Growing up with idiopathic short stature: psychosocial development and hormone treatment; a critical review

To facilitate decisions on interventions in medically referred children with idiopathic short stature, the research on psychosocial functioning of these children, possible risk and protective factors influencing adaptation, and effects of hormone treatment were reviewed. Parents ranked the behaviour of their children on average between normal and below normal. The magnitude of these deviations varied from small to large. Little is known about the children's self-perceived psychosocial functioning. Some risk factors were found: being teased, being juvenilised, being a boy, having a younger but taller sibling, low intelligence, and low socioeconomic status. There have been few studies on the impact of protective factors including temperament, coping strategies, and social support. On average, hormone treatment did not improve psychosocial functioning. The research shows the advantages and disadvantages of hormone treatment that must be considered when choosing a suitable intervention. It is suggested that psychosocial adjustment can be improved by focusing on factors other than height alone.     

Three-year data from a comparative study with recombinant human growth hormone in the treatment of short stature in young children with intrauterine growth retardation

Growth acceleration and bone maturation were studied for 3 y in 69 children with severe short stature and a history of intrauterine growth retardation (IUGR), to determine the effect of treatment with recombinant human growth hormone (r-hGH). The patients were enrolled in an open, multicentre trial and were randomly allocated to either the treated group (Group 1) or the control group (Group 2). The children in Group 1 were treated daily with 0.2 IU/kg/body weight (0.067 mg/kg) s.c, during 3 y and the children in Group 2 started the study with a 1-y observation period followed by a 3-y treatment period. At birth, their mean weight standard deviation score (SDS) was -2.5 and their mean length SDS -3.5. At baseline, the patients were prepubertal, non-GHdeficient, with no known dysmorphic features. Mean age was 4.5 y, bone age was 3.3 y, height SDS was -3.4, height velocity (HV) SDS was -1.6, and body mass index SDS was -1.4. After 1 y of treatment, linear HV in Group 1 increased in comparison with the pre-treatment period (from 5.7 ± 2.0 to 10.1 ± 1.7cm/y; p < 0:001)and with the firstyear of observation in Group2( p < 0:001). Increased HV was sustained during the second and third year of treatment and was significantly higher than at baseline. A similar growth pattern was seen during the 3y of GH treatment in Group 2. Mean height SDS for chronological age increased by 2.0 ± 0.7 in the two groups after 3 y of treatment. HV after 1 y of treatment was negatively correlated with growth velocity at baseline. Bone age remained retarded but increased with a mean of almost 4 y after 3y of treatment in both groups. Even at a dose that is three times the replacement dose treatment with r-hGH was well tolerated. From these results, we conclude that r-hGH treatment over 3 y can induce sustained catch-up growth in young children with severe short stature and a history of IUGR. Long-term studies are needed to assess ultimate effects on final height.     

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.     

Long-term psychosocial consequences of hormone treatment for short stature

AIM: To examine psychosocial functioning of young adults with idiopathic short stature or short stature born small for gestational age after growth hormone (GH) and gonadotropin-releasing hormone agonist (GnRHa) treatment in early adolescence or no intervention. METHODS: Thirty young adults (18 treated, 12 untreated; age 17-23 years; on average 5.5 years after the end of treatment) completed questionnaires regarding perceived competence and psychological distress. They and their parents were interviewed on social circumstances, height-related psychosocial stressors and parental worries about prospects in society. RESULTS: Height gain was on average 2.3 cm more for the treated than for the untreated group. On none of the psychosocial variables differences were found between treated and untreated participants. Compared to Dutch population norms, psychological and social functioning was normal. CONCLUSION: GH/GnRHa treatment, with arrest of pubertal development and lower than expected effects on final height, is not observed to lead to long-term negative or positive effects. Both treated and untreated participants go well through the psychosocial transition period of young adulthood. This suggests that, in the long term and independent of hormone treatment, adequate psychosocial adjustment is expected in case of short stature.     

