国产重组人生长激素治疗生长激素缺乏症的临床疗效

目的为评价国产重组人生长激素(r-hGH)治疗生长激素缺乏症(GHD)的有效性和安全性.方法用国产r-hGH对62例GHD患者进行了为期6个月的临床治疗.结果患儿平均身高从治疗前116.23±15.54 cm增加至122.53±15.30 crn,平均6个月净增高数为6.3±1.79 C1m,有显著性差异(P<0.01),生长速率从2.46±0.87 cm/a提高至12.61±3.58 cm/a,净生长速率为10.15±3.31 cm/a,较治疗前明显增高(P<0.01),提示r-hGH治疗GHD的促身高增长效果显著.完全性GH缺乏者治疗6个月身高净增高了6.58±1.68 cm,较部分性GH缺乏者治疗6个月身高净增高了5.28±1.91 Cm,有显著性差异,说明r-hGH治疗完全性GH缺乏者较部分性GH缺乏者更为有效.结论 r-hGH治疗GHD的疗效确切,有明显的促身高增长的作用,而对骨龄成熟无明显加速影响,该药使用安全,无明显副作用.     

生长激素受体基因多态性与生长激素促生长疗效的相关性

近年来,重组人生长激素已广泛应用于儿科临床,如生长激素缺乏症、非生长激素缺乏所致的身材矮小(如小于胎龄儿)、特发性身材矮小及Turner综合征等。生长激素的促生长作用尤为令人关注,但被治疗者个体间存在一定的药物疗效差异。已知人生长激素受体基因具有两种基因型,即第三外显子缺失型及全长基因型,并出现两种生长激素受体异构体。第三外显子缺失型的部分缺失可引起膜外区精细的构象变化,使生长激素更易触发受体活化,从而使个体对重组人生长激素的治疗较全长基因型更为敏感。该文就生长激素受体基因及其编码蛋白、生长激素受体基因多态性与蛋白异构体方面的研究予以综述,同时阐述生长激素受体基因研究对明确人体生长的生理病理过程的重要意义。     

内分泌系统疾病

981420家族性垂体性侏儒伴低血糖1例/梁黎//实用儿科临床杂志一1997,12(2).一139一140 女,2岁4个月,因生长缓慢,常晨起疲乏来诊。37周分娩。出生体重6.19,身高64cm。实验室检查:高血糖刺激试验GH峰值0.3产g/L,精氨酸加促甲状腺激素释放激素、促性腺激素释放激素刺激试验GH峰值0.2昭/L,为单纯性生长激素缺乏。其祖母身高145cm,家族中有数人表现身材矮小。本例GH一N基因正常,属于家族性垂体性侏儒第2类中的单独生长激素缺乏lB型,此型为常染色体隐性遗传,hGH治疗效果良好。(关敏) 981421 Turner综合征的生长激素水平/江静…//实用儿科临…     

生长激素治疗生长激素缺乏症时心脏结构和功能变化

目的评价用人重组生长激素（r－hGH）治疗原发性生长激素缺乏症患者时心脏结构和功能变化。方法对9例确诊为原发性生长激素缺乏患者用r－hGH治疗前后及对20例年龄、性别相匹配的正常青少年通过一维和二维心超检查。结果治疗后患儿的空间隔厚度、左室后壁厚度及心肌重量指数明显上升,与正常相比,仍有一定差异,但差异比治疗前明显缩小。结论生长激素缺乏患者心脏的结构已经受累,但功能尚未有影响,经r-hGH治疗后,心肌重量指数明显上升,提示r-hGH对改善生长激素缺乏患者心脏结构有一定作用。     

GH和氧甲氢龙联合治疗青春期女孩Turner综合征

该作者报告5例Turner综合征女孩,其中4例骨龄超过11岁开始用生长激素(GH)治疗、身高增长显著。方法以亚历山大皇家儿童医院Robert Vines生长调查中心5例Turner综合征为研究对象。平均年龄13.9岁,平均骨龄12岁,2例有阴毛但均无乳房发育,     

