Multicentric study of efficacy and safety of growth hormone use in growth hormone deficient children in India

Growth Hormone being very expensive in India data on use of recombinant human growth hormone (rhGH) is scarce. The authors studied the effect and safety of one year of therapy with rhGH on growth velocity and predicted final height in Indian patients with growth hormone deficiency (GHD). A multicentric, prospective, open trial with rhGH was performed on 15 patients. Patients received rhGH in a dose of 0.7 IU (0.23 mg)/Kg/week. The mean pretreatment height was 111.2cms {SD 12.4}, height velocity was 3.1 cms per year {1.2} and predicted height was 146.5 cms {10.4} at a mean age of 12.0 (2.8). At the end of therapy mean height was 123.4 {11.9}, height velocity was 12.1 cms per year {2.8} and the predicted height was 153.0 cm {9.4}. The increase in predicted height was thus 6.5cm (4.2). The increment in height velocity with growth hormone therapy was statistically significant (p value= 0.001). The present study shows that children with growth hormone deficiency in India also benefit from therapy with rhGH even when treatment is started late as compared to the published Western data and there is a potential for increased final height.     

长效促性腺激素释放激素类似物和甲孕酮治疗对真性性早熟女孩预测身高影响的比较

目的观察促性腺激素释放激素类似物（ＧｎＲＨａ）和甲孕酮用于治疗真性性早熟女孩,对其抑制性发育,减慢骨成熟和生长速度,改善成人期预测身高的作用。方法分别使用两种药物治疗两组特发性真性性早熟女孩各９例,时间６～１２个月,观察治疗前后的身高、性发育情况、骨龄、成人期预测身高等,并进行综合比较。结果两组患儿经治疗后,性发育情况大多数得到抑制。甲孕酮治疗组骨龄年增长为１１岁,身高年增长为７６ｃｍ,成人期预测身高治疗前后无改变。长效ＧｎＲＨａ组骨龄年增长为０２岁,身高年增长为５６ｃｍ,成人期预测身高治疗６个月时增长３１ｃｍ,较治疗前明显改善（Ｐ＜００１）,治疗１年时增长６４ｃｍ,较治疗６个月时更为明显（Ｐ＜００５）。结论长效ＧｎＲＨａ与甲孕酮相比较,除可抑制性发育进程外,还可有效减慢骨成熟和生长速度,最终改善成人期预测身高,治疗时间愈长,效果愈明显     

Growth hormone treatment in Turner syndrome accelerates growth and skeletal maturation

Sixteen girls with Turner syndrome (TS) were treated for 4 years with biosynthetic growth hormone (GH). The dosage was 4IU/m² body surface s.c. per day over the first 3 years. In the 4th year the dosage was increased to 61 U/m² per day in the 6 girls with a poor height increment and in 1 girl oxandrolone was added. Ethinyl oestradiol was added after the age of 13. Mean (SD) growth velocities were 3.4 (0.9), 7.2 (1.7), 5.3 (1.3), 4.3 (2.0) and 3.6 (1.5) cm/year before and in the 1st, 2nd, 3rd and 4th year of treatment. Skeletal maturation advanced faster than usual in Turner patients especially in the youger children. Although the mean height prediction increased by 5.6 cm and 11 of the 16 girls have now exceeded their predicted height, the height of the 4 girls who stopped GH treatment exceeded the predicted adult height by only 0 to 3.4 cm.     

Comparative effect of two doses of growth hormone for growth hormone deficiency. The Dutch Growth Hormone Working Group.

The comparative effect and safety of 2 IU compared with 4 IU/m2/day of recombinant human growth hormone (rhGH) was studied in 38 growth hormone deficient children regarding the impact of several factors on short term (one year) and long term (three year) growth response. In 21 newly diagnosed patients, three years of rhGH treatment resulted in a significant increase of height velocity SD score, height SD score, and predicted adult height SD score, irrespective of rhGH dose. In 17 transfer patients (previously treated with 12 IU rhGH/m2/week) 4 IU/m2/day resulted in a significantly higher height velocity SD score and height SD score for chronological age than 2 IU/m2/day, while more of them reached their target range or showed a substantial height SD score increment. Height SD score for bone age and predicted adult height SD score only increased significantly with 4 IU rhGH. After one year of rhGH treatment, new patients showed significant negative correlation between delta height SD score with age and baseline insulin-like growth factor I (IGF-I) SD score, and positive correlation with rhGH dose. After three years of treatment, delta height SD score for chronological age was significantly, negatively correlated with age and baseline 'corrected' height SD score (height SD score for chronological age minus target height SD score). There was no significant correlation with rhGH dose. Prolonged treatment with either dose had no adverse effect on IGF-I concentrations, carbohydrate or lipid metabolism. As early age and divergence between height SD score and target height SD score seem more important for growth response than rhGH dose, it is recommended that treatment starts early with 2 IU rhGH/m(2)/day and the dose is doubled if growth is insufficient after several years of treatment.     

