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。     

2132例矮小症患儿病因及骨龄分析

目的探讨矮小症患儿的病因分类及其骨龄落后情况。方法回顾性分析2009年1月至2014年12月住院治疗2 132例矮小症患儿的临床资料。结果 2 132例矮小症患儿中男1 333例、女799例,平均年龄(9.03±3.04)岁,平均骨龄(6.81±3.05岁);完全性生长激素缺乏症324例(15.20%),部分性生长激素缺乏症780例(36.58%),多垂体激素缺乏症27例(1.27%),甲状腺功能减低症13例(0.61%),特发性矮小893例(41.89%),低出生体质量儿19例(0.89%);骨骼发育障碍8例(0.38%),颅内肿瘤13例(0.61%),慢性系统性疾病15例(0.70%),染色体疾病40例(1.88%)。ANOVA分析显示,不同病因组骨龄落后情况不同,多垂体激素缺乏症、颅内肿瘤导致的矮小症骨龄落后较其余各病因组明显。生长激素峰值与骨龄落后值之间存在负相关关系。结论生长激素缺乏症是矮小症最常见病因。矮小症患儿普遍存在骨龄落后,骨龄落后值与生长激素峰值之间存在负相关关系,联合激素缺乏对骨龄的影响更为显著。     

不同病因矮身材儿童TW2-R、C、T骨龄评分特征研究

目的　探讨不同病因矮身材儿童TW2-R、C、T骨龄评分特征, 为矮身材的病因诊断提供参考。方法　以363例未经治疗的矮身材儿童为研究对象, 根据病因分为4组：生长激素缺乏症(GHD, 27例)、特发性矮小(ISS, 280例)、小于胎龄儿(SGA, 41例)、Turner综合征(TS, 15例)。拍摄左手腕骨骨龄片, 应用TW-2骨龄评分法对各组患儿R骨龄、C骨龄及T骨龄进行评分, 将各序列骨龄与年龄对比分析。结果　GHD组男、女儿童表现为R骨龄、C骨龄及T骨龄均较年龄落后2岁以上。ISS组男童R骨龄、C骨龄及T骨龄较年龄落后约1岁; ISS组女童各序列骨龄与年龄比较无显著差异。SGA组男女儿童各序列骨龄与年龄比较无显著差异。TS组R骨龄及T骨龄较年龄显著落后, C骨龄与年龄比较无显著差异。结论 不同病因所致的矮身材儿童具有不同的TW-2 R、C、T各序列骨龄特点。TW-2 R、C、T各序列骨龄的评估对于矮身材儿童病因的诊断具有辅助作用。     

矮小症睡眠各时相生长激素水平观察：附17例报告

本文通过对17名矮小症患儿和7名对照组小儿在脑电图监测下,测定夜睡眠中各睡眠时相生长激素(GH)分泌水平,并和药物激发试验结果比较,以简述夜睡眠中GH水平对矮小症病因诊断的临床意义。 对象和方法 一、对象 矮小症(患者组)17名中男11名,女8名;平均年龄11.4±3.6岁;体态匀称无畸形,智能正常,身高低于同年龄、性别健康儿童均数两个标准差,且身高增长每年<5cm,骨龄延迟≥2岁,临床     

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。     

儿童身材矮小的病因分析及遗传学诊断

目的 探讨身材矮小患儿的病因分布及遗传学诊断。方法 回顾性分析86例身材矮小患儿的病因分布及临床特征。结果 86例身材矮小患儿中,病因有6种,以特发性矮小症（ISS,41%）和生长激素缺乏症（GHD,29%）最常见,遗传性疾病（14%）次之。将遗传性疾病组与ISS组、GHD组比较显示,各组患儿就诊年龄、身高、出生身长、出生体重、父母身高及胰岛素样生长因子1（IGF-1）水平差异均无统计学意义（P > 0.05）,但遗传性疾病组身高距同年龄同性别个体身高第3百分位数的差值（ΔP3）和身高标准差评分（HtSDS）显著低于ISS组（P < 0.05）,但与GHD组相比差异无统计学意义（P > 0.05）。对遗传性疾病组患儿的临床表现进行分析,显示不同遗传性疾病表型谱存在异质性及表型重叠性。结论 ISS、GHD和遗传性疾病是儿童身材矮小的主要病因。对存在严重身材矮小的患儿,在除外GHD外,有必要进一步行遗传学检查明确诊断。     