儿童甲状腺功能减低并发垂体增生8例报告

目的：探讨甲状腺功能减低致垂体增生的内分泌激素的改变及治疗效果。方法：回顾性分析8例甲状腺功能减低致垂体增生儿童（3例男性,5例女性,年龄5～9岁）的临床资料,治疗随访1～6年。结果：8例患儿的甲状腺激素水平均降低,促甲状腺素（TSH）及血浆泌乳素（PRL）水平增高,予以甲状腺素替代治疗,用药2～6月后,血清游离三碘甲腺原氨酸(FT3)、游离四碘甲腺原氨酸(FT4)、TSH及PRL恢复正常,垂体体积恢复正常大小。其中6 例身高增长由治疗前3.1±0.5 cm/年,提高到治疗后11.6±1.7 cm/年,差异有显著性(P<0.01)。另外2例儿童甲状腺素替代治疗后身高增长不理想,予以基因重组人生长激素（rhGH）治疗后,随访身高增长为11 cm/年。8例均无垂体增生复发。结论：对于身材矮小儿童进行甲状腺功能及垂体检查十分必要,甲状腺素替代治疗是儿童甲状腺功能减低致垂体增生的有效手段。在垂体增生恢复后仍然合并生长激素缺乏的患儿予以生长素治疗可以获得满意的身高增长。［中国当代儿科杂志,2010,12（1）：17-20］     

Crouzon综合征合并生长激素缺乏症1例报告及重组人生长激素治疗随诊

目的报告1例Crouzon综合征合并生长激素缺乏症(GHD)患儿及其重组人生长激素(rhGH)治疗结果。方法回顾分析患儿以rhGH治疗2年的临床资料。结果患儿女性,5岁4月龄时身高98.2 cm(P_3),有特殊面容(舟状头、突眼、反颌畸形等)。基因检测示FGFR2基因存在c.1061CG(p.Ser354Cys)杂合变异,源自母亲,为已知的致病变异,诊断为Crouzon综合征。同时相关检查提示患儿合并GHD。给予rhGH治疗2年,身高117 cm,平均生长速率为9.4 cm/a。治疗期间,头颅磁共振监测提示侧脑室及第三脑室略扩张等表现未进展,眼科随诊示左眼视盘水肿程度较前减轻,未发现不良反应。结论矮小可能是Crouzon综合征的表型,rhGH治疗可以改善Crouzon综合征合并GHD患儿的身高,且未引起患儿颅内压增高等不良反应。     

第二代重组人生长激素治疗20例特发性生长激素缺乏症2年临床总结

本文总结应用第二代DNA重组hGH(Genotro Pin,Sweden)连续2年治疗20例青春发育前典型严重特发性生长激素缺乏症的结果。其中男15例,女5例,治疗前均经L-Dopa和Clonidine激发试验确诊为GH缺乏,治疗剂最为0.1IU/kg·日,每天1次皮下注射,每3～6个月随访1次。治疗第一年身高增加12.0±2.1cm,治疗第二年身高增加8.2±2.2cm,效果满意。还证实治疗时的年龄、骨龄与第一年和3年的增长速率呈负相关。     

儿童矮小症应用生长激素的长期安全性

生长激素(GH)于1956年首先从人垂体中分离出,其生物化学结构直到1972年才阐明.重组DNA技术和基因工程方法,实现了人生长激素(hGH)的大规模生产,使hGH普遍利用成为可能.文章综述生长激素在儿童生长激素缺乏症、慢性肾功能不全、Turner综合征、Prader-Willi综合征、小于胎龄儿持续矮小、特发性矮小、矮小同源异型盒基因(SHOX)缺陷疾病中的应用方法和安全性.提示重组hGH用于儿童的安全性令人满意,但也需注意有潜在风险的特殊群体.     

