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.     

矮小儿童血浆ghrelin及GHBP变化及其与生长的关系

目的 检测矮小儿童血浆ghrelin及生长激素结合蛋白(GHBP)水平变化,探讨其在矮小儿童生长发育中的作用.方法 收集就诊的矮小儿童70例,根据生长激素刺激试验GH峰值<7 ng/ml、7～10ng/ml、>10ng/ml分为生长激素缺乏组1(GHD 1,加例)、生长激素缺乏组2(GHD 2,20例)及特发性矮小组(ISS,30例);抽取20例年龄、性别相匹配的正常身高儿童作为对照组.对其进行全面的病史采集和体格检查,并检测血浆ghrelin及血清GHBP水平.采用方差分析、卡方检验及多元回归分析等统计学方法对结果进行分析.结果 GHD 1组血浆ghrelin水平低于其余三组[(4.21±2.70)ng/ml对(6.12±2.16)ng/ml、(6.20±2.75)ng/ml、 (5.11±2.53)ng/ml,P均<0.05];GHD 2组与ISS组血浆ghrelin水平近似,高于正常对照组[(6.12±2.16)ng/ml、(6.20±2.75)ng/ml对(5.11±2.53)ng/ml,P<0.05)].对ghrelin进行多重线性回归分析得出体重为ghrelin的独立影响因素(β=-188.46,P<0.000 1).GHD 1组血清GHBP水平与正常对照组差异无统计学意义[(3 869.6±702.1)pmol/ml对(4 192.9±1 043.5)pmol/ml,P>0.05)];GHD 2组与ISS组血清GHBP水平近似,均低于正常对照组[(3 584.2±469.5)pmol/ml、(3 443.5±568.4)pmol/ml对(4 192.9±1 043.5)pmol/ml,P<0.05)].结论 血浆ghrelin在不同的矮小症中所扮角色不同,GH峰值<7 ng/ml中为病因之一;而GH峰值>7 ng/ml的矮小症中为对低体质量的适应性代偿.ISS及GHD 2组血清GHBP水平低下,提示这两组中存在生长激素受体(GHR)突变.     

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。     

重组人生长激素治疗对特发性矮小症儿童血清Klotho和成纤维细胞生长因子23的影响北大核心CSCD

目的比较重组人生长激素(recombinant human growth hormone,rhGH)治疗前后特发性矮小症(idiopathic short stature,ISS)患儿血清Klotho、成纤维细胞生长因子23(fibroblast growth factor,FGF23)和胰岛素样生长因子(insulin-like growth factor,IGF)-1水平变化,探讨Klotho和FGF23与ISS患儿生长激素(growth hormone,GH)/IGF-1生长轴的关系。方法前瞻性选择2021年3月10日—2022年12月1日在河北省人民医院儿科确诊为ISS的33例儿童为ISS组,选择同期于儿童保健科就诊,年龄、性别与ISS组匹配的29例健康儿童为健康对照组。ISS组给予rhGH治疗,比较治疗前及治疗3、6、9个月血清Klotho、FGF23、IGF-1水平,并进行相关性分析。结果ISS组与健康对照组的血清IGF-1、Klotho、FGF23水平比较差异无统计学意义(P>0.05)。rhGH治疗3、6、9个月的ISS组血清Klotho、FGF23、IGF-1水平均较治疗前显著升高(均P<0.05)。ISS组治疗前Klotho、FGF23与磷酸盐水平均呈正相关(P<0.05);治疗前及治疗3、6、9个月的Klotho与IGF-1水平均呈正相关(P<0.05),FGF23与IGF-1水平均呈正相关(P<0.05),Klotho与FGF23水平均呈正相关(P<0.05),Klotho、FGF23水平与身高标准差积分无相关性(P>0.05)。结论rhGH治疗可上调Klotho、FGF23及IGF-1水平,实现ISS患儿的追赶生长。Klotho、FGF23可能并非直接促进ISS患儿线性生长,而是可能通过IGF-1及磷酸盐代谢等途径产生间接影响。Klotho、FGF23与IGF-1的一致变化表明三者在调节ISS线性生长中存在协同关系。     

