4年内能使GHD患儿呈现有效…     

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...     

重组人生长激素对青春后期特发性矮小女童促生长的疗效

目的探讨重组人生长激素(rhGH)对青春后期特发性矮小(ISS)女童的促生长效应。方法选取30例青春后期ISS女童。年龄12～14岁;身高143～149cm。分为治疗组和对照组,每组均为15例。治疗组患儿均单独接受GH治疗,治疗剂量为0.15IU.kg-1.d-1,临睡前皮下注射,疗程6个月;对照组未使用任何药物,观察6个月。结果治疗组生长速率(GV)由治疗前(2.20±0.56)cm.a-1提高至(3.40±1.37)cm.a-1,与对照组比较有统计学差异(P<0.05);骨龄(BA)由治疗前(13.3±1.7)岁增加到(13.9±1.6)岁,与对照组比较无统计学差异(P>0.05)。预测成年身高(PAH)由(146.2±3.1)cm提高到(149.3±3.4)cm,与对照组比较有统计学差异(P<0.05)。治疗组治疗前后GV和FAH比较差异均有统计学意义(Z=-2.05、-2.43,Pa<0.05);而BA比较差异无统计学意义(Z=0.65,P>0.05)。结论GH治疗能改善青春后期ISS女童的GV,而BA加速不明显,疗效肯定,无明显不良反应。     

重组人生长激素治疗特发性矮小患儿的疗效

目的 观察重组人生长激素( rhGH)治疗特发性矮小(ISS)的疗效.方法 2007年2月-2011年4月在本院儿科就诊并诊断为ISS的患儿62例.男38例,女24例；年龄5～12岁.每晚睡前皮下注射rhGH 0.15 IU· kg-1·d-1,观察1 a,自身比较生长速度(GV)、骨龄(BA)、体质量、身高、年龄对应的身高标准差积分( HtSDSCA)、BA对应的身高标准差积分(HtSDSBA)、BA/年龄( BA/CA)、预测成年身高(PAH)、胰岛素样生长因子-1(IGF-1)水平.结果 治疗1 a后,GV由治疗前(4.03±0.69) cm·a-1提高到(8.94±1.74) cm·a-1,身高由( 116.16±16.09) cm提高到(125.26±14.72) cm,HtSDSCA由-2.83±0.91提高到-2.07±0.94,HtSDSBA由0.21±1.01提高到1.14±1.25,PAH由(166.26±9.08) cm提高到(172.46±8.32) cm,治疗前后比较均有统计学差异.而BA、体质量、BA/CA 、IGF-1治疗前后比较差异均无统计学意义.结论 rhGH对ISS患儿促生长作用显著,且对BA无明显影响,不良反应少.     

基因重组生长激素治疗青春期前特发性矮小疗效观察

目的探讨基因重组人生长激素（rhGH）对青春期前特发性矮小（ISS）的疗效。方法观察27例青春期前特发性矮小患儿,平均年龄（8.9±2.0）岁,身高（118.0±10.6）cm。治疗组13例,男10例,女3例,均接受基因重组人生长激素治疗,剂量（0.12±0.01）IU/kg,睡前皮下注射,疗程6个月至1年;对照组14例,男6例,女8例。结果治疗组患儿生长速率（GV）由治疗前（4.28±0.86）cm/a提高到（9.38±1.77）cm/a,P〈0.01;年龄身高标准差积分（HtSDSCA）由-2.28±0.48增至-1.72±0.62（P〈0.01）;骨龄身高标准差积分（HtS-DSBA）由-0.24±1.02增至0.27±0.99（P〈0.05）;与对照组比较,GV、HtSDS（CA）和HtSDS（BA）差异均有统计学意义（P均〈0.05）;两组△BA/△CA比较差异无统计学意义（P均〉0.05）。结论GH治疗能改善ISS儿童的GV及HtSDS（CA）、HtSDS（BA）,而骨龄（BA）加速不明显,疗效肯定。     

