Effectiveness of growth hormone (GH) therapy in GH-deficient children and non-GH-deficient short children

The growth response during short-term growth hormone (GH) treatment was evaluated in eight prepubertal non-GH-deficient (non-GHD) children and compared with six prepubertal GH-deficient (GHD) patients. Standard doses of GH can improve growth rate in GHD and in some non-GHD patients. In neither group the growth response can be predicted by the acute increase in Thymidine Activity or Somatomedin-C levels. A diagnostic trial of GH treatment may be the only certain method of selecting the short non-GHD patients who may benefit from long-term GH therapy.Abbreviations GH growth hormone - GHD growth hormone deficient - Sm-C somatomedin C - TA thymidine activity     

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目的探讨重组人生长激素(recombinant human growth hormone,rhGH,简称GH)治疗生长激素缺乏症(growth hormone deficiency,GHD)患儿效果及影响因素,建立GH治疗效果预测模型。方法回顾性分析1996年8月至2010年9月首都儿科研究所生长发育门诊确诊为GHD和多垂体功能低下(multiple pituitary hormonedeficiency,MPHD)且接受规范GH治疗的矮身材患儿115例临床资料,采用2009年卫生部最新颁布的中国儿童体格发育标准对儿童身高、体重进行标化,标准差计算采用国际公认的LMS方法。以治疗过程中的身高标准差分值变化(delta in height SDS,ΔHtSDS)和生长速度(growth velocity,GV)为效果评价指标,进行疗效和影响因素分析。用多元回归方法以75例治疗满1年且随访较规律者为模型人群,建立治疗效果预测模型。同时前瞻性随访15例规范治疗的GHD患儿为模型验证对象,对模型进行验证。结果患儿治疗第1年身高平均增长(10.56±2.83)cm,ΔHtSDS升高0.93±0.52;治疗前3个月的ΔH...     

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.     

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.     

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.     

Chemotherapy-induced growth hormone deficiency in children with cancer

Background. Chemotherapy (CT) may produce growth impairment, however, the pathogenesis is still unclear. Methods. A series of 25 patients mean age 13.3 years (6.3–19.8), previously treated for malignant solid tumours with only CT and surgery were studied. Growth hormone (GH) reserve was assessed by two different provocative stimuli (Clonidine and L-Dopa). Mean time between completion of treatment and GH evaluation was 18.5 months (2–74 months). At that time, all patients were in complete remission. Results. GH deficiency (GHD), defined by an impaired GH response to both provocative tests was observed in 11 out of 25 patients (44%). At diagnosis, mean standing height was +0.23 ± 1.42 SDS in the GHD group (GHD-g) and +0.18 ± 1.23 SDS in the non-GHD group (n-GHD-g). At the end of therapy, the mean standing height in the GHD-g was ?0.31 ± 1.22 SDS and ?0.17 ± 1.41 in the n-GHD-g, differing from the former group (P = 0.05). For a mean follow-up of 30 months from the end of treatment, the mean standing height was ?0.48 ± 1.23 SDS in the GHD-g and ?0.24 ± 1.51 SDS for the n-GHD-g (P = 0.03). Growth rate at the end of treatment was +0.13 ± 1.54 in the GHD-g and +0.21 ± 1.75 in the n-GHD-g. For a mean follow-up of 30 months from the end of treatment, the growth rate was different between GHD-g and n-GHD-g (?0.31 ±2.72 vs. ?0.21 ± 1.93, P < 0.05). Conclusions. 1) Growth impairment in children treated because of malignant diseases has a multifactorial etiology, but CT-induced GH deficiency is one potential adverse factor. 2) An endocrine follow-up should be introduced in order to detect and treat hormonal deficiencies as early as possible. © 1995 Wiley-Liss, Inc.     

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.     