Once versus twice daily injections of growth hormone in children with idiopathic short stature

The aim of this study was to compare the growth response of 22 short pre-pubertal children without growth hormone deficiency, treated with a single daily growth hormone injection (group A), to the growth response of 27 similar children, treated with the same daily dose divided into 2 subcutaneous injections per day (group B), for 1 y, in a randomized study. GH treatment significantly promoted growth parameters, height standard deviation score and height velocity standard deviation score in both groups. Serum insulin-like growth factor I was also increased. There were no significant differences in growth response, serum IGF-I levels, or the advance in bone age between the two study groups after 1 y of GH therapy. We conclude that twice daily s.c. growth hormone injections provide no advantages over once daily injection of the same dose in promoting the linear growth of short children without growth hormone deficiency.     

Physiological Growth Hormone Secretion and Response to Growth Hormone Treatment in Children with Short Stature and Intrauterine Growth Retardation

Stanhope, R., Ackland, F., Hamill, G., Clayton, J., Jones, J. and Preece, M.A. (Department of Growth and Development, Institute of Child Health, London and Serono Laboratories, UK). Physiological growth hormone secretion and response to growth hormone treatment in children with short stature and intrauterine growth retardation. Acta Paediatr Scand [Suppl] 349: 47, 1989.
Physiological growth hormone (GH) secretion was examined in 31 children (8 girls, 23 boys) with short stature secondary to intrauterine growth retardation (IUGR). Seventeen (4 girls, 13 boys) had dysmorphic features of Russell-Silver syndrome. Four of the 31 children had GH insufficiency with peak GH levels of < 20 mU/I during the night. Nine of the patients (8 of whom had Russell-Silver syndrome) had a single nocturnal GH pulse. Twenty-three children (6 girls, 17 boys) were randomized into two groups treated with either 15 or 30 U/m²/week of GH by daily subcutaneous injections. Age, sex distribution, pretreatment height velocity SD score (SDS), and distribution of dysmorphic and non-dysmorphic children were similar in both groups. The group treated with 15 U/m2/week for a mean of 0.82 years showed an increase in mean height velocity SDS from - 0.61 to +1.09, and the group treated with 30 U/m²/week for a mean of 0.92 years showed an increase in mean height velocity SDS from -0.69 to +3.48. The results suggest that physiological GH insufficiency is probably common in children with Russell-Silver syndrome and that both dysmorphic and non-dysmorphic children with short stature secondary to IUGR will respond to GH treatment. Initial evidence suggests that the increase in short-term growth velocity does not result in an improved final height prognosis.     

基因重组生长激素治疗青春期前特发性矮小疗效观察

目的探讨基因重组人生长激素（rhGH）对青春期前特发性矮小（ISS）的疗效。方法观察27例青春期前特发性矮小患儿,平均年龄（8.9±2.0）岁,身高（118.0±10.6）cm。治疗组13例,男10例,女3例,均接受基因重组人生长激素治疗,剂量（0.12±0.01）IU/kg,睡前皮下注射,疗程6个月至1年;对照组14例,男6例,女8例。结果治疗组患儿生长速率（GV）由治疗前（4.28±0.86）cm/a提高到（9.38±1.77）cm/a,P〈0.01;年龄身高标准差积分（HtSDSCA）由-2.28±0.48增至-1.72±0.62（P〈0.01）;骨龄身高标准差积分（HtS-DSBA）由-0.24±1.02增至0.27±0.99（P〈0.05）;与对照组比较,GV、HtSDS（CA）和HtSDS（BA）差异均有统计学意义（P均〈0.05）;两组△BA/△CA比较差异无统计学意义（P均〉0.05）。结论GH治疗能改善ISS儿童的GV及HtSDS（CA）、HtSDS（BA）,而骨龄（BA）加速不明显,疗效肯定。     

Debate: Idiopathic short stature should be treated with growth hormone

In this paper we outline the case for and against the treatment of idiopathic short stature with growth hormone. Drs Ambler and Fairchild argue that many of those with ‘idiopathic’ short stature are not ‘short, normal children’ and will ultimately receive molecular diagnoses. They also argue that there is a subset of children who suffer negative psychosocial consequences of their stature for whom growth hormone therapy is effective. Growth hormone has a very good safety record and is likely to be as cost‐effective in idiopathic short‐stature as in some other conditions that are currently funded. Dr Wilkinson counters that short stature is not associated with physical or psychological illness, and that there is no evidence that growth hormone improves psychological or physical wellbeing. Moreover, growth hormone for idiopathic short stature represents a form of enhancement rather than treatment, and is not a fair use of resources. Socially mediated disadvantage should be treated by attention to prejudice and not by hormone treatment.     