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。     

重组人生长激素治疗青春中后期特发性矮小症临床观察

目的探讨重组人生长激素(rhGH)对青春中、后期特发性矮小症(ISS)患儿的促生长效应。 方法于2003-10—2005-03在天津市南开医院就诊的19例青春中、后期ISS患者按骨龄被分为3组,A组骨龄130~139岁,10例(男7,女3);B组骨龄140~149岁,6例(男4,女2);C组骨龄150~160岁,3例(男2,女1)。每晚睡前皮下注射rhGH018~020IU/kg,共6个月。 结果3组ISS患者的身高分别由治疗前(1384±12)cm、(1442±18)cm和(1528±44)cm增至(1444±16)cm、(1487±12)cm和(1553±65)cm。3组患儿于治疗的前3个月促生长效果较明显,后3个月A组的促生长效果明显高于B组、C组,且依次递减,组间生长速度差异有显著性意义(P<005);3组患儿用药前、后的体重、骨龄变化差异无显著性意义(P>005);所有患者用药前后的甲状腺功能、血糖、血尿常规均正常。 结论rhGH治疗对青春中后期特发性矮小症有促生长效应,但应密切随访。     

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］     

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。     

重组人生长激素治疗不同生长激素分泌状态青春前期矮身材患儿近期疗预测模型的建立和验证

目的 建立重组人生长激素(rhGH)治疗生长激素不同分泌状态青春前期矮身材患儿近期(1年)疗效的预测模型,并进行初步验证.方法回顾性分析62例生长激素不同分泌状态的青春前期矮身材患儿[模型组,分为全模型组(模型组全部病例)和生长激素缺乏症模型组(模型组中生长激素缺乏症的病例)]经rhGH治疗1年后的追赶性生长指标:生长速度(HV)和身高Z分增值(ΔHtSDS).根据单因素相关分析的结果,通过多元回归的方法,分别建立对HV和ΔHtSDS的2个预测方程(Model-GHD和Model-total).前瞻性分析另14例(验证组),将资料代入前述方程进行验证.结果单因素相关分析显示,与HV和ΔHtSDS显著(负)相关的是同一组影响因素.所得4个预测方程,R2在0.244～0.519,P值均＜0.05.HV的2个预测方程和对生长激素缺乏症患儿1ΔHtSDS的预测方程(实测值和预测值呈显著正相关,r在0.753～0.996;配对t检验示两者差异无统计学意义).结论预测模型建立成功,有助于预测不同生长激素分泌状态青春期矮身材患儿的生长激素的近期疗效.     

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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...     

Oxandrolone increases final height in Turner syndrome

Abstract In order to examine whether the anabolic steroid oxandrolone has any long-term effect on height in Turner syndrome, the short- and long-term effects were studied in a group of 35 individuals with the syndrome. At commencement of treatment, age range was 8.2–16 years (mean 12.9); oxandrolone dosage was 0.07-0.26 mg/kg per day (mean 0.14 mg/kg per day) and continued for 12 months-6 years (mean 33 months), ending at 12–18.5 years (mean 15.6 years). Height velocity increased significantly on therapy from 3.3 ± 0.1 to 5.8 ± 0.3 cm/year at 6 and 12 months, and maintained at 4.8 ± 0.3 cm/year by two years (all P<0.001). Girls who were younger and whose bone age was delayed grew faster (P<0.001). Oxandrolone dose correlated with height velocity at 12 (r= 0.39, P<0.05) and 18 months (r= 0.31, P<0.05). Both height standard deviation score (SDS) and estimated mature height (EMH) increased significantly by the end of treatment (-0.31 ± 0.2, and to 0.45 ± 0.2, and 140.4 ± 1.1 cm to 144.4 ± 1.1 cm respectively (both P<0.0001). in 23 patients who had completed growth at a mean age of 20.6 ± 0.83 years, final height was 145.5 ± 1.3 cm. This was not significantly different from EMH of 144.9 ± 1.3 cm at the end of therapy, and based on a pre-treatment EMH of 140.5 ± 1.3 cm, represented a mean height gain of 5 cm. Furthermore, based on height SDS for Turner syndrome at age 18 of 0.2 ± 0.2, compared with pre-treatment height SDS of -0.32 ± 0.2, there was an increased SDS by the end of therapy of 0.5, equivalent to 4–5 cm. Side effects of oxandrolone were minor and infrequent, limited to increased muscularity and some degree of voice deepening. It is concluded that in Turner syndrome use of the anabolic steroid oxandrolone: (i) increases height velocity for up to 2 years of treatment; (ii) increases final height by 4–5 cm, based on both bone age EMH prediction and use of height standard deviation scores; (iii) is associated with reliable prediction of final height at end of therapy using Greulich-Pyle/ayley-Pinneau methods. Oxandrolone is an effective, economic, safe and well-tolerated promoter of growth in Turner syndrome.     