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??Objective??To describe height velocity in pre-pubertal Growth Hormone Deficiency??GHD?? children without recombinant human growth hormone??rhGH?? treatment and explore the height velocity targets for the first year in response to rhGH treatment. Methods??Analyze retrospectively the height velocity data without??HV0?? and one year after ??HV1?? rhGH treatment in physiologic dose??0.7 U/??kg·w???? in pre-pubertal GHD children above 3 years old who were diagnosed from Jan??2000 to Dec??2009 in our hospital. The GHD patients who were included for calculation of HV0 had peak GH value in GH provocative test less than 7 ng/ml. HV0 was calculated according to age??HV0-CA??342 patients?? and bone age??HV0-BA??257 patients?? respectively. According to the peak GH value in GH provocative test??the patients who were included for calculation of HV1 were divided into GHD-1 group????0.33 nmol/L??140 patients?? and GHD-2 group??7.0??9.9 μg/L??33 patients??. Results??Within every bone age group??GHD-1 group had significantly higher HV1 than GHD-2 group??P??0.05????11.0??10.5-11.5?? cm/a??n??34?? vs. 9.9??9.1-10.8?? cm/a??n??6?? when bone age was less than 3 years??10.4??9.8-10.9?? cm/a??n??48?? vs. 8.8??8.3??9.2?? cm/a??n??8?? when bone age was between 3 to 5 years??and 9.5??9.1-9.9?? cm/a??n??58?? vs. 8.5??8.0-9.1?? cm/a??n??19?? when bone age was between 6 to 10 years. The mean HV1 of GHD-2 was very close to the 25th percentile??P25?? of GHD-1 group. They both were significantly higher than HV0-BA. Conclusion??The recommended height velocity target for the first year after rhGH treatment in pre-
pubertal GHD children is the P25 of HV1 of GHD-1 group. It should be at least 9.9 cm/a??8.7 cm/a and 8.3 cm/a when the bone age is less than 3 years??3 to 5 years and 6 to 10 years?? respectively.     

Evaluation of growth hormone secretion after completion of therapy

BACKGROUND: Growth hormone (GH) reserve in young adults previously diagnosed as having GH insufficiency, who were treated with human (h)GH replacement in childhood needs confirmation in adulthood. METHODS: Nine patients (seven males, two females; two empty cella, one hypoplasia of the hypophysis and six with idiopathic GH deficiency) diagnosed as having GH insufficiency by the insulin tolerance test (ITT) and dopamine stimulation test in childhood (mean age 12.8+/-2.6 years) were retested at completion of linear growth (mean age 21.0+/-3.0 years), 4.6+/-1.6 years after discontinuation of hGH therapy. RESULTS: At the initial diagnosis, seven had complete and two had partial GH deficiency. At diagnosis, the mean peak GH response to ITT and dopamine was 4.8+/-4.08 and 3.4+/-2.9 mU/L, respectively. At retesting, the mean GH response to ITT and dopamine stimulation was 3.5+/-2.5 and 3.3+/-3.1 mU/L, respectively (P=0.91 and 0.96, respectively). During hGH therapy, mean height velocity increased from 3.5+/-1.9 cm/year at diagnosis to 9.9+/-3.64 cm/year during the first year (P=0.002). One of nine children diagnosed as having GH insufficiency who was treated with hGH replacement had normal growth hormone secretion at completion of linear growth. CONCLUSIONS: All GH-insufficient children should be retested after completion of their hGH treatment and linear growth to identify those who are truly GH insufficient and who may benefit from GH therapy in adulthood.     

Prediction of growth response in prepubertal children treated with growth hormone for idiopathic growth hormone deficiency

Several multiple regression models have been developed to predict the first-year growth response to human growth hormone (hGH) in children with growth hormone deficiency (GHD). It was the aim of this study to analyse the significance of various growth parameters for a height prediction model. Data from 148 prepubertal children with idiopathic GHD were evaluated. The prediction model was developed by means of univariate and stepwise linear regression analysis and an “all possible” regression approach using Mallow's C(p) statistics. Six out of eight selected variables had a significant influence on the first-year growth rate. The most important parameter was the difference between target height SDS and height SDS at the start of therapy (THSDS - HSDSC0), accounting for 23.95% and 25.74% of the variability. No other single variable or combination of variables was more informative than the variable THSDS - HSDSC0 alone. From these data, growth velocity for the first year of hGH treatment was estimated as 1.106 (THSDS - HSDSC0) + 6.8 cm/y ± 2.2 cm (SE), allowing a prediction for different intervals between THSDS and HSDSC0. This equation was validated in a small group of 18 GHD patients demonstrating a predicted vs. observed first-year growth rate of 9.4 ± 1.1 vs. 9.5 ± 2.6 cm/y. We conclude that the difference between THSDS and height SDS at the start of therapy is an important predictor of the first-year growth response in children treated with hGH for idiopathic GHD. Unlike in previous studies, additional parameters did not increase predictability.     

Who is Treated with Growth Hormone Today?