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 for short stature in Diamond Blackfan anemia

BACKGROUND: We report a 13-year-old male with Diamond Blackfan anemia and short stature. He had a normal biochemical response to growth hormone (GH) stimulation, but his bone age was delayed, his insulin-like growth factor 1 (IGF-1) was low, and he had a poor growth velocity. He was started on daily GH injections. METHODS: From the patient's medical record the following data were collected: serial heights, serial weights, hemoglobin, hematocrit, bone age, IGF-1, and steroid dose. RESULTS: This patient had an increase in growth velocity up to 8.2 cm/year. CONCLUSIONS: Growth hormone therapy should be considered in children with DBA, short stature and poor growth velocity.     

重组人生长激素改善ACAN基因变异致家族性矮小的疗效观察及文献复习

目的观察重组人生长激素(rhGH)改善ACAN基因变异致家族性矮小患者身高的疗效。方法回顾分析2个ACAN基因变异致家族性矮小家系rhGH治疗的临床资料,并检索相关文献进行分析。结果先证者1,男,4岁1个月,身高90.5 cm(-3.6 SD),体质量13.5 kg,无明显骨骼畸形;骨龄示5岁6个月龄;基因检测示ACAN基因c.5026_5027del(p.Ser 1676 Ter)杂合缺失变异;予rhGH,50μg/(kg·d)治疗,第1年身高增加13 cm(103.5 cm,-1.8 SD),至第18个月身高增加17.1 cm(107.6 cm,-1.7 SD)。先证者2,男,3岁,身高82 cm(-3.9 SD),体质量12 kg,无明显骨骼畸形;骨龄示1岁6个月龄;基因检测示ACAN基因c.1504C>T(p.R 502C)杂合错义变异;予rhGH,33μg/(kg·d)治疗,第1年身高增加12 cm(94.0 cm,-2.6 SD),至第22个月身高增加17 cm(99.0 cm,-2.68 SD)。结论ACAN基因c.5026_5027 del杂合缺失变异以及c.1504C>T错义变异可引起家族性矮小;rhGH治疗短期可有效改善ACAN基因致家族性矮小患儿的身高。     

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。     

Assessment of short stature in very low birthweight children

Abstract  The aims of this study of short very low birthweight (VLBW) children at or after 8 years of age were to determine: (i) if there were any unsuspected organic causes for their growth failure; and (ii) whether any children might be suitable for treatment with synthetic growth hormone. Thirty-seven of 195(19%) VLBW children seen at 8 years had heights <10th centile, and of these only 40% (10/25) of families offered an assessment were concerned enough to have the child fully evaluated. No child had an unsuspected organic cause of short stature. The children's parents were significantly shorter than expected for Caucasians (mean parental height s.d. score =– 1.06 (s.d. 0.72), t =– 5.9, P<0.001). On average, the bone age of the short children was delayed by 14.9 months (s.d. 18.8 months) compared with chronological age ((=–3.4, P<0.01). When compared with their parents, the children's mean height s.d. score for their bone age was not significantly different (mean height s.d. score for bone age = - 0.83 (s.d. 1.3), t = 0.6, NS). Only three children qualified for treatment with synthetic growth hormone; all three had been small for gestational age at birth and had birthweights <1000 g. In conclusion, in short VLBW children, only a minority of families and children are likely to be concerned enough about short stature to be fully assessed; an unsuspected organic cause for growth failure is unlikely, and only a few will qualify for synthetic growth hormone therapy.     