生长激素受体基因异常及多态性与特发性矮小的关系研究进展

随着促生长激素释放激素-生长激素-胰岛素样生长因子(GHRH-GH-IGF-1)轴和基因学研究的深入,生长激素受体基因(GHR基因)的突变及其核苷酸多态性与特发性矮小(ISS)的关系逐渐明了.GHR基因异常多发生在生长激素受体(GHR)蛋白的胞外区,可引起细胞内信号转导障碍,导致GHR蛋白功能及表达部分缺失,生长激素不能完全发挥作用或部分不敏感,从而可能发生ISS; GHR基因单核苷酸多态性(SNP),尤其是外显子Ex3多态性与ISS易感性有关.此外,GHR基因异常及SNP与ISS中IGF-1、生长激素结合蛋白血清水平及重组人生长激素治疗效果密切相关.深入研究ISS中GHR候选基因的筛查、蛋白功能表达及SNP分析,有利于提高ISS的遗传诊断水平,对明确ISS的病因及指导临床治疗具有重要意义.     

人生长激素同型异构体比例变化与特发性矮小症的相关性

人生长激素(human growth hormone,hGH)是出生后促进生长的主要激素,生长激素在调节生长的许多方面都起作用,生长激素缺乏会引起生长激素缺乏性矮小(growth hormone deficiency,GHD),但特发性矮小症患儿(idiopathic short stature,ISS)并不存在生长激素(GH)缺乏[1],其发病机制一直是研究的热点,有研究认为hGH同型异构体(humangrowth hormone isoforms,hGHI)比例的变化可能是ISS的发病机制之一[2,3],hGH有多种同型异构体,在垂体、胎盘和外周血中均存在,各种hGHI单体型的22kDa!hGHI含量最丰富,20kDa!hGHI含量次之,它们在结构上有…     

1496例矮小症病因分析及基于IGF-1水平生长激素缺乏症诊断预测模型的建立

目的探讨矮小症患儿的病因及胰岛素样生长因子(IGF)-1与生长激素(growth hormone,GH)水平之间的关系,建立基于IGF-1水平的简易GH缺乏(GHD)诊断预测模型。方法矮小症住院患儿1 496例,采用胰岛素低血糖法和精氨酸法测定GH分泌状态,根据体格检查及实验室检查分析病因;Logistic逐步多元回归模型建立基于IGF-1的GHD诊断预测模型。结果 GHD659例(44.05%),特发性矮小504例(33.69%),家族性矮小165例(11.03%),体质性青春期发育延迟35例(2.33%),余为甲状腺功能减低症、宫内发育迟缓、Turner综合征、多种垂体激素缺乏症等引起的矮小症。比较GHD与非GHD两组患儿潜在的影响因素,体质量、BMI、身高-SDS、ALT/AST/AKP、TG/Tch、IGF-1、IGFBP-3等的差异有统计学意义(P<0.05)。设GHD的概率为P,经Logistic逐步多元回归模型拟合如下:LN[P/(1-P)]=-2.0193+0.0683×年龄+0.1439×BMI+0.021×ALT-0.0021×IGF-1-0.1526×IGFBP-3。结论内分泌疾病是矮小症最多见的病因,但GH激发试验的水平与多种体格和生化指标有关,因此GHD诊断需要综合考虑;基于IGF-1拟合的简易模型对GHD诊断有较准确的预测价值,可用于门诊筛查。     

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儿童12例

目的　观察重组人生长激素 (rhGH)治疗特发性矮小儿童促生长作用。方法　对 12例特发性矮小儿童使用rhGH治疗 0 .5 7± 0 .18年 ,比较治疗前后年生长速率和预测成年身高结果。结果　经治疗后特发性矮小儿童的年生长速率和预测成年身高有显著提高 ,身高年龄增长明显快于生活年龄和骨龄的增长。结论　rhGH对特发性矮小儿童具有促生长作用     