Growth hormone therapy for 3 years: The OZGROW experience

Objective : To examine the growth response over 3 years of growth hormone deficient (GHD) and non-GHD children who have received growth hormone (GH) in Australia.
Methodology : A retrospective study of a group of patients (1362 children) who commenced GH prior to 1 September 1990. Data were collected at 12 growth centres located in major cities throughout Australia. The data were transferred after informed consent to the national OZGROW database located at the Royal Alexandra Hospital for Children, Sydney, NSW. Of the 1362 children, 898 had received 3 years or more GH therapy and were eligible for this analysis. This cohort was then categorized by diagnosis. Growth response was assessed using height standard deviation score, estimated mature height, growth velocity (GV), GH dose and bone age (years).
Results : For children who completed 3 years therapy, the baseline characteristics among diagnostic groups were similar with mean height standard deviation score (SDS) less than – 3 SDS (except for the malignancy group) and mean GV ranging from 3.5 to 4.4 cm/year. The GV during the first year improved in all groups (7.7-9.4 cm/year) followed by an attenuated response during the second and third years of therapy. After 3 years GH therapy the GHD group with peak levels <10 mU/L demonstrated the greatest change in estimated mature height and height SDS. The GHD group with peak levels between £10 but <20 mU/L had a growth response similar to the non-GHD children for all outcome parameters. Change in bone age ranged from 3.1 to 3.8 years with no differences being noted between the diagnostic groups, nor consistently with pubertal status.
Conclusions : Australian GH guidelines have targeted very short children when compared to other series. This large cohort of non-GHD children has demonstrated short-term benefits of GH therapy; however, the long-term benefit remains unclear until these children reach final adult height.     

Changes with growth hormone treatment in growth hormone deficient children

A total of 54 previously untreated patients (15 girls, 39 boys) with poor growth due to idiopathic growth hormone deficiency (IGHD) were treated with human growth hormone (hGH), continuously up to 4 years. All of the patients had a peak hGH level which was below 10 ng/mL after at least two pharmacological tests and/or blunted physiologic hGH secretion, and their height was below ?2.5 s.d. for age and gender. After the 1st year of therapy, height velocity (HV) increased significantly when compared with baseline (from 3.18 ±0.76 cm/year to 9.17±1.03 cm/year; P <0.001), declined during the 2nd year and then remained significantly higher than pretreatment HV. When considering improvement in height expressed by height standard deviation score (SDS), during the therapy all of the patients showed a significant gain ± 1.72±1.09 (from ?4.11±0.61 to ?2.21±0.48). The height values were significantly higher than pretreatment, but remained below ?2 s.d. after 4 years of hGH therapy in our patients. Increased height velocity has been sustained, but height improvement after therapy was inversely correlated to height SDS for chronological age of patients at the start of therapy. In conclusion post-treatment height has been shown to be related to height deficit at the beginning of therapy. Therapy was well tolerated with no local or systemic adverse effects or acceleration of bone age.     