基因重组人生长激素治疗儿童生长激素缺乏症26例

目的　探讨基因重组人生长激素 (rhGH)对生长激素缺乏症 (GHD)患儿的疗效。方法　对 2 6例GHD给rhGH治疗 ,0 .1IU/ (kg·d) ,每晚皮下注射 ,疗程 0 .5年。结果　 2 6例身高平均增加 8.2± 0 .8cm/ 6个月 ,生长速率由治疗前 1.5± 0 .4cm/ 6个月增加至 6.5± 1.7cm/ 6个月 ,身高标准差由治疗前 4.5± 1.2减少至3 .2± 1.1,骨龄无明显增加 ,体重也略有增加。治疗期间第 1～ 3个月 75 %左右患儿出现甲状腺功能低下症状 ,但未影响体格线性增长。结论　rhGH是治疗GHD的一种有效、安全的促生长药物     

Effect of Recombinant Human Growth Hormone Therapy on Bone and Clinical Parameters in Girls with Turner's Syndrome

Ferrández, A., Mayayo, E., Arnal, J.M., Garcia, C., Buduel, C., Lasarte, J.J., Anton, R., hyuelo P., and The Spanish Collaborative Group (Endocrine Unit, Children's Hospital, Miguel Servet, Zaragoza, Spain). Effect of recombinant human growth hormone therapy on bone and clinical parameters in girls with Turner's syndrome. Acta Paediatr Scand [Suppl] 356: 87, 1989.
Forty-eight girls with Turner's syndrome were assigned to one of three treatments; recombinant human growth hormone (rhGH) alone, rhGH plus oxandrolone, and rhGH plus ethinyloestradiol. Treatment with rhGH alone or in combination with oxandrolone induced catch-up growth. Older girls treated with rhGH plus ethinyloestradiol showed less marked improvement. The gain in height was associated with a gain in bone diameter and cortical thickness (reflecting increased bone mass). There was a rapid loss of subcutaneous fat. These effects of growth hormone are similar to those observed in patients with growth hormone deficiency.     

Update on the Kabi International Growth Study, April 1989

International Board, Kahi International Growth Study (Kahi, Stockholm, Sweden). Update on the Kahi International Growth Study, April 1989. Acta Paediatr Scand [Supp] 356: 173, 1989.
The efficacy and safety of recombinant human growth hormone (rhGH) treatment is under prospective evaluation in children with various short stature conditions. Of the 987 children enrolled up to April 1989, 836 (84.7%) had classic growth hormone deficiency (GHD) and 151 (15.3%) non-GHD. There was a predominance of idiopathic growth hormone deficiency (IGHD), with a ratio of IGHD to secondary or organic GHD (OGHD) of 2.2:l. There were more boys than girls in both the IGHD and OGHD groups. Isolated GHD was more common than multiple pituitary hormone deficiency except in some of the groups with OGHD. About half of the OGHD patients had GHD secondary to treatment for CNS tumours. Idiopathic short stature and Turner's syndrome were the most common diagnoses in the non-GHD group. The median age at onset of treatment in IGHD was 8.2 years for boys and 8.6 years for girls. The corresponding figures for OGHD were 14.0 years and 12.2 years, respectively. The height SDS for chronological age at the start of treatment was -3.0 for IGHD and slightly less for children with OGHD. Approximately one-third of the children had already reached puberty at the start of hGH treatment.     

Spontaneous Growth in Turner's Syndrome

Growth in Turner's syndrome can be divided into four phases: intrauterine growth is slightly retarded, normal growth occurs up to a hone age of about 3 years, with a tendency to compensate for the loss in growth during intrauterine life, stunting of growth is severe during childhood, after a hone age of about 10 years — the time when puberty normally starts - the growth phase is prolonged, hut total height gain is not essentially reduced. Based on a study of 150 patients with Turner's syndrome whose spontaneous growth was observed, standards of height and height velocity (means and SDs) were calculated to allow mathematical analysis of the spontaneous growth and growth during treatment in these patients. The auxological characteristics in Turner's syndrome do not support the assumption that GH deficiency playsa primary role in the pathogenesis of the growth disorder.     