骨龄和遗传身高对重组人生长激素治疗生长激素缺乏症患儿疗效的影响

目的 观察重组人生长激素(rhGH)治疗原发性生长激素缺乏症(GHD)患儿的疗效,分析开始治疗时骨龄和遗传身高(FPH)对GHD治疗效果的影响.方法 对GHD患者应用国产rhGH治疗,选取其中36例完全性GHD男性青春期前患者,按骨龄不同将36例患者分成骨龄<9岁组(19例)和骨龄≥9岁组(17例);按FPH不同将36例患者分成FPH<170.79 cm组(13例),170.79 cm≤FPH<174.69 cm组(14例)和FPH≥174.69组(9例),分别进行治疗后0.5 a平均生长速率(GV)监测.结果 治疗时骨龄<9岁组GV值为(12.9±1.8)cm/a,明显大于骨龄≥9岁组[(9.2±2.1)cm/a](t=2.31 P<0.05);FPH≥174.69组GV值为(12.4±2.1)cm/a,明显大于FPH<170.79组[(10.1±2.0)cm/a](t=2.26 P<0.05).结论 开始治疗时骨龄和遗传身高对GHD患儿的促生长疗效存在显著影响.     

身材矮小儿童523例病因分析

目的探讨身材矮小儿童的病因。方法矮小儿童共523例,其中男365例(69.79%),女158例(30.21%);平均年龄10.91岁。对其进行全面的病史采集和体格检查及相关实验室检查。结果生长激素缺乏症115例占21.99%;体质性青春发育延迟100例占19.12%;家族性矮小97例占18.55%;特发性矮小79例占15.11%,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。结论矮小儿童中,内分泌疾病所致矮小占大多数,其中以生长激素缺乏症最为多见。对部分临床表现不典型的甲状腺功能减低症需通过实验室检查才能确诊。对矮小患儿应明确病因,给予对因治疗。     

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。     

体质量指数对精氨酸与可乐定联合激发试验中生长激素峰值的影响

目的 探讨体质量指数(BMI)对矮身材儿童精氨酸与可乐定联合激发试验中生长激素(GH)分泌峰值的影响.方法 回顾性分析81例矮小儿童身高、体质量测量数据,计算BMI；并应用单因素和多元逐步回归分析患儿精氨酸与可乐定联合激发试验中GH峰值的影响因素.结果 81例矮小儿童中男45例,女36例；年龄(7.3±2.5)岁；其中GH缺乏症(GHD) 47例,特发性矮小34例；BMI为(15.9±1.7) kg·m-2,BMI标准差积分(SDS)为-0.02±0.93.单因素分析显示GH峰值与BMI及BMI SDS呈负相关；多元逐步回归分析结果显示BMI SDS与GH峰值呈负相关、胰岛素样生长因子-1与GH峰值呈正相关；GHD发生率随BMI SDS增加而升高.结论 BMI SDS是影响激发试验中GH峰值的独立因素；在解释激发试验结果时候需考虑BMI的影响.     

�ط��԰�С������СͬԴ�л����쳣����������Ĺ�ϵ�о�

目的研究特发性矮小(ISS)中矮小同源盒基因(SHOX基因)缺失和突变及该基因增强调控序列(CNE)9的缺失与表型特征的关系。方法采用微卫星分析、外显子及增强调控序列CNE9测序对2008年7月至2010年07月从重庆医科大学附属儿童医院门诊收集的患者354例ISS患者进行SHOX基因分析,对SHOX基因异常患者的表型指标进行相关统计学分析。结果 354例ISS患者中发现SHOX基因异常37例(10.5%),其中外显子突变3例(8.1%),缺失32例(86.5%),另CNE9缺失2例(5.4%)。SHOX基因异常患者表型改变有体质指数(BMI)、坐高/身高、前臂长/上臂长增加;前臂长/身高、四肢躯干比减小、四肢躯干比小于校正身高等。结论 SHOX基因异常与表型特征指标有某些相关关系。     

Helicobacter pylori infection in patients with idiopathic short stature

BACKGROUND: Some investigators have recently described an association between Helicobacter pylori infection and children with short stature. In the present study, we aimed to evaluate children with short stature with different etiologies. METHODS: This study evaluated short patients aged from 1 to 16 years. These patients were divided into a growth hormone deficient short stature group (n = 27) and an idiopathic short stature group (n = 14). A control group included children with normal growth and no abdominal pain (n = 47). Anti-H. pylori antibodies were measured in each group (total of 88). RESULTS: The antibody positivity rates for each group were as follows: growth hormone deficient short stature group, 7.4%; idiopathic short stature group, 28.6%; and control group, 6.4%. The H. pylori antibody positivity rate in the idiopathic short stature group was significantly higher than in the control group. CONCLUSION: Our findings suggest an association between H. pylori infection and idiopathic short stature.     

