Growth Response in the First Year of Growth Hormone Treatment in Prepubertal Children with Organic Growth Hormone Deficiency: a Comparison with Idiopathic Growth Hormone Deficiency

ABSTRACT. Patients in the Kabi International Growth Study (KIGS) up to 1st January 1990 who had organic growth hormone deficiency (OGHD) were identified. They accounted for 21% of all patients with growth hormone deficiency (GHD). Diagnostic categories within the OGHD group included septo-optic dysplasia, postnatal trauma, craniopharyngioma, other cranial tumours, and following acute leukaemia. Features at presentation and during the first year of hGH treatment were compared with those of children with idiopathic growth hormone deficiency (IGHD). Ninety prepubertal children with OGHD were selected for comparison of observed first-year height velocity (HV) with predicted values based on those observed in 257 children with IGHD. Those with septo-optic dysplasia, postnatal trauma and craniopharyngioma responded as predicted, whereas those with other cranial tumours appeared to grow less well than predicted. Glucocorticoid treatment did not affect response, but previous cranial or craniospinal irradiation was found to be associated with an observed HV which was significantly less than predicted.     

Growth Response in Prepubertal Children with Idiopathic Growth Hormone Deficiency during the First Year of Treatment with Human Growth Hormone. Analysis of the Kabi International Growth Study.

ABSTRACT. In order that children with growth hormone deficiency (GHD) reach the goal of normal adult stature, treatment modalities need to be optimized. From the large database of patients enrolled in the Kabi International Growth Study (KIGS), 257 prepubertal patients with idiopathic GHD undergoing their first year of growth hormone (GH) substitution therapy were selected. A multiple regression analysis was performed to determine both auxiological factors characterizing the patients and the factors related to the chosen treatment modalities which are of significance for the observed magnitude of the growth response. Due to the structure of the data, pretreatment height velocity and bone age-derived auxiological data were not considered. It was observed that the magnitude of the growth response was inversely correlated with chronological age and relative height (HT SDS) at the start of GH treatment but was positively correlated with mid-parental height. The growth response was also positively correlated with the GH dose (IU/kg/week) and the frequency of GH injections per week. A regression equation using these five parameters was derived, allowing the growth response of these patients to be predicted. The extension of this analytical approach in the future will allow the treatment of patients with GHD to be tailored to individual requirements.     

Growth Response in Prepubertal Children with Idiopathic Growth Hormone Deficiency During the First Two Years of Treatment with Human Growth Hormone. Analysis of the Kabi Pharmacia International Growth Study

From the large database of patients enrolled in the Kabi Pharmacia International Growth Study (KIGS), 289 prepubertal patients with idiopathic growth hormone deficiency (GHD), treated for 2 years with growth hormone (GH) substitution therapy, were selected. A multiple regression analysis was performed to determine both the auxological factors characterizing the patients at the beginning of the first and second years on GH therapy and the respective treatment modalities relevant to the magnitude of the growth response. It was observed that during the first year on GH therapy the magnitude of the growth response was negatively correlated with chronological age and height SDS, and positively correlated with target height SDS, GH dose (IU/kg/week) and frequency of GH injections. During the second year the growth response was negatively correlated with chronological age and the first-year GH dose (IU/kg/week), and positively correlated with height velocity during the first year, GH dose (second year), and injection frequency (second year). The data suggest that the forces of'catch-up'- auxologically entrenched within the distance between target height SDS and height SDS - no longer prevail during the second year of GH therapy. The inverse influence of the first-year GH dose in the two yearly phases of growth suggests that optimizing GH treatment must be attempted by analysing growth in response to GH over longer periods of time and considering that the growth process is influenced by interactive factors.     

重组人生长激素替代治疗对生长激素缺乏症患儿糖代谢的影响

目的观察国产重组人生长激素(r-hGH)替代治疗对生长激素缺乏症(GHD)患儿糖代谢的影响。方法用国产r-hGH对GHD 15例患儿治疗3个月。治疗前后行口服葡萄糖耐量试验(OGTT)及胰岛素(INS)释放试验(IRT)。分别于0、30 mun,1、2 h采静脉血行血浆葡萄糖(PG)及胰岛素(INS)测定。结果治疗前患儿糖耐量均正常,治疗3个月后OGTT空腹PG 无明显增加,但PG 30min(P<0.01)、1 h(P<0.05)、2 h(P<0.05)、血糖曲线下面积(AUCglu)(P<0.01)均明显增加;虽葡萄糖耐量曲线上移,但均未出现糖耐量损伤(IGT)或糖尿病(DM)。IRT空腹INS(P<0.05)、30 min(P<0.05)、1 h(P<0.01)、2 h(P<0.01)、INS曲线下面积(AUCins)(P<0.01)均显著增加,稳态模型胰岛素抵抗指数(Homa IR)明显上升(P<0.05)。结论GHD患儿r-hGH替代治疗3个月后INS敏感性下降,糖耐量降低,提示应用r-hGH替代治疗患儿应监测PG、INS水平     

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.     