Prediction of the growth response in children with various growth disorders treated with growth hormone: analyses of data from the Kabi Pharmacia International Growth Study

Analyses to predict the growth response to recombinant human growth hormone (GH) in prepubertal children during the first year of treatment were performed on data from 472 patients with idiopathic GH deficiency (IGHD), 202 children with Turner's syndrome, 327 children with idiopathic short stature (ISS) and 135 children with intrauterine growth retardation (IUGR). In IGHD, 56% of the variability of the response could be predicted from a model based on six variables. These variables could be ranked in order of importance as follows: target height SDS minus height SDS, chronological age, frequency of GH injections, dose of GH, weight-for-height index, and birth weight SDS. When the model for IGHD was applied to Turner's syndrome, ISS and IUGR, there was a high degree of similarity between the predicted and achieved growth response in ISS and IUGR. However, an uneven distribution within the plot of Studentized residuals in ISS and IUGR suggested heterogeneity within these populations. Prediction of growth in Turner's syndrome was greatly exaggerated by the model for IGHD, suggesting a different pathogenesis as the basis of the growth disorder. Specific prediction models were therefore developed for Turner's syndrome, ISS and IUGR. In all three disorders, the dose of GH was found to be the most important predictor, suggesting that, in contrast to IGHD, first-year growth is governed less by the difference between height and the presumed genetically determined target height. Again, in contrast to IGHD, this suggests that catch-up phenomena are not involved. As the predictability of the variation in growth response in Turner's syndrome, ISS and IUGR did not exceed 32% (for ISS), the search for new predictors should continue in these disorders.     

Concurrent occurrence of chronic lymphocytic thyroiditis with hypothyroidism and growth hormone deficiency in a Turner's syndrome patient

BACKGROUND: Concurrent deficiencies of three hormones in patients with Turner's syndrome (TS) have rarely been reported. Here, we describe a case of a young girl who had Turner's syndrome with concomitant chronic lymphocytic thyroiditis, growth hormone deficiency, and hypothyroidism with cardiopericarditis. CASE: An 11-year-old girl was referred to the outpatient clinic because of short stature, ochriasis, and cardiopalmus. Her ultrasound revealed absence of ovarian tissue. Karyotype examination suggested Turner's syndrome with sex hormone deficiency. She was found to have an abnormal thyroid gland and elevated thyroid stimulating hormone (TSH). A positive thyroid autoantibody titer confirmed the diagnosis of chronic lymphocytic thyroiditis with hypothyroidism. Furthermore, her growth hormone levels were well below normal. DIAGNOSIS: A multi-endocrine disorder, i.e., Turner's syndrome with chronic lymphocytic thyroiditis, growth hormone deficiency, and hypothyroidism with cardiopericarditis was diagnosed. Growth hormone and thyroxin substitution therapy was suggested.     

Acute metabolic effects of human growth hormone on 15N-nitrogen balance in patients with thalassaemia as compared to patients with other types of short stature

The acute response to various doses of human growth hormone (hGH) was determined in short patients with thalassaemia and compared to that in patients with classic growth hormone deficiency and Turner's syndrome. Nitrogen balance was analyzed using the stable isotope 15N. While patients with growth hormone deficiency responded with a marked nitrogen retention (+2.9 +/- 0.4 to +6.1 +/- 0.6 mg 15N/kg) to small doses of hGH (2 x 3 IU/m2), those with Turner's syndrome had a higher basal balance, but responded much less (+3.1 +/- 0.7 to +3.7 +/- 1.8 mg 15N/kg). They required a double dose of hGH (2 x 6 IU/m2) to achieve a significant retention (+4.1 +/- 1.0 to +7.1 +/- 0.4 mg 15N/kg). The thalassaemic patients responded still less than the patients with Turner's syndrome to 2 x 6 IU/m2 (+7.7 +/- 0.3 to +8.0 +/- 0.4 mg 15N/kg), and even hGH doses up to 2 x 12 IU/m2 had little effect, indicating a relative resistance to hGH. In conclusion, no or little effect is to be expected from long-term hGH treatment at low doses in thalassaemic patients. When it is decided to treat these patients, the dose should be about 4 times higher than a regular replacement dose in growth hormone deficiency.     

