生长激素缺乏症患儿血清胰岛素样生长因子-1及其结合蛋白的变化

目的 研究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)浓度与生长激素缺乏症(GHD)患儿生长激素(GH)激发试验中血清GH峰值关系,为其代替GH激发试验提供依据。方法选择GHD患儿62例(男39例,女23例),为GHD组;60例健康儿童(男38例,女22例)为对照组。分别用放射免疫分析法(RIA)、免疫放射分析法(IRMA)检测两组血清IGF-1、IGFBP-3浓度,同时做GH激发试验,测定血清GH峰值,并比较其与IGF-1、IGFBP-3的关系。结果 GHD血清IGF-1、IGFBP-3均显著低于对照组(t=3.116、11.579 P均<0.01);GHD组血清IGF-1、IGFBP-3浓度与GH激发试验中GH峰值呈显著正相关(r=0.331、0.347 P均<0.01);GHD组血清IGF-1、IGFBP-3降低阳性率分别为97.58％、98.38％,与激发试验的阳性率(100％)比较无统计学意义(x~2=3.074、2.033 P均>0.05)。结论 血清IGF-1、IGFBP-3浓度的检测对诊断GHD有重要意义;检测血清IGF-1、IGFBP-3浓度可替代GH激发试验。     

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。     

血清胰岛素样生长因子-1、胰岛素样生长因子结合蛋白-3在矮小症儿童诊断和疗效判断中的价值

目的探讨胰岛素样生长因子-1（IGF-1）及其结合蛋白-3（IGFBP-3）在矮小症儿童诊断及疗效判断中的价值。方法1．对124例青春发育前矮小症患儿用精氨酸激发试验和可乐定激发试验检测其血清生长激素（GH）水平，并根据患儿GH峰值分为生长激素缺乏组（GHD组，40例）、特发性矮小组（1SS组，84例）。选取20例健康儿童作为健康对照组。对所有儿童采用酶联免疫吸附法检测血清IGF—1和IGFBP-3。对GHD组、ISS组和健康对照组儿童血清IGF-1和IGFBP-3水平进行两两比较。2．对15例GHD和30例ISS患儿予国产重组人生长激素（rhGH）0．1IU／（kg&#183;d）治疗6个月，于治疗前及治疗6个月分别测定其身高、体质量、骨龄及血清IGF-1、IGFBP-3，并进行治疗前后的对照。结果1．GHD组和ISS组患儿血清IGF-1和IGFBP-3水平明显低于健康对照组（Pa〈0．01），GHD组与ISS组患儿血清IGF-1和IGFBP-3水平比较均有显著差异（Pa〈0．01），GHD组患儿治疗前后血清IGF-1、IGFBP-3比较有显著差异（Pa〈0．01）；诊断GHD，IGF-1的特异性为67．8％，敏感性为75％；IGFBP-3的特异性为88％，敏感性为85％。2．rhGH治疗后身高增长速度明显加快，血清IGF-1、IGFBP-3水平显著升高；治疗前血清IGF-1与治疗6个月生长速度呈显著负相关（r=-0．78P〈0．01）；治疗6个月后IGF-1的变化与治疗后生长速度呈显著正相关（r=0．82P〈0．01）。结论IGF-1、IGFBP-3可用于儿童矮小症的诊断及疗效评价。     