重组人生长激素对生长激素缺乏儿童脂代谢和脂联素水平的影响

目的研究重组人生长激素(rhGH)对生长激素缺乏症(GHD)患儿脂代谢和脂联素水平的影响。方法对53例GHD患儿及33例年龄、性别相匹配的正常对照儿童,及接受rhGH治疗时间达1年以上的23例GHD患儿检测血三酰甘油(TG)、总胆固醇(TC)、胰岛素样生长因子-1(IGF-1)和脂联素水平,比较GHD组与正常对照组及rhGH治疗前后血脂和脂联素水平变化。结果GHD患儿53例中高脂血症22例(41.5%),GHD与对照组血TG、TC分别为(1.6±1.6)vs(1.1±0.4)mmol/L、(4.5±0.8)vs(4.1±0.6)mmol/L,两组比较有显著差异(P均<0.05);经rhGH治疗后,GHD患儿TG、TC均明显下降,而IGF-1明显升高,治疗前后比较均有显著差异(P<0.01,0.05);治疗后脂联素水平略上升,但治疗前后比较无显著差异。多元回归分析显示,IGF-1与年龄呈正相关,与其他因素无关;脂联素与TG呈负相关。结论GH可能直接参与GHD患儿血脂的调节,脂联素可能部分参与TG的代谢。     

The Dosage Dependency of Growth and Maturity in Growth Hormone Deficiency Treated with Human Growth Hormone

ABSTRACT. 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 of T4, T SH, 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.     

重组人生长激素治疗颅咽管瘤术后生长激素缺乏症

目的探讨低剂量基因重组人生长激素(rhGH)治疗颅咽管瘤术后生长激素缺乏症(GHD)患儿的疗效和安全性。方法回顾性分析2008年4月-2011年4月在北京三博脑科医院内分泌门诊治疗的12例7～15岁术后病理确诊为颅咽管瘤且继发生长迟滞患儿的病例资料及随访资料。患儿均给予rhGH治疗(每晚睡前皮下注射0.1 IU.kg-1,每周5次注射),疗程3～36个月。定期检测肝功能、肾功能、激素水平等指标,并比较患儿治疗前后身高、体质量、生长速度、身高标准差计数、胰岛素样生长因子1(IGF-1)、骨龄等生长指标的改变。结果在rhGH治疗期间,12例患儿在治疗第1年生长速率增加显著,由(2.2±1.3)cm.a-1增加到(6.63±4.97)cm.a-1(P<0.01),身高标准差计数由治疗前-3.3±2.3增加到-3.2±2.8,血IGF-1治疗前为(38±64)μg.L-1,治疗后为(173±167)μg.L-1(患儿治疗后血清IGF-1水平达到正常范围),差异均有统计学意义(Pa<0.01)。治疗期间,患儿肝肾功能等均保持在正常值范围,骨龄无明显变化,随访时尚无患儿肿瘤复发。结论低剂量rhGH治疗儿童颅咽管瘤术后继发GHD是经济、有效的,在充分评估及严密监控下开展GH替代治疗是安全的。     

Immune Function in Growth Hormone-Deficient Children Treated with Biosynthetic Growth Hormone

ABSTRACT. Conflicting data regarding the immune function in growth hormone (GH) -deficient children or changes in immune parameters during substitutive GH therapy have been reported. We have studied the immune function in 13 patients with GH deficiency before and during treatment with biosynthetic GH (12 IU/m² body surface/week) after 6 and 12 months of therapy. We found that the absolute number of total T lymphocytes and T-cell subsets (using monoclonal Ab as markers), Natural Killer cell activity (target K562) and response of lymphocytes to polyclonal mitogens (PHA, ConA, PWM) were all in the normal range and remained so after 6 and 12 months of therapy. The absolute number of B lymphocytes was in the normal range before treatment and after 6 months of therapy but dropped significantly after 12 months of treatment. Serum immunoglobulins (IgG, IgA, IgM) did not show a parallel drop and remained normal throughout the whole study. Our GH-deficient patients did not show any undue susceptibility to infections and our data thus seem to confirm that the immune function is basically intact in these children and that it is not suppressed by GH treatment. Although a drop in B lymphocytes was observed, the normal level of immunoglobulins and the normal functional response to PWM seem to demonstrate the maintenance of a normal humoral immune response.     