Managing expectations in the child of short stature with no underlying cause

Idiopathic short stature is a common reason for referral to the general paediatric or endocrine clinic. It can negatively impact the quality of life for the child and young person, extending into adulthood for some. However, these children are healthy individuals and treatment is not usually indicated. Whilst those with constitutional delay in growth and puberty can be given hormonal supplementation to induce puberty, there is no treatment available in the UK for the remaining children and young people as growth hormone is not approved for idiopathic short stature. It is important to emphasise to the child, young person and family that they are following a normal pattern of growth to reduce the perception that there is a problem. Growth charts plotted with bone age and a target range for family size are useful for predicting adult height and managing patient and parental expectations.     

Quality of referral of short children to the paediatric endocrinologist and impact of a fax communication system

BACKGROUND/OBJECTIVES:

In 2001, a chart review of children referred to the authors’ endocrine clinic because of short stature revealed that many were referred with insufficient baseline data, had normal height velocity and were within genetic target height. Therefore, a two-way fax communication system was implemented between referring physicians and the authors’ service before the first visit. Aspects that were assessed included whether this system increased the information accompanying the patient at referral, resulted in children with nonpathological shortness not being seen in the clinic, and was used differently by paediatricians and general practitioners.

STUDY DESIGN:

Between January and December 2006, 138 referrals for short stature, diagnosed with familial short stature, constitutional delay or idiopathic short stature, were audited (69 with and 69 without previous fax communication). Data collected included source of referral, clinical information provided, available growth measurements, and results from laboratory and imaging studies.

RESULTS:

Fax communication resulted in growth curves being provided more often (95.6% of cases versus 40.5% of cases without fax communication [P<0.001]) and more investigations being performed by the referring physician (median [range]: six [zero to 13] investigations versus one [zero to 11]; P<0.001), as well as a diagnosis of nonpathological short stature being given to 31 children based on the growth curve, laboratory and imaging results, without the children being seen in the endocrine clinic. Fax communication was also used more frequently by paediatricians (84%) than by general practitioners (15%).

CONCLUSION:

The fax communication system resulted in a more complete evaluation of referred patients by their physicians and reduced the number of unnecessary visits to the authors’ specialty clinic while promoting medical education.     

Growth failure starts from early infancy in children with short stature at age 6

We compared the growth of 183 children with short stature (≤ 2SD) and 73 children of normal height at age six who were visiting the Tanaka Growth Clinic. We classified these short children as suffering from either idiopathic short stature (ISS, n = 119), GH deficiency (GHD, n = 33) or small-for-gestational-age short stature (SGASS, n = 31) on the basis of subsequent test results and other factors. We also conducted a retrospective study of changes in their height, wt and nutritional intake over time. The mean changes in height SD score from birth to 6 yr were –0.24 SD in normal height children with a normal birth length and +2.27 SD in normal height children with a low birth length. In short children, these changes were –1.93 SD for children with ISS, –2.41 SD for those with GHD and +0.58 for those with SGASS. The mean changes from birth to 6 mo were –0.84 SD, −1.03 SD and +0.38 SD in children with ISS, GHD and SGASS, respectively. The mean change in height SD score from birth to age 1 yr was –1.07 SD, –1.44 SD and +0.35 SD, respectively. The decrease in height SD score from birth to 6 mo accounted for 43.5% of the decrease in height SD score from birth to 6 yr in children with ISS and it accounted for 42.6% of the decrease in children with GHD. Only 19% of short children bottle-fed well, and 53% fed poorly, as opposed to 56% and 16% of normal height children who fed well and poorly, respectively. Post weaning, only 22% of short children ate well, and 56% fed poorly, as opposed to 53% and 17% of normal height children who fed well and poorly, respectively. These findings demonstrated that growth failure started from early infancy in ISS and GHD children. It was suggested that poor nutritional intake in infancy and early childhood was a partial cause of short stature at age 6.     

Growth hormone therapy in children with short stature: Is bigger better or achievable?

