儿童肾病综合征相关生长迟缓及防治进展

肾病综合征(nephrotic syndrome,NS)是儿童常见的肾脏疾病.糖皮质激素(glucocorticoids,GC)作为NS治疗一线用药,可通过多种途径引起生长激素(growth hormone,GH)分泌和合成障碍,使GH水平降低从而影响生长发育.肾病本身可干预胰岛素样生长因子及胰岛素样生长因子结合蛋白的分泌和调节,生长激素-胰岛素样生长因子轴发生变化是NS患儿生长迟缓的原因之一.NS患儿骨代谢异常和甲状腺功能低下也影响其生长发育.该文对NS相关生长迟缓及其防治作一综述.     

矮小儿童的生长激素-胰岛素样生长因子轴功能的检查

生长激素-胰岛素样生长因子(GH-IGF-1)功能轴的异常是引起儿童身材矮小的重要原因。根据病因可将其分为3类：具有生物活性的生长激素(growth hormone,GH)分泌不足;胰岛素样生长因子(insulin-like growth factors,IGFs)产生减少;外周组织对IGFs产生抵抗。早期明确诊断并应用基因重组人生长激素(rhGH)治疗可以有效地提高最终成人期身高。为了在临床上正确使用rhGH,     

肠道炎症阻滞儿童体格生长的免疫和内分泌机制

肠道炎症常伴发儿童的生长落后。生长激素(GH)和胰岛素生长因子-1(IGF-1)是调控出生后骨骼纵向生长的重要物质,抑制GH/IGF轴可阻滞儿童体格生长。肠道发生炎症时,异常升高的促炎症因子IL-1β、IL-6和TNF-α通过干扰GH/IGF轴,系统性以及在生长板局部水平影响骨骼生长,进而导致儿童生长阻滞。     

生长激素-胰岛素样生长因子Ⅰ轴对儿童生长和代谢的调控

儿童生长主要受生长激素（GH）胰岛素样生长因子I（IGF－I）轴调控。GH刺激外周组织尤其是肝脏分泌IGF－I，后者介导了GH促生长的主要功能，GH亦直接作用于靶细胞发挥促生长及调节代谢的作用。近年研究发现胰岛样生长因子结合蛋白（IGFBP）对IGF－I起重要调节作用，并对GH－IGF－I轴调控的作用模式提出了新的见解。     

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。     

胰岛素样生长因子-1受体基因与特发性矮小相关性研究进展

生长激素-胰岛素样生长因子(GH-IGF)轴是调节儿童生长发育中最重要的神经内分泌轴.胰岛素样生长因子-1受体( IGF-1 R)是调节该轴的激素受体级联反应的效应分子,它的分子结构或功能异常,将影响靶基因IGF-1与其结合,从而引起生长障碍,可能与特发性矮小(ISS)发生有一定关系.国内外尚无IGF-1R基因与ISS的研究,为探讨其与ISS的关系,现就近年来有关IGF-1 R与人体生长障碍的研究作简要综述.     

特发性矮小患儿生长激素-胰岛素样生长因子轴变化的研究

目的 观察特发性矮小(ISS)患儿血中生长激素(GH)、胰岛素样生长因子-l(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)及生长激素结合蛋白(GHBP)水平的变化.方法 2002年6月至2006年5月在中南大学湘雅二医院儿科就诊的37例ISS患儿为病例组,37例年龄性别相匹配的正常儿童为对照组.采用放射免疫分析法(RIA)测定血清GH,免疫放射计量法(IRMA)测定血清IGF-1及IGFBP-3,葡聚糖覆盖炭末吸附法(DCT)检测血清GHBP.结果 ISS组血清GHBP、IGF-1、IGFBP-3均明显低于对照组(均P＜0.01),而血清GH基础值在ISS组明显高于时照组(P＜0.05).结论 ISS患儿血中IGF-1和IGFBP-3降低可能是其矮小的原因之一.ISS患儿血中反映生长激素受体(GHR)水平的GHBP降低,而GH基础值升高,提示可能存在因GHR缺陷导致的GH不敏感.     

胎儿生长中Ghrelin与其他内分泌因子的关系

Ghrelin是生长激素促分泌物质受体的内源性配体,含28个氨基酸残基的小分子多肽,为体内发现的第3个调节生长激素(GH)释放的激素[1],能有效促进GH分泌,调节机体进食和能量平衡,还与其他激素分泌有着密切的关系.Ghrelin可能是生长激素/胰岛素样生长因子1轴和调节能量平衡的神经内分泌之间新的联结纽带[2].通过免疫组织化学技术,从人类怀孕10周至足月均可在胎盘内检测到Ghrelin,说明Ghrelin对促进胎儿生长起积极作用.本研究通过检测正常适于胎龄儿Ghrelin、GH、胰岛素样生长因子-1(IGF-1)和胰岛素(INS)的水平,探讨它们之间的关系.     