重组人生长激素对38例特纳综合征的疗效观察

目的探讨重组人生长激素(rhGH)治疗特纳综合征(TS)的疗效及影响疗效的因素。方法选取确诊为TS的患儿38例为研究对象,每晚均接受rhGH治疗,剂量0.11～0.21 IU.kg-1.d-1,疗程6～36个月。定期随访,观察生长速率(GV)、胰岛素样生长因子-1(IGF-1)和甲状腺功能、肝功能、糖化血红蛋白等。按照rhGH用药剂量将患儿分为2组,≤0.15 IU.kg-1.d-1组和>0.15 IU.kg-1.d-1组,分析不同剂量与疗效的关系。按照治疗初始年龄将患儿分成≤10岁组及>10岁组,分析治疗年龄与疗效的关系。按照治疗前生长激素(GH)峰值将患儿分成GH≥10μg.L-1组及<10μg.L-1组,观察疗效与治疗前GH峰值的关系。结果 TS患儿用药前及用药0.5 a后GV[(2.47±0.42)cm.a-1vs(9.37±2.68)cm.a-1]比较差异有统计学意义(P=0.001)。IGF-1由用药前(186.73±73.32)μg.L-1增至用药后0.5 a(433.93±163.91)μg.L-1,二者比较差异有统计学意义(P<0.001)。rhGH剂量与GV无显著相关。治疗初始年龄与第1年GV无关。治疗前GH峰值与GV无显著相关。结论 rhGH治疗TS可以明确改善身高。较以往常用剂量更小的剂量也可以达到很好的疗效。用药前患儿GH峰值与疗效关系不大,可以不用常规做GH激发试验。患儿治疗的初始年龄与GV无明显相关性。IGF-1是治疗过程中的重要检测指标。     

重组人生长激素治疗不同垂体发育状况生长激素缺乏症患儿疗效的前瞻性研究北大核心CSCD

目的探讨重组人生长激素(recombinant human growth hormone,rhGH)对不同垂体发育状况生长激素缺乏症(growth hormone deficiency,GHD)患儿的治疗效果。方法前瞻性选取2020年6月—2021年12月许昌市妇幼保健院收治的90例GHD患儿为研究对象,根据垂体正中矢状高径将患儿分为垂体发育不良组(45例)、垂体正常组(31例)、垂体发育增大组(14例)。分析比较各组身高、生长速率、身高标准差分值、血清胰岛素样生长因子结合蛋白-3、胰岛素样生长因子-1,以及治疗前后上述指标变化的差值(差值用△表示)。结果治疗后3组身高、生长速率、身高标准差分值及血清胰岛素样生长因子结合蛋白-3、胰岛素样生长因子-1水平均高于治疗前(P<0.05);垂体发育不良组、垂体发育增大组△身高、△生长速率、△身高标准差分值、△胰岛素样生长因子-1、△胰岛素样生长因子结合蛋白-3均大于垂体正常组(P<0.05);3组不良反应发生率比较差异无统计学意义(P>0.05)。结论rhGH治疗不同垂体发育的GHD患儿均有促进骨生长、增加身高的作用,对垂体发育不良及增生患儿效果更明显,且安全性可靠。     

生长激素缺乏儿童血清胰岛素样生长因子-1和瘦素水平的变化及其相互关系

目的探讨生长激素缺乏(GHD)儿童血清胰岛素样生长因子1(IGF1)、瘦素水平的变化。方法用放射免疫法分别检测20例正常青春期前儿童和23例GHD患儿血清IGF1和瘦素的水平。结果GHD组血清IGF1水平(51.158±29.988)μg/L低于对照组(112.680±41.540)μg/L,两者有显著差异(t=5.619P<0.01);瘦素水平(6.002±2.204)μg/L高于对照组(4.523±2.204)μg/L,两者比较有显著差异(t=2.225P<0.05);但IGF1和瘦素之间无相关性(P>0.05)。结论IGF1和瘦素对GHD患儿生长发育的调节作用是相互独立的。     