Impact of growth hormone treatment on a Belgian population of short children with renal allografts

We retrospectively analyzed the effects of recombinant human growth hormone (rhGH) in a Belgian population of 36 short children with renal allografts. Seven children were dropped from the growth study: 1 had skeletal dysplasia and in 6 cases rhGH was given for less than 1 yr (1 died, 1 developed genu valgum, 2 were non-compliant and 2 grafts deteriorated). Final height was reached in 17 patients, and 12 children were still growing at the end of the study. Median height standard deviation score (SDS) in the 29 patients was -2.3 at the time of transplantation, and -2.7 when rhGH therapy was initiated. During rhGH therapy (median duration 3.2 yr, range 0.6-7.7 yr), height SDS increased by a mean of 0.4 per year, and bone maturation was not accelerated. Final height reached was 162.7 (149.0-169.5) cm (median SDS -1.8) in males and 151.0 (130.5-169.5) cm (median SDS -1.9) in females. Final height is significantly greater in males than females compared with a historical control group of untreated patients. Final height is within the parental target height range in 6 out of the 17 patients. The increase in height SDS in patients who were at an advanced stage of puberty (Tanner stages 4-5) when rhGH therapy was initiated exceeded our expectations (mean height gain 14.2 cm in boys and 10 cm in girls). In the cohort of 36 children, 4 patients developed an acute allograft rejection, all of whom had an underlying chronic rejection. This resulted in 3 graft losses within 5 yr. Our results indicate that rhGH treatment has a positive effect in short children with renal allografts, even if it is started in late puberty. In the presence of underlying chronic rejection, rhGH treatment needs careful monitoring to minimize the risk of graft loss.     

Multicentric study of efficacy and safety of growth hormone use in growth hormone deficient children in India

Growth Hormone being very expensive in India data on use of recombinant human growth hormone (rhGH) is scarce. The authors studied the effect and safety of one year of therapy with rhGH on growth velocity and predicted final height in Indian patients with growth hormone deficiency (GHD). A multicentric, prospective, open trial with rhGH was performed on 15 patients. Patients received rhGH in a dose of 0.7 IU (0.23 mg)/Kg/week. The mean pretreatment height was 111.2cms {SD 12.4}, height velocity was 3.1 cms per year {1.2} and predicted height was 146.5 cms {10.4} at a mean age of 12.0 (2.8). At the end of therapy mean height was 123.4 {11.9}, height velocity was 12.1 cms per year {2.8} and the predicted height was 153.0 cm {9.4}. The increase in predicted height was thus 6.5cm (4.2). The increment in height velocity with growth hormone therapy was statistically significant (p value= 0.001). The present study shows that children with growth hormone deficiency in India also benefit from therapy with rhGH even when treatment is started late as compared to the published Western data and there is a potential for increased final height.     

GnRHa治疗中枢性性早熟女童对终身高的影响

目的：观察促性腺激素释放激素类似物（GnRHa）对治疗中枢性性早熟（central precocious puberty,CPP）女童终身高的作用及相关因素。方法：对26例CPP女童应用GnRHa治疗前后预测身高、骨龄的标准差分值［HtSDS(BA)］、终身高、体重指数（BMI）、初潮情况等进行评价,分析它们与终身高的相关性。结果：治疗前预测身高为151.5±5.7 cm;停药时预测身高为158.4±5.2 cm;终身高为158.0±4.0 cm,高于靶身高155.3±4.4 cm (P<0.01)。终身高与初始身高、预测身高、HtSDS(BA)正相关。治疗前BMI为17.1±2.1、治疗后BMI为19.9±3.2,两者呈正相关。停药后平均13.2±6.1个月后初潮,平均初潮年龄为12.2±0.7岁。结论：GnRHa治疗CPP可有效地改善终身高,终身高与治疗前身高及预测身高等密切相关,停药后患儿青春发育与正常儿童相似。［中国当代儿科杂志,2009,11（5）：374-376］