Change in speaking fundamental frequency in hormone-treated patients with Turner's syndrome-a longitudinal study of four cases

Change in speaking fundamental frequency for four hormone-treated girls with Turner's syndrome was registered using two computerized analysis methods for a period of four years. The girls were treated with human growth hormone, oxandrolone and ethinyl estradiol. The overall pattern for three of the girls was a distinct decline in speaking fundamental frequency during the first year, while for the fourth patient the pattern of change was more complicated. For all four girls, the final pitch level was within the normal range for adult women. It is important that voice effects are taken into account in the hormonal treatment of Turner's syndrome and that patients are informed of the changes to be expected.     

重组人生长激素的临床应用和研究进展

生长激素是由脑垂体前叶嗜酸性细胞分泌的一种蛋白质,直接或间接通过胰岛素样生长因子对生长和代谢发挥作用.生长激素可作用于人体多种组织的靶细胞,具有广泛的生理作用.随着临床研究不断深入,重组人生长激素的应用范围不再局限于治疗儿童矮小症,其在成人生长激素缺乏症、神经系统疾病如缺血缺氧性脑病、脑外伤、脑性瘫痪、阿尔茨海默病等疾病以及烧伤领域、辅助生殖等方面均有一定的临床意义.该文就国内外重组人生长激素临床应用和研究最新进展作一综述.     

Effect of growth hormone treatment on craniofacial growth in Turner's syndrome

A cephalometric study was performed in 19 patients with Turner's syndrome, aged 8.7–16.5 years. A lateral roentgencephalogram was taken before and after two years of treatment with biosynthetic growth hormone in a dose of 24 IU/m²/week. During two years of growth hormone treatment, the mandibular length increased mainly due to vertical growth. The initially posteriorly rotated mandible showed an anterior rotation, although the normal position was not reached. The other linear measurements and angles did not change during treatment. No indications were found for an increase in the disproportionate growth or for excessive chin growth as a sign of acromegaly during growth hormone treatment. In conclusion, growth hormone treatment in patients with Turner's syndrome resulted in an increase in mandibular length, mainly due to vertical growth of the ramus and in the anterior rotation of the mandible.     

An Overview of the Diagnoses in the Kabi Pharmacia International Growth Study

This paper provides an overview of the diagnoses of patients entered in the Kabi Pharmacia International Growth Study (KIGS). By May 1991, data from a total of 5377 children treated with growth hormone (GH) were included in the main database. Of these children, 2691 were classified as having idiopathic GH deficiency (GHD), 866 as having GHD of known origin, and 1820 as having other causes of short stature. The majority of patients with idiopathic GHD have no history of perinatal trauma. In the patients with GHD of known origin, 137 were congenital cases and 729 acquired GHD. The largest number of congenital cases (114) belonged to the group of central malformations (e.g. septo-optic dysplasia and empty sella syndrome). Of the cases with acquired GHD, 73% were associated with tumours or leukaemia. Other causes of short stature include 12 groups of diagnoses, with more than 150 cases in four of them (idiopathic short stature, 635; defined syndromes with chromosomal aberrations, 337, of which 304 were Turner's syndrome; defined syndromes without chromosomal aberrations, 157; intrauterine growth retardation without stigmata, 366). Analysis of the KIGS data allows modern GH therapy for GHD to be compared with older treatment modalities. The study offers the advantage of larger numbers of cases than can be achieved in individual trials and allows assessment of the use of GH therapy for GHD of comparatively uncommon causes.