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…     

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目的探讨血清生长激素(GH)、胰岛素样生长因子-1(IGF-1)及尿GH检测对矮小儿童诊断的意义。方法华中科技大学同济医院儿科于2004-11—2005-06对106例矮小儿童进行垂体功能复合刺激试验,试验前收集所有受试者夜间12h(2000~800)尿。另选取19例正常青春发育期前儿童为对照组。对垂体功能复合刺激试验GH分泌异常的56例矮小儿童,用ELISA方法检测相应的血清GH、IGF-1及尿中GH水平,并进行相关分析。结果根据垂体功能复合刺激试验的GH检测结果将矮小儿分类,包括完全性GH缺乏症(cGHD)25例、部分性GH缺乏症(pGHD)9例和GH神经分泌功能障碍(GHND)22例。GHD组患儿血清IGF-1、尿GH水平与正常儿相比明显降低(P<0·01)。pGHD和GHND组患儿血IGF-1水平波动较大,无统计学差异。GHND组患儿尿GH水平按ng/g肌酐(Cr)计量显著低于正常对照相(P<0·05),而按ng/12h尿量计算值虽低于正常组,但无统计学意义(P>0·05)。pGHD组患儿尿GH水平按两种方法计量值均介于正常和GHD患者之间,与正常及GHD患者比较均有显著性差异(P均<0·05)。cGHD和pGHD组患儿尿GH的ng/gCr计量值与其血GH峰值呈显著性正相关(rcGHD=0·556,P<0·05;rpGHD=0·423,P<0·05),GHND组患儿尿GH的ng/gCr计量值与其血中GH峰值无相关性(P>0·05)。结论尿GH水平测定无创、简便,配合IGF-1等指标的检测,对于矮小儿童的诊断和鉴别诊断具有重要意义。     

血清胰岛素浓度的变化与肥胖儿童生长关系的探讨

目的探讨单纯性肥胖儿童的生长与其血清胰岛素(Ins)、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)浓度的关系。 方法2004 03中山大学附属二院对31例单纯性肥胖儿童及48例同龄正常儿童的生长参数及空腹Ins、IGF 1、IGFBP 3浓度进行测定,并进行比较及相关性分析。 结果肥胖组血清Ins、IGFBP 3浓度显著高于对照组(P<005,P<001),而两组间IGF 1差异则无显著性意义,血清Ins浓度与BMI、IGFBP 3呈正相关,肥胖儿童身高SDS与1NS、IGF 1正相关。 结论肥胖儿童存在有非生长激素(GH)依赖性生长的代偿机制。其中高胰岛素血症可能参与了这一过程,它既可以通过增加IGFBP 3的合成来间接提高IGF 1的生物活性,又可以直接发挥促生长作用。     

矮小儿童下丘脑-垂体及其胰岛素样生长因子轴功能检查的意义

目的检测矮小儿童下丘脑-垂体及其胰岛素样生长因子(IGF-1)生长轴(GHRH-GH-IGF-1)功能,了解矮小儿童的发病因素及确定下丘脑-垂体及其IGF轴功能缺陷病因分类。方法矮小儿童30例。用统一印制的矮小儿童表格记录其临床特征。对矮小儿童进行甲状腺功能测定;用胰岛素 左旋多巴行生长激素(GH)刺激试验;放射免疫法测定血清IGF-1和血清胰岛素样生长因子结合蛋白-3(IGFBP-3)水平;同时行患儿骨龄、垂体增强MRI扫描、染色体核型分析、性激素测定。根据矮小症诊断标准和2004年Rosenfeld RG和GHRH-GH-IGF-1轴缺陷不同,将矮小儿童进行病因定位和分类。结果矮小儿童30例中,下丘脑-垂体及其IGF轴功能缺陷12例,占40%,其中肯定生长激素缺乏(GHD)4例,怀疑生长激素不敏感综合征2例,可疑GHD 6例。Turner′s综合征2例,占6.67%;体质性青春期延迟2例,占6.67%;特发性矮小14例,占46.6%。磁共振发现垂体微腺瘤2例;垂体发育不良12例。结论1.矮小儿童所占比例最大的为特发性矮小,其次为下丘脑-垂体及其IGF轴功能缺陷。2.IGF-1水平和IGFBP-3水平与生长激素刺激试验测定生长激素水平不一致,考虑存在生长激素抵抗和受体缺陷。3.矮小儿童可能存在先天性垂体发育异常,致使垂体分泌生长激素不足。     

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生长迟缓是儿科较常见的症状,矮小是其主要表现,一般认为身高年增长速率低于5cm者为生长迟缓。其病因复杂,临床各具特征,分类方式也不完全统一。本文将就生长评估方法及生长迟缓的病因分类作一阐述。1生长决定因素近年认为生长发育尤其是身高决定于三大因素:(1)生物学因素(遗传、内分泌、宫内外疾病、致畸因子及有害物质接触和营养);(2)心理因素(气质、行为、情绪等影响进食行为和神经内分泌调节);(3)社会因素(食物品种、进食习俗及其对发育的影响)。2生长评估方法生长评估包括人体测量学指标以及常用的辅助诊断手段(以骨龄为主)。2.1身高、…     