Growth Hormone Response to Overnight Growth Hormone-Releasing Hormone Infusion and Oral Pyridostigmine in Children with Short Stature

Ross, R.J.M., Savage, M.O., Kirk, J.M.W. and Besser, G.M. (Departments of Endocrinology and Child Health, St Bartholomew's Hospital, London, UK). Growth hormone response to overnight growth hormone-releasing hormone infusion and oral pyridostigmine in children with short stature. Acta Paediatr Scand [Suppl] 349: 114, 1989.
The development of a long-acting or depot preparation of growth hormone-releasing hormone (GHRH) may have many advantages over conventional treatment (with GH) of GH-deficient children. Pyridostigmine, an acetylcholinesterase inhibitor, has been shown to augment basal GH secretion and the GH response to GHRH in short children. It may thus provide adjuvant therapy to depot GHRH. The GH response to a nocturnal subcutaneous infusion of GHRH (1–29)NH₂ in doses of 5 and 10 pg/kg/hour was investigated in five short, slowly growing children. The effect of oral pyridostigmine 60 mg on nocturnal GH secretion and the GH response to a nocturnal infusion was also examined. The subcutaneous infusion of GHRH augmented pulsatile GH release in all five children. There was a dose-related response to subcutaneous GHRH for the GH area under the curve and mean GH pulse amplitude, but no change in the number of pulses. There was a significant rise in the mean baseline GH concentration during the GHRH infusion compared with placebo. Pyridostigmine had no effect on either basal or stimulated GH secretion.     

Growth Hormone Secretion and Growth Hormone Treatment in Children with Intrauterine Growth Retardation

Albertsson-Wikland, K. (Departments of Paediatrics II and Physiology, University of Gothenburg, Gothenburg, Sweden). Growth hormone secretion and growth hormone treatment in children with intrauterine growth retardation. Acta Paediatr Scand [Suppl] 349: 35, 1989.
Few children with intrauterine growth retardation (IUGR) fail to show catch-up growth during the first year of life. There may he many reasons for this, ranging from disturbances of hormone production to hormonal unresponsiveness of target cells. This report presents preliminary data on growth hormone (GH) secretion and responses to GH treatment in 16 children with IUGR and poor catch-up growth, six of whom had Silver-Russell stigmata. GH secretion was assessed by measurement of the GH response to an arginine-insulin test and determination of spontaneous GH secretion over 24 hours. GH production was heterogeneous hut, more often than expected, children showed both a low response to GH provocation and low spontaneous secretion of GH. Five out of six of the children with Silver-Russell syndrome and seven out of 10 of the children with non-Silver-Russell IUGR gained more than 2 cm in height during 1 year of treatment with GH at a dose of 0.1 IU/kg/day. These results clearly demonstrate that some children with IUGR and poor catch-up growth secrete insufficient amounts of GH, and that many of these very short children show an improvement in growth rate during treatment with physiological doses of GH.     

Noonan's Syndrome: Abnormalities of the Growth Hormone/IGF-I Axis and the Response to Treatment with Human Biosynthetic Growth Hormone

ABSTRACT. Auxological and endocrine data from 6 children (3 male, 3 female) aged 8.5–12.8 years with Noonan's syndrome and the results of treatment with human biosynthetic growth hormone (hGH) are presented. All the children were short (Ht SDS -3.5 to -2.3) and height velocity SDS ranged between -1.76 and +0.03. The maximum plasma growth hormone (GH) response to standard provocation tests ranged from 17 to 52 mU/l, yet, plasma insulin-like growth factor I (IGF-I) concentrations were low or low normal. Overnight GH secretory profiles were normal in all but 2 children who had disordered pulsatility with high trough concentrations. In 5 children who have completed one year of hGH therapy mean height velocity increased from 4.8 to 7.4 cm/year and the height velocity SDS ranged from +0.2 to +3.75. This improvement was associated with an increase in plasma IGF-I in three subjects. These results suggest that a defect of the GH/IGF-I axis may be present in some children with Noonan's syndrome and hGH therapy may have a role in the management of the short stature in these children.     

Dramatic Early Postnatal Growth Failure in Children with Early Onset Growth Hormone Deficiency

From the large group of patients included in the Kabi Pharmacia International Growth Study, 58 were studied who were treated with growth hormone (GH) before the age of 2 years, after diagnosis of GH deficiency (GHD). The growth parameters calculated from these infants indicate dramatic early postnatal growth failure, thus suggesting that GH could participate in early postnatal growth. The intensity of growth failure in these infants with GHD suggests that early screening on clinical grounds is possible.     