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目的调查肥胖及矮小儿童自我意识水平,探讨其与正常儿童自我意识方面的差异。方法 2008年8月至2008年12月用Piers-Harris儿童自我意识量表对湖南省长沙市7所中学中86例肥胖及69例矮小儿童进行心理健康调查。结果肥胖儿童在行为、躯体外貌、合群、焦虑及自我意识总分得分均低于全国常模水平,差异有统计学意义(P<0.05或0.01);肥胖儿童在智力与学校及幸福与满足两个分量表得分与全国常模水平的差异无统计学意义(P均>0.05)。矮小儿童在行为、躯体外貌、幸福与满足、合群及自我意识总分得分均低于全国常模水平,差异有统计学意义(P<0.05或0.01);矮小儿童在智力与学校表现及焦虑两个分量表得分与全国常模水平差异无统计学意义(P均>0.05)。结论肥胖及矮小儿童自我意识水平较正常同龄儿童低,且其自我意识水平高低程度不一。青少年的自我意识水平与躯体疾病密切相关,有必要在医学治疗的基础上加入相应的心理干预措施以促进其身心健康。     

Growth hormone treatment of short children born small-for-gestational-age: the Nordic Multicentre Trial

The aims of this study were to evaluate the efficacy and safety of different doses of growth hormone (GH) treatment in prepubertal short children born small-for-gestational-age (SGA). Forty-eight children born SGA from Sweden, Finland, Denmark and Norway were randomly allocated to three groups: a control group of 12 children received no treatment for 2 y, one group was treated with GH at 0.1 IU/kg/d (n = 16), and one group was treated with GH at 0.2 IU/kg/d (n = 20). In total 42 children completed 2 y of follow-up, and 24 children from the treated groups completed 3 y of treatment. Their mean (SD) age at the start of the study was 4.69 (1.61) y and their mean (SD) height was -3.16 (0.70) standard deviation scores (SDS). The children remained prepubertal during the course of the study. No catch-up growth was observed in the untreated group, but a clear dose-dependent growth response was found in the treated children. After the third year of treatment, the group receiving the higher dose of GH, achieved their target height. The major determinants of the growth response were the dose of GH used, the age at the start of treatment (the younger the child, the better the growth response) and the family-corrected individual height deficit (the higher the deficit, the better the growth response). Concentration of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 increased during treatment. An increase in insulin levels was found without negative effects on fasting glucose levels or glycosylated haemoglobin levels. GH treatment was well tolerated. In conclusion, short prepubertal children born SGA show a dose-dependent growth response to GH therapy, and their target height SDS can be achieved within 3 y of treatment given GH at 0.2 IU/kg/d. However, the long-term benefit of different regimens of GH treatment in children born SGA remains to be established.     

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…     

Castleman disease in a child with short stature

We report a 14‐year‐old boy with Castleman disease in this article. He complained of short stature, and his body height was 133.8 cm (<3rd percentile; z score ?4.5). There was marked delay in the appearance of secondary sexual characteristics. He was found to have a remittent fever and a lower mid‐abdominal tumor. Blood test revealed microcytic hypochromic anemia, thrombocytosis, polyclonal hypergammaglobulinemia, hyperfibrinogenemia, and elevated erythrocyte sedimentation rate. The serum IL‐6 and C‐reactive protein levels were increased. The mass was found to be mixed hyaline vascular and plasma cell type of Castleman disease through a pathological examination. Lymph nodes affected by Castleman disease cause overproduction of IL‐6. It decreases IGF‐1, IGFBP‐3 and serum testosterone levels. As a result of tumorectomy, his short stature and delay in the development of secondary sexual characteristics were improved.     

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.     

儿童特发性矮小临床治疗新进展

特发性矮小是一种在儿童中较常见的身材矮小,其病因及发病机制尚不明了,迄今尚无确切的治疗方案.目前对儿童特发性矮小的临床治疗丰要集中在重组人生长激素(rhGH)、促性腺激素释放激素类似物(GnRHa)和芳香化酶抑制剂(AI).文章就其新研究新进展进行综述.