矮小症的生长激素测定方法及护理

矮小症是指身材低于本民族、本地区健康的和同龄同性别儿童的平均身高2个标准差。严重者称为侏儒症，病因可分为内分泌紊乱，慢性系统疾病、体质性生长及发育延迟、遣传及染色体畸变、骨病、社会心理障碍等。随着近代分子生物研究发展，重组人GH(生长激素)、IGF-1(胰岛素样生长因子)以及合成的GHRH(促生长激素释放激素)、GHRP(生长激素抑制激素)皆已问世，为矮小症尤其GH-IGF     

Pubertal growth and development and prenatal and lactational exposure to polychlorinated biphenyls and dichlorodiphenyl dichloroethene

OBJECTIVES: Polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethene (DDE) are ubiquitous toxic environmental contaminants. Prenatal and early life exposures affect pubertal events in experimental animals. We studied whether prenatal or lactational exposures to background levels of PCBs or DDE were associated with altered pubertal growth and development in humans.Study design: Follow-up of 594 children from an existing North Carolina cohort whose prenatal and lactational exposures had previously been measured. Height, weight, and stage of pubertal development were assessed through annual mail questionnaires. RESULTS: Height of boys at puberty increased with transplacental exposure to DDE, as did weight adjusted for height; adjusted means for those with the highest exposures (maternal concentration 4+ ppm fat) were 6.3 cm taller and 6.9 kg larger than those with the lowest (0 to 1 ppm). There was no effect on the ages at which pubertal stages were attained. Lactational exposures to DDE had no apparent effects; neither did transplacental or lactational exposure to PCBs. Girls with the highest transplacental PCB exposures were heavier for their heights than other girls by 5.4 kg, but differences were significant only if the analysis was restricted to white girls. CONCLUSIONS: Prenatal exposures at background levels may affect body size at puberty.     

Hypokalemia and Hyperkalemia in Infants and Children: Pathophysiology and Treatment

Potassium is the second most abundant cation in the body. About 98% of potassium is intracellular and that is particularly in the skeletal muscle. Electrical disturbances associated with disorders of potassium homeostasis are a function of both the extracellular and intracellular potassium concentrations. Clinical disorders of potassium homeostasis occur with some regularity, especially in hospitalized patients receiving many medications. This article will review the pathophysiology of potassium homeostasis, symptoms, causes, and treatment of hypo- and hyperkalemia.     

Prevention and treatment of overweight and obesity in children and adolescents

Increasing numbers of obese children and adolescents all over the world demand an investment in the primary and secondary prevention of obesity and overweight in this age group. The goal of preventive measures in children is to avoid the negative short- and long-term health problems associated with obesity. Primary prevention aims at establishing a healthy, active lifestyle and keeping children and adolescents within a range of body weight which is considered to be healthy. Constant availability and affordability of palatable and energy-dense food in the affluent society of the western world demands preventive strategies. Universal or public health prevention seems to be the most suitable form because several other cofactors of morbidity and mortality of affluent societies can also be prevented. However, in most European countries there is a lack of awareness of the necessity of prevention programmes, not only among the general population but also among the medical society. More awareness and consciousness to the problem of obesity must be generated in order to lead to effective therapeutic programmes. For those children and adolescents who are already obese, secondary prevention is mandatory. Therapeutic intervention programmes for the obese aim at long-term weight maintenance and normalisation of body weight and body fat. They have to modify eating and exercise behaviour of the obese child and establish new, healthier behaviour and lifestyle. Treatments programmes must include behavioural components in order to permanently change nutrition and physical exercise of the obese children and adolescents. However, long-term results of treatment programmes in European countries are scarce and the reported results, even of multidisciplinary regimens, are not impressive. Conclusion In most European countries there is an urgent need not only for a growing awareness of the problem of obesity in children and adolescents but also for development of new comprehensive approaches in treating this group.