生长激素及胰岛素样生长因子-Ⅰ对新生儿生长发育调控的观察

目的　探讨生长激素 (GH)、胰岛素样生长因子 Ⅰ (IGF Ⅰ )在新生儿期的变化及对新生儿体格发育的影响。方法　 5 6例新生儿分成 3组 :A组 (18例 )为早产适于胎龄儿 ;B组 (18例 )为早产小于胎龄儿 ;C组 (2 0例 )为足月适于胎龄儿。各组新生儿按生理需要量满足营养供给 ,分别在生后 3d内、30d时抽取股静脉血检测血GH、IGF Ⅰ水平及血糖值。结果　出生时血IGF Ⅰ水平足月儿大于早产儿 ,早产适于胎龄儿大于早产小于胎龄儿 ,3组间比较均有非常显著性差异 (P均 <0 0 0 1) ,血IGF Ⅰ值与出生体重及胎龄均呈正相关 (P分别 <0 0 0 1,<0 0 1) ;血GH值早产儿略大于足月儿 ,3组间比较无显著性差异 ,GH值与出生体重、胎龄均无相关性(P均 >0 .0 5 )。至生后 30d时血IGF Ⅰ值各组均较出生时明显增加 (P均 <0 0 0 1) ,血IGF Ⅰ的增长值与体重的增长值呈正相关 (P <0 0 1) ;GH值较出生时稍下降 ,差别无统计学意义。出生时血IGF Ⅰ与GH无相关性(P >0 0 5 ) ,30d时血IGF Ⅰ与GH弱相关 (P <0 .0 5 )。各组新生儿抽血同期血糖值均在正常范围。结论　IGF Ⅰ是胎儿发育的主要调控因子 ,也是新生儿期发育的主要调控激素。至生后 30d时 ,GH IGF Ⅰ轴的调控已基本形成。     

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生长激素缺乏症(GHD)是儿童生长迟缓(矮身材)的常见病因,1956年首次从人垂体中成功分离及提纯了人垂体生长激素(phGH),成为GH研究的标志性进展。1958年phGH用于治疗首例GHD患儿并成功地获得促生长疗效。但是,于1962~1985年3000例接受过phGH治疗的患儿中150例不幸染上Creutzfeldt-Jakob病(CJD)———致命性的脑炎。其原因归咎于垂体抽提过程中被朊病毒(prion)污染,而非GH本身。1985年phGH被禁止应用。同年,无CJD危险的基因重组人生长激素(rhGH)被美国FDA批准用于GHD治疗。rhGH是应用重组DNA技术,于1979年首次成功地使人生长…     

Fetal growth regulation and intrauterine growth retardation

Gestational age and neonatal anthropometric parameters are currently used to evaluate fetal growth and are predictive factors of perinatal and postnatal morbidity and mortality. We performed a retrospective analysis of neonatal anthropometric parameters (weight, vertex-heel length and head circumference) in 1,470 live preterm neonates born between 1997 and 2002 and a prospective analysis of the same parameters in 1,786 live newborns of both sexes born in 2001 and 2002, products of single 37-42 week uncomplicated pregnancies in healthy Spanish Caucasian mothers. A progressive increase in these parameters with gestational age and sexual dimorphism were observed from the 30th week of gestational age onwards, with statistically-significant differences (p<0.05) at 38-42 weeks of gestational age. An increase in weight and length values in relation to previous Spanish studies was also documented in preterm newborns. It is estimated that 10-15% of children born small for gestational age (SGA) do not experience catch-up growth by the age of 3 years and may have short stature in adulthood. Preliminary data of a cross-sectional study on spontaneous growth in boys and girls born SGA without postnatal catch-up growth show that their +2 SD values of height are similar to -2 SD values of our normal control population of children born with adequate weight and length for gestational age (AGE). However, weight +2 SD values are similar to mean values of control children born AGE. In summary, our data show sexual dimorphism in neonatal anthropometric growth parameters and that these parameters change with time and may be updated. In addition children born SGA without postnatal catch-up are shorter and have higher weight than age-, height- and sex-matched controls born AGE.     