ABSTRACT. The present demographic data from the Kabi International Growth Study (KIGS) database are summarized. Of the 2580 patients included, 85% have growth hormone deficiency (GHD) and 15% have other causes of growth failure. Idiopathic GHD is present in 78.5% of the patients, the remaining 21.5% have organic GHD. Isolated GHD is common in idiopathic GHD whereas multiple pituitary hormone deficiencies occur in at least 50% of the organic GHD patients. A preponderance of boys is observed in most groups of patients. Median chronological age (CA) at start of treatment is 10 years and median duration of therapy is 2.3 years. However, a wide range is observed. In most cases growth retardation is severe. In most patients with GHD height SDS for chronological age at start of therapy is at or below -3. The median difference between idiopathic and organic GHD is 1 SDS. Most patients have 6 or 7 injections of growth hormone (GH) per week. The median total weekly dose is approximately 0.5 IU/kg/week, but it is lower in older patients. It is concluded that steadily increasing numbers of patients with idiopathic and organic GHD are being treated with human GH (hGH). In addition, many patients with other growth disorders not necessarily associated with GHD receive hGH therapy. Chronological age at start of treatment still appears to be (too) high in most patients and growth retardation severe. The frequency of hGH injections has been increased to nearly daily administration. However, the total weekly dose appears to be low, especially in the older patients. It is hoped that KIGS will contribute to improving the efficacy of treatment and hence the quality of life for all patients with growth disorders.     

Growth Response to Human Growth Hormone Treatment in Children with Partial and Total Growth Hormone Deficiency

ABSTRACT. The growth response during the first and second years of human growth hormone (hGH) treatment was studied in 14 prepubertal children with so-called "partial" GH deficiency (peak GH between 8 and 15 mU/1) and compared to 28 prepubertal children with "total" GH deficiency (peak GH less than 8 mU/1). There was no difference in growth acceleration between children with partial and total GH deficiency, when initial covariables were taken into account. In a stepwise multiple regression analysis initial stature, pre-treatment growth velocity and skinfold thickness were shown to be most related to growth response, but after exclusion of 3 children with a genetic form of total GH deficiency and partial TSH deficiency this relationship was lost. GH levels during provocation tests and auxological criteria have a poor predictive value for growth response to hGH therapy.     

Growth hormone (GH) provocation tests and the response to GH treatment in GH deficiency.

OBJECTIVE: To identify factors, particularly the growth hormone (GH) provocation test result, affecting growth response to GH treatment in children with GH deficiency (GHD). SUBJECTS: A total of 337 prepubertal GHD patients aged <10 years from the UK Pharmacia KIGS database (GH response to provocation test <20 mU/l). OUTCOME MEASURE: Annual change in height standard deviation score (SDS) (revised UK reference) in the first and second years of treatment. RESULTS: Height increased by 0.74 SDS units (SD 0.39) in the first year of treatment and 0.37 units (SD 0.27) in the second. Adjusting for age, height, weight, midparent height, and injection frequency, the strongest predictor of first year growth response was the GH provocation test result; halving the result predicted an extra height increment of 0.09 units (p<0.0001). It predicted the second year response less well (p<0.0002) and after adjusting for the first year response was not predictive at all. CONCLUSIONS: Among patients referred for possible GHD, the GH provocation test, though not a gold standard for diagnosis, is a valuable predictor of growth response in the first year of treatment. A year's treatment is recommended for cases with a marginal provocation test result, with the option to continue treatment if the response is adequate. The value of unified protocols for single or repeated provocation tests needs to be assessed.     

Therapeutic Efficacy and Safety of GH in Japanese Children with Down Syndrome Short Stature Accompanied by GH Deficiency

In this study, we investigated the effects of GH treatment in children with Down syndrome who had been diagnosed with GH deficiency (GHD). A total of 20 subjects were investigated in this study. Fourteen Down syndrome children (5 boys and 9 girls) with short stature due to GHD were treated with GH at Okayama Red Cross General Hospital, and 6 Down syndrome children (4 boys and 2 girls) with short stature due to GHD were registered in the Pfizer International Growth Database (KIGS). Height SD score (SDS) increased throughout the three-year GH treatment period. The overall mean height SDS increased from –3.5 at baseline to –2.5 after 3 yr of treatment. The mean change in height SDS during these 3 yr was 1.1. In addition, height assessment of SD score based on Down syndrome-specific growth data in the Japanese population revealed that the height SDS (Down syndrome) also increased across the 3-yr GH treatment period. The mean change in height SDS (Down syndrome) during these three years was 1.3. GH therapy was effective for Down syndrome short stature accompanied by GHD, and no new safety concerns were found in this study.     

Growth hormone therapy

Growth hormone (GH) therapy has revolutionized treatment of children with growth hormone deficiency (GHD). Improved height outcome with final height in the target height range has been achieved in these children. Identification of Creutzfeldt-Jakob disease, a deadly prion mediated disorder, in recipients of pituitary GH accelerated the transition from pituitary derived GH to recombinant GH. Once daily subcutaneous administration of the freeze-dried preparation at evening is the recommended mode of GH therapy. Studies have led to use of higher dose of GH for improving height outcome (0.33 mg/kg/week or 0.14 IU/kg/day) albeit at a significantly high cost. Growth velocity increases from 3–4 cm/year before therapy to 10–12 cm/year during the first two years of therapy and is maintained at 7–8 cm/year after a period of two years. Close follow-up with regular clinical and laboratory monitoring is essential for achieving a desirable height outcome. A theoretical unlimited supply has led to wide spread use of GH in a variety of disorders other than GHD. Initially started in children with Turner syndrome, GH has now been used in chronic renal failure, idiopathic short stature and intrauterine growth restriction besides a wide array of newly emerging indications.     