The introduction of recombinant DNA-synthesized human growth hormone in the mid-1980s, and its attendant unlimited supply, have led to wider application of growth hormone therapy in children. Over the past decade, the efficacy of growth hormone treatment in patients with Turner syndrome and chronic renal insufficiency, two conditions in which growth hormone secretion is normal, in improving growth velocity and final height, has also led to the consideration of growth hormone therapy in children with idiopathic short stature. Although thousands of patients with idiopathic short stature are currently being treated with growth hormone, the limited overall results available at this time do not show a significant improvement in final adult height despite an improvement in short-term growth velocity. Potential reasons for this outcome include 1) skeletal age advancing more rapidly than height age, 2) heterogeneity of the patient population comprising idiopathic short stature, 3) inherent inaccuracies of methodological tools, such as measurement of predicted adult height, and 4) a subset of children with idiopathic short stature who may, in fact, have partial growth hormone insensitivity. From a psychological perspective, the consensus of investigations in non-clinic-referred populations of psychosocial function in children with short stature do not indicate a disadvantage compared with children of normal height when socio-economic status is taken into consideration. These results, in conjunction with the minimal gains reported in behavioural measurements in idiopathic short children treated with growth hormone, question the traditional rationale that augmentation of growth velocity results in improvement in psychosocial well-being.     

Final height in psychosocial short stature: is there complete catch‐up?

AIM: To determine whether children with psychosocial short stature attain their genetic height potential. METHODS: We report on 18 children (10 girls, 8 boys) diagnosed by a multidisciplinary team as having psychosocial short stature. All the children had had some kind of change in their environment (9 were separated from their families), and increased their mean height velocity standard deviation score (SDS) from -0.7 (1.3) to +3.6 (4.8) (p < 0.005) as well as their height SDS from -3.0 (0.3) to -2.6 (0.9) in the first year after the change. All the patients were postpubertal and had reached their near final height (mean age, 20.0 y; range, 16.0-23.3). RESULTS: Only 3 out of 18 had a greater final height than the mid-parental target height, 14 out of 18 had a near final height within the mid-parental target range (95% tolerance limits of the mid-parental height (+/- 2 SD = +/- 10 cm). Nevertheless, mean final height expressed in height SDS for the whole group was significantly shorter with -2.4 SDS compared with the mean of the mid-parental target height of -1.5 SDS (p < 0.001). Surprisingly, initial catch-up growth did not correlate with final height attainment. CONCLUSION: The majority of patients will attain a stature within the range of mid-parental target height, although towards the lower limit of this range.     

Growth hormone treatment of idiopathic short stature: analysis of the database from KIGS, the Kabi Pharmacia International Growth Study

Within the Kabi Pharmacia International Growth Study (KIGS) database, there is information on 1017 (700 male/317 female) patients with idiopathic short stature (ISS). These patients were started on recombinant human growth hormone (GH) at a median age of 10.8 years, a bone age of -1.8 SDS, a height of -2.6 SDS and a predicted adult height (PAH) (Bailey–Pinneau method) of -2.5 SDS. The median dose of GH was 0.6 IU/kg body weight/week and the frequency of injections was six/week. According to the relationship with target height the patients were classified into'familial short stature (FSS)'(height SDS > target height SDS - 1.28) and into'non-FSS'(height SDS < target height SDS - 1.28). During the first year of GH treatment there was an overall increment in the median height velocity from 4.4 to 7.4 cm/year. Over 3 years of GH treatment, cross-sectional analysis demonstrated an overall increment in median PAH of 1.2 SDS. There was a positive correlation between gain in PAH and the GH dose (n = 202, r = 0.18, p < 0.01) during the first year. Longitudinal analysis in 84 patients showed an overall increment of PAH of 0.7 SDS over 2 years of treatment. When applying the KIGS first-year prediction model for patients with idiopathic GH deficiency on cohorts of prepubertal children with FSS and non-FSS, a lower responsiveness to GH in the non-FSS group was observed. It is concluded that higher than substitutive doses of GH are required for the long-term improvement of growth in ISS.     

Effects of 3 Years of Growth Hormone Therapy in Short Normal Children

ABSTRACT. The effect of 3 years of growth hormone (GH) treatment on growth rate, predicted height, carbohydrate and metabolic status, and thyroid function was studied in 16 short prepubertal children growing with a normal pretreatment growth rate. The height velocity SDS increased from a pretreatment value of -0.44 ± 0.33 (mean ± SD) to a value of +2.20 ± 1.03 during the first year of treatment. It was maintained at a value above zero over the subsequent 2 years. By the end of the third year of treatment, the predicted final height had increased by 6.8 cm in the boys and by 4.2 cm in the girls ( p < 0.001 and p < 0.01, respectively). Increasing the dose of GH on a body surface area basis reduced the deceleration of growth observed during the second year of treatment, leading to an improvement in height prognosis over that year. Glucose homoeostasis was achieved initially at the expense of an elevation in fasting serum insulin concentration, but this had returned to pretreatment values by the end of the second year of therapy. No effects on thyroid function were observed.