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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.     

生长发育迟缓与胰岛素样生长因子的关系

目的提高由于生长激素－胰岛素样生长因子（ＧＨ－ＩＧＦ）轴异常引起的生长发育迟缓诊断的准确性。方法分别收集门诊６８例生长发育迟缓儿童运动激发试验前后２次血清和１４例住院患儿药物激发试验１０次血标本,用免疫放射计量（ＩＲＭＡ）方法测定ＩＧＦ－１,ＩＧＦ－２和ＩＧＦＢＰ－３,放免方法（ＲＩＡ）测定ＧＨ。结果药物激发试验ＧＨ水平与ＩＧＦ－１,ＩＧＦ－２和ＩＧＦＢＰ－３测定一致。运动激发试验根据运动后ＧＨ水平及身高百分位的情况将６８例分为３组：ＧＨ＜５０μｇ／Ｌ,５０～１００μｇ／Ｌ,＞１００μｇ／Ｌ。ＧＨ＜５０μｇ／Ｌ组１４例,其中１０例身高小于第３百分位,其ＩＧＦ－１,ＩＧＦ－２和ＩＧＦＢＰ－３水平分别是（３９±２０）,（２７４±１２２）,（４２０±２１０）ｎｍｏｌ／Ｌ,低于正常值（Ｐ＜００１）,ＧＨ水平与ＩＧＦ－１,ＩＧＦ－２和ＩＧＦＢＰ－３相符。结论用运动激发试验联合测定ＧＨ、ＩＧＦ－１和ＩＧＦＢＰ－３三项指标可以提高由于ＧＨ－ＩＧＦ轴异常所引起的生长发育迟缓诊断的准确性。     

Effect of somatomedin-C/insulin-like growth factor I and growth hormone on cultured growth plate and articular chondrocytes

To determine whether growth hormone has a direct effect on skeletal tissues not mediated by somatomedins, and to better define the role of somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) in skeletal development, bovine growth plate, and rabbit articular and growth plate chondrocytes in primary culture were evaluated under a variety of experimental conditions designed to elicit growth hormone and Sm-C/IGF-I stimulation. Under none of these conditions did bovine growth plate chondrocytes respond to either homologous bovine growth hormone or heterologous hGH. Under the same conditions, these cells were highly responsive to human Sm-C/IGF-I with respect to both [3H]thymidine and [35S]sulfate incorporation, indices of mitotic and differentiated cell functions, respectively. Similarly, both rabbit articular and growth plate chondrocytes showed enhanced incorporation of [3H] thymidine and [35S]sulfate in the presence of Sm-C/IGF-I, but did not respond to either native or recombinant hGH. Cells at different stages of maturation within the bovine growth plate differed in their reaction to Sm-C/IGF-I with proliferative zone cells manifesting a greater response to the peptide than cells of the reserve zone. These results suggest that the action of Sm-C/IGF-I on growth plate and articular chondrocytes is direct and that the effect of GH on these cells is indirect. The data further suggest that within the growth plate, the transition from reserve to proliferative status is associated with an increased Sm-C/IGF-I responsiveness, a change which may contribute to the functional differences in these cells.     

Craniofacial and acral growth responses in growth hormone-deficient children treated with growth hormone

OBJECTIVES: To investigate the effects of growth hormone (GH) therapy on craniofacial growth and body proportions in growth hormone deficient children. STUDY DESIGN: By using a cross-sectional study design, we investigated GH effects on craniofacial growth with photographic facial morphometrics, head circumference, and hand and foot size in 52 children with GH deficiency (GHD) treated with GH (0.27 mg/kg/wk) for 0.19 to 15.5 years, compared with untreated children with GHD and normal first-degree relatives. To detect disproportion and to correct for stature, age and height age (HA) SD scores were analyzed. RESULTS: Untreated subjects with GHD had retarded facial height and width (P values=.001) compared with normal controls; small head circumference for age and HA (P=.001); small hands for age (P<.001) that were large for HA (P=.003); and small feet for age (P<.001) that were normal for HA. When compared with normal controls, GH-treated subjects had proportional facial heights but narrower facial widths. Head circumference, however, increased disproportionately to height (P=.001), becoming large for stature, and increasing with duration of therapy and cumulative GH dose (P<.001). Hands and feet grew proportionately to height. CONCLUSION: Growth hormone treatment with conventional doses partially corrects craniofacial deficits and does not adversely affect hand and foot growth but appears to result in excessive head circumference growth.     

The dosage dependency of growth and maturity in growth hormone deficiency treated with human growth hormone

A group of 11 pre-pubertal growth hormone deficient patients were treated with human growth hormone over a period of 4 years. In 6 of the patients the dosage was 4 IU 3 times a week and in 5, 8 IU 3 times a week. Changes in height demonstrated that the "catch up" was significantly greater and of longer duration in the second group. In spite of a more rapid increase of bone age in the second group, the prognosis of final height had improved significantly at the end of the study period. A comparative study of the plasma concentrations significantly at the end of the study period. A comparative study of the plasma concentrations of T4, TSH, gonadotrophins and steroids, to see if the greater velocity of bone maturity in the second group could be due to contamination of the preparation by other could be due to contamination of the preparation by other hypophysary hormones, did not demonstrate significant differences between the groups.