GH／IGF—1轴对肾脏的影响

生长激素（GH）/胰岛素样生长因子（IGF）-1轴由GH、IGF-1、GH受体、IGF-1受体、GH结合蛋白、IGF结合蛋白组成。除GH外,其余各成分在肾脏中都有表达并有各自特定的分布。对肾小管重吸收功能及肾小球血液动力学有影响,并与肾脏疾病,尤其是肾小球硬化的发生、发展有关。本文就GH/IGF-1轴对肾脏在生理和病理状态下的影响进行综述。     

胰岛素抵抗和儿童生长

胰岛素抵抗(IR)是指胰岛素分泌能力正常,但因其信号转导环节的障碍,致使不能发挥其生物效应,高胰岛素血症足IR的重要特征.IR是代谢综合征(Ms)的核心,儿童IR除了是Ms的风险因素外,近年发现它还与生长有密切关系.生长是儿童特有的生理现象,它涉及以促牛长素轴激素为主体的多种内分泌激素对生长和代谢的双重调控.促生长素轴是以生长激素(GH)为核心的生长调控轴,GH直接和间接地经胰岛素样生长因子1(IGF-1)实现其促生长作用.     

儿童生长与生长障碍

生长是反映儿童健康状况、营养和遗传背景的敏感指标。身高和身高生长速度偏离正常范围可能预示着某种潜在先天性或获得性疾病。所幸的是，绝大多数被生长困扰儿童并没有明显的生长异常。然而，只有对正常生长过程有充分认识，且掌握正确生长评价方法，才可能识别真正生长障碍、发现早期的生长偏离；才能给那些生长变异的儿童以合理咨询、指导和正确治疗。     

Growth and Growth Hormone Therapy in Hypochondroplasia

ABSTRACT. The growth of 84 patients with hypochondroplasia (56 male, 28 female) was studied. A wide spectrum of severity was found from quite severe short limbed dwarfism to short apparently normal prepubertal children who manifested disproportion only at puberty when growth failed. The onset of puberty was at the normal time but the pubertal growth spurt appeared not to materialize and it is this lack which resulted in severely compromised adult heights of 145-165 cm in boys and 133–151 cm in girls. Twenty (12 M, 8 F) hypochondroplastic children aged between 4.3 and 12.8 years were recruited to a study of the effects of biosynthetic growth hormone. All had normal growth hormone responses (> 15 mU/I) to a pharmacological test of growth hormone secretion. Biosynthetic growth hormone in doses between 12-32 u/m²/week produced a significant acceleration in height velocity standard deviation score (SDS) for chronological age (CA) from a pretreatment mean of - 1.66 (SD 1.36) to + 1.62 (SD 1.52) ( p < 0.001). Significant increases were also observed in the height SDS for bone age (BA), sitting height (SH) SDS and subischial leg length (SILL) SDS. A longer period will be required to assess the effect of treatment on adult height prognosis.     

Growth Hormone Secretion and Growth Hormone Treatment in Children with Intrauterine Growth Retardation

Albertsson-Wikland, K. (Departments of Paediatrics II and Physiology, University of Gothenburg, Gothenburg, Sweden). Growth hormone secretion and growth hormone treatment in children with intrauterine growth retardation. Acta Paediatr Scand [Suppl] 349: 35, 1989.
Few children with intrauterine growth retardation (IUGR) fail to show catch-up growth during the first year of life. There may he many reasons for this, ranging from disturbances of hormone production to hormonal unresponsiveness of target cells. This report presents preliminary data on growth hormone (GH) secretion and responses to GH treatment in 16 children with IUGR and poor catch-up growth, six of whom had Silver-Russell stigmata. GH secretion was assessed by measurement of the GH response to an arginine-insulin test and determination of spontaneous GH secretion over 24 hours. GH production was heterogeneous hut, more often than expected, children showed both a low response to GH provocation and low spontaneous secretion of GH. Five out of six of the children with Silver-Russell syndrome and seven out of 10 of the children with non-Silver-Russell IUGR gained more than 2 cm in height during 1 year of treatment with GH at a dose of 0.1 IU/kg/day. These results clearly demonstrate that some children with IUGR and poor catch-up growth secrete insufficient amounts of GH, and that many of these very short children show an improvement in growth rate during treatment with physiological doses of GH.