Comparison of growth hormone releasing hormone therapy and growth hormone therapy in growth hormone deficiency

Seven children with growth hormone deficiency of hypothalamic origin responded to an i.v. bolus of growth hormone releasing hormone (GHRH) (1–29)-NH2 with a mean serum increase of 10.7 ng/ml growth hormone (GH) (range 2.5–29.3 ng/ml). Continuous s.c. administration of GHRH of 4–6 g/kg twice daily for at least 6 months did not improve the growth rate in five of the patients. One patient increased his growth rate from 1.9 to 3.8 cm/year and another from 3.5 to 8.2 cm/year; however, the growth rate of the latter patient then decreased to 5.4 cm/year. When treatment was changed to recombinant human growth hormone (rhGH) in a dose of 2 U/m² daily, given s.c. at bedtime, the growth rate improved in all patients to a mean of 8.5 cm/year (range: 6.2 to 14.6). Presently GHRH cannot be recommended for the routine therapy of children with growth hormone deficiency since a single daily dose of rhGH produced catch-up growth which GHRH therapy did not.Abbreviations GH growth hormone - GHD growth hormone deficiency - GHRH growth hormone releasing hormone - hGH human growth hormone - rhGH recombinant human growth hormone - SM C/IGF I somatomedin C/insulin-like growth factor I On the occasion of the 85th birthday of Prof. Dr.Dr.h.c. mult. Adolf Butenandt     

Insulin like growth factors axis and growth disorders

The growth hormone-insulin like growth factor (GH-IGF) axis plays a crucial role in the regulation of growth. Initially considered to be a mediator of growth hormone actions, IGF axis has been established as an independent endocrine system with wide array of actions. Recent advances have led to tremendous increase in the clinical utility of the IGF axis. IGF-based investigations (IGF1 and IGF binding protein 3) are now replacing GH-based investigations for evaluation and monitoring of disorders of the GH-IGF axis. IGF therapy has been successfully utilized in growth hormone insensitivity syndrome and GHD type 1B. The possibility of IGF axis as therapeutic options is being explored in wide variety of disorders like hypoxic-ischemic encephalopathy, Alzheimer's disease and psoriasis.     

X-linked agammaglobulinemia, growth hormone deficiency and delay of growth and puberty

Buzi F, Notarangelo LD, Plebani A, Duse M, Parolini O, Monteleone M, Ugazio AG. X-linked agammaglobulinemia, growth hormone deficiency and delay of growth and puberty. Acta Paediatr 1994;83:99–102. Stockholm. ISSN 0803–5253
Coinheritance of X-linked agammaglobulinemia and growth hormone deficiency (XLA/GHD) has been classified as an independent primary immune deficiency. We evaluated the pattern of growth and endocrine function in seven XLA subjects (ages 10.9–20.1 years); four belonged to two different XLA pedigrees and three represented sporadic XLA cases. Three had reached adulthood (final stature 176.0, 173.5 and 165.0 cm, respectively) and their retrospective growth showed delay in growth and puberty during adolescence. In the other four subjects, growth hormone production was measured by growth hormone pharmacological stimulation tests (clonidine, arginine): three of four patients had insufficient growth hormone responses (peak growth hormone < 10 μg/l); all three had delayed puberty; their growth hormone responses increased after "priming" with testosterone, reaching values > 10 μg/l in two of them and allowing diagnosis of "true" growth hormone deficiency in the third. The fourth was a normally growing subject who showed a normal growth hormone response both before and after testosterone priming. Six out of the seven subjects showed a growth pattern consistent with delay in growth and puberty. Our results suggest that true XLA/GHD is rarer than previously supposed and that subnormal responses to growth hormone stimulation tests may be found without sex steroid priming of the test in adolescence. The most probable growth pattern in XLA appears to be delay in growth and puberty, as has already been described for other chronic diseases.