Quality of Life Assessment Before and After Growth Hormone Treatment in Adults with Growth Hormone Deficiency

McGauley, G.A. (Department of Medicine, United Medical and Dental Schools of Guy's and St Thomas's Hospitals, St Thomas's Hospital, London, UK). Quality of life assessment before and after growth hormone treatment in adults with growth hormone deficiency. Acta Paediatr Scand [Suppl] 356: 70, 1989.
The effect of recombinant human growth hormone (rhGH) treatment on the quality of life w'as studied in adults with growth hormone deficiency (GHD). Twenty-four adults who satisfied strict criteria for GHD took part in a double-blind, placebo-controlled, 6-month trial.'Quality of life'assessment was performed at entry into the trial and after 1 month and 6 months, by means of self-rating questionnaires. Entry data were also compared with a control group of healthy subjects matched for age, gender, ethnic origin, socio-economic class and area of residence. Significantly lower scores on'quality of life'assessment in the growth hormone (GH) deficient patients were reported at entry into the trial compared with matched controls, indicating that patients with GHD may be psychologically compromised. Preliminary analysis of the results shows that after 6 months patients receiving human growth hormone (hGH) treatment experienced less perceived illness than the placebo group. Significant psychological improvement was noted in the hGH-treated patients'perception of their energy level and mood compared to the placebo group.     

生长激素缺乏儿童血清胰岛素样生长因子-1和瘦素水平的变化及其相互关系

目的探讨生长激素缺乏(GHD)儿童血清胰岛素样生长因子1(IGF1)、瘦素水平的变化。方法用放射免疫法分别检测20例正常青春期前儿童和23例GHD患儿血清IGF1和瘦素的水平。结果GHD组血清IGF1水平(51.158±29.988)μg/L低于对照组(112.680±41.540)μg/L,两者有显著差异(t=5.619P<0.01);瘦素水平(6.002±2.204)μg/L高于对照组(4.523±2.204)μg/L,两者比较有显著差异(t=2.225P<0.05);但IGF1和瘦素之间无相关性(P>0.05)。结论IGF1和瘦素对GHD患儿生长发育的调节作用是相互独立的。     

Parental Heights of Children with Idiopathic Growth Hormone Deficiency: Analysis from the Kabi International Growth Study

International Board, Kabi International Growth Study (Kabi, Stockholm, Sweden). Parental heights of children with idiopathic growth hormone deficiency: analysis from the Kabi International Growth Study. Acta Paediatr Scand [Suppl] 356: 178, 1989.
In an international study of children treated with growth hormone (GH), parental heights of 554 children with idiopathic growth hormone deficiency (IGHD) and of 248 children with secondary or'organic'growth hormone deficiency (OGHD) were ascertained. The maternal height SDS of IGHD children was -0.41 ± 1.26 (mean ± SD) and the maternal height SDS of OGHD children was 0.03 ± 1.11 ( p < 0.006). Paternal height SDS of IGHD children was -0.19 ± 1.08, and paternal height SDS of OGHD children was 0.15 ± 1.08 ( p < 0.006). Adverse deliveries were associated with significantly shorter mothers ( p = 0.04) and a greater discrepancy between paternal and maternal heights ( p < 0.006).     

Infancy Growth Pattern Related to Growth Hormone Deficiency

ABSTRACT. Linear growth during the first three years of life can be represented mathematically in terms of the "ICP-growth model", using a combination of a quickly decelerating Infancy component with the addition of a slowly decelerating Childhood component, the latter acting from the second half of the first postnatal year. The growth pattern for supine length of four children with growth hormone (GH) deficiency is related here to the first two components of this growth model. Basically, all four infants displayed a pattern in line with the exponential shape of the Infancy component to the age when GH therapy was initiated. This observation indicates the existence of the Infancy component as it has been adopted for the ICP-model, and also that it represents the part of postnatal linear growth which seems to be independent of GH. The onset of the Childhood component in healthy subjects has been observed as an abrupt increase in growth rate during the second half of the first year of life. A similar abrupt increase was observed in this study at the time of the initiation of GH therapy (16–27 months). This observation gives some further empirical support to the hypothesis that the child's age at onset of the Childhood component defines the as yet undetermined age at which GH begins to exert a significant influence on linear growth. ICP-based growth charts provide an improved instrument for early detection of GH deficiency.