Growth hormone (GH) provocation tests and the response to GH treatment in GH deficiency

Objective: To identify factors, particularly the growth hormone (GH) provocation test result, affecting growth response to GH treatment in children with GH deficiency (GHD). Subjects: A total of 337 prepubertal GHD patients aged <10 years from the UK Pharmacia KIGS database (GH response to provocation test <20 mU/l). Outcome measure: Annual change in height standard deviation score (SDS) (revised UK reference) in the first and second years of treatment. Results: Height increased by 0.74 SDS units (SD 0.39) in the first year of treatment and 0.37 units (SD 0.27) in the second. Adjusting for age, height, weight, midparent height, and injection frequency, the strongest predictor of first year growth response was the GH provocation test result; halving the result predicted an extra height increment of 0.09 units (p<0.0001). It predicted the second year response less well (p<0.0002) and after adjusting for the first year response was not predictive at all. Conclusions: Among patients referred for possible GHD, the GH provocation test, though not a gold standard for diagnosis, is a valuable predictor of growth response in the first year of treatment. A year''s treatment is recommended for cases with a marginal provocation test result, with the option to continue treatment if the response is adequate. The value of unified protocols for single or repeated provocation tests needs to be assessed.     

Growth Hormone Treatment in Non-Growth Hormone-Deficient Children: Effects of Stopping Treatment

ABSTRACT. Overnight physiological growth hormone (GH) secretion was evaluated in 95 short, prepubertal children (73 boys, 22 girls). All the children were below the 3rd centile for height and achieved CH levels greater than 15 mU/1 following pharmacological stimulation. The mean average GH level was 7.1 mU/l and the mean sum of pulse amplitudes 80.4 mU/l. No relationship was found between age, height or height velocity and any of the parameters of GH secretion. The group was randomized to receive placebo, GH or remain under observation for the first 6 months and then all patients received GH treatment for a further 6 months. Those treated with GH, 0.27 IU/kg (0.1 mg/kg) three times weekly, in the first phase. demonstrated a mean increase in height velocity SDS of 3.24. There was no difference in growth response between the placebo or observation groups. In the second 6-month period. all children received GH according to the same dose regimen: they were then observed for a further 6 months following its discontinuation. In the 6 months following withdrawal of GH, all groups showed a significant fall in height velocity SDS, which returned to pretreatment levels, without demonstrating'catch-down'growth. Repeat sampling of overnight GH secretion within 3 days of discontinuing GH showed normal secretory patterns with a small reduction in mean peak amplitude. These results suggest that short children without classic GH insufficiency respond well to exogenous GH in the short term and return to pretreatment height velocities afterwards. Consequently, it may be possible to increase final adult height in such children by GH treatment.     

Growth hormone therapy in Silver Russell Syndrome: 5 years experience of the Australian and New Zealand Growth database (OZGROW)

Data were analysed on 33 children (22 males) with Silver Russell syndrome treated with growth hormone for periods up to 5 years. Baseline data (medians) at commencement of growth hormone (GH) therapy were age 6.7 years, bone age delay 1.7 years, height standard deviation score (SDS)-3.2, weight SDS –3.1, and growth velocity 5.7 cm/ year. All were prepubertal. Median birth weight SDS for gestational age was –3.2. GH was commenced at 14 IU/m² per week and subsequently adjusted according to response. Growth velocity and growth velocity SDS for chronological age (CA) improved over baseline and gains in height SDS for CA were 1.0, 1.5 and 1.8 SD over 3, 4 and 5 years respectively (P < 0.001). No significant increase in height SDS for bone age was observed. Increased GH doses were required after the 1st year to maintain growth rates. Mean bone age advancement was 3.1 years after 3 years of treatment, and 6.0 years after 5 years treatment. Younger age was a predictor of the growth response over the 1st year. Predictors of response after 3 years were catch-up growth, low weight SDS at birth and low height SDS for CA. Age at onset of puberty was normal, but height at onset of puberty was lower than normal means. Conclusion We have demonstrated significant improvement in growth in Silver Russell syndrome after 3 years of GH therapy, however data on estimated mature height and final height are insufficient to conclude final outcomes. Further follow up is required to assess the long-term benefit. Received: 19 July 1995 Accepted: 4 March 1996     

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。     

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.