重组人生长激素治疗生长激素缺乏症疗效观察

目的 观察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15例GHD患儿应用rhGH治疗,每晚睡前皮下注射0.1 IU/kg,疗程6个月。结果 患儿身高由治疗前109.3±9.9cm增加到115.5±11.3 cm;年身高生长速度由治疗前2.8±0.6cm/年增加到11.6±3.5cm/年。治疗期间除少数患儿出现亚临床甲状腺功能低下,注射部位有轻度反应外,未发现明显副作用。结论 皮下注射rhGH是治疗儿童GHD的一种安全有效的方法。     

Impact of growth hormone treatment on a Belgian population of short children with renal allografts

We retrospectively analyzed the effects of recombinant human growth hormone (rhGH) in a Belgian population of 36 short children with renal allografts. Seven children were dropped from the growth study: 1 had skeletal dysplasia and in 6 cases rhGH was given for less than 1 yr (1 died, 1 developed genu valgum, 2 were non-compliant and 2 grafts deteriorated). Final height was reached in 17 patients, and 12 children were still growing at the end of the study. Median height standard deviation score (SDS) in the 29 patients was -2.3 at the time of transplantation, and -2.7 when rhGH therapy was initiated. During rhGH therapy (median duration 3.2 yr, range 0.6-7.7 yr), height SDS increased by a mean of 0.4 per year, and bone maturation was not accelerated. Final height reached was 162.7 (149.0-169.5) cm (median SDS -1.8) in males and 151.0 (130.5-169.5) cm (median SDS -1.9) in females. Final height is significantly greater in males than females compared with a historical control group of untreated patients. Final height is within the parental target height range in 6 out of the 17 patients. The increase in height SDS in patients who were at an advanced stage of puberty (Tanner stages 4-5) when rhGH therapy was initiated exceeded our expectations (mean height gain 14.2 cm in boys and 10 cm in girls). In the cohort of 36 children, 4 patients developed an acute allograft rejection, all of whom had an underlying chronic rejection. This resulted in 3 graft losses within 5 yr. Our results indicate that rhGH treatment has a positive effect in short children with renal allografts, even if it is started in late puberty. In the presence of underlying chronic rejection, rhGH treatment needs careful monitoring to minimize the risk of graft loss.     

重组人生长激素治疗特发性矮小12个月疗效评估

目的 分析重组人生长激素(rhGH)对特发性矮小（ISS）患儿的治疗效果和影响因素,为寻求优化治疗效果的途径提供参考依据。 方法 回顾性分析2003年2月至2011年7月在首都儿科研究所生长发育门诊确诊为ISS患儿的临床资料,依据是否予rhGH治疗分为rhGH组和对照组。以身高标准差变化（ΔHtSDS）和生长速度（GV）作为评估指标进行疗效和影响因素分析。分析治疗期间骨龄、身高年龄及胰岛素样生长因子(IGF-1)水平的变化。 结果 rhGH组35例,对照组33例进入分析。①rhGH组治疗前、治疗后12个月HtSDS呈增长趋势(P<0.05);对照组均未见升高趋势。治疗后0～3个月的ΔHtSDS水平为(0.22±0.13),治疗后~6、~9和~12个月分别为(0.20±0.10)、(0.12±0.14)和(0.14±0.15),呈降低趋势,但差异无统计学意义。治疗后0～3个月GV为(10.78±2.70) cm·year-1,治疗后~6、~9和~12个月分别为(10.52±2.44)、(8.31±2.78)和(8.50±2.29) cm·year-1,呈降低趋势,但差异无统计学意义。治疗后0~6个月ΔHtSDS和GV水平均显著高于～12个月［ΔHtSDS :(0.43±0.20) vs (0.27±0.24), GV: (10.48±2.17) vs (8.48±2.39) cm·year-1］。②治疗后12个月的ΔHtSDS水平与治疗开始时的年龄呈负相关,与治疗后0～3个月的ΔHtSDS呈正相关;治疗后12个月的GV水平与治疗前的GH峰值和治疗后3个月的GV水平呈负相关。③治疗后1年青春期前、青春早中期和青春后期ΔHtSDS差异总体上有统计学意义（P=0.016）,其中青春期前显著高于青春早中期和青春后期;GV差异无统计学意义。④rhGH组治疗后12个月的骨龄变化差异无统计学意义,身高年龄显著高于对照组。⑤rhGH组IGF-1水平在治疗后1个月升高较明显,之后升高趋势减缓。 结论 rhGH用于ISS患儿的治疗应尽量选择青春期前;治疗后3个月的效果可作为第1年治疗效果的预测因素;rhGH治疗不会使ISS患儿骨龄明显提前。     

特发性矮小患儿生长激素受体基因Ex3多态性与重组人生长激素疗效分析

目的：观察生长激素受体（GHR）基因Ex3多态性与重组人生长激素（rhGH）治疗青春期前特发性矮小（ISS）疗效间的相关性。方法：青春期前ISS患儿30例,均采用rhGH［0.116±0.02 IU/(kg/d)］治疗;其外周血白细胞中抽提基因组DNA,采用多重PCR扩增GHR基因Ex3区域。对不同基因型患儿治疗后生长速率（GV）、年龄对应身高标准差积分（HtSDSCA）及骨龄对应身高标准差积分（HtSDSBA）、预测终身高进行比较。结果：rhGH治疗半年后d3/d3基因型组GV较fl/fl基因型组明显增加［（6.3±1.6）cm/年 vs （3.4±0.5）cm/年,P<0.05］。结论：ISS患儿GHR Ex3基因型与rhGH促生长疗效存在一定关联,d3/d3等位基因型患儿用rhGH治疗后生长速率明显优于fl/fl等位基因型。［中国当代儿科杂志,2010,12（9）：730-733］     

Growth hormone therapy in Turner's syndrome. Impact of injection frequency and initial bone age.

STUDY OBJECTIVE--To determine the influence of the injection frequency and the initial bone age on the efficacy of treatment with biosynthetic growth hormone in Turner's syndrome. DESIGN--Randomized study. SETTING--Referral-based pediatric endocrinology departments of seven university medical centers. PATIENTS--Fifty-two patients with Turner's syndrome confirmed with chromosomal analysis. TREATMENT--Somatotropin recombinant DNA (24 IU/m2 of body surface area) subcutaneously administered in three or six injections per week for 2 years. Patients who were older than 12 years at the beginning of the study received low doses of estrogen. RESULTS--The following statistically significant findings supported the use of six injections per week compared with three injections per week: the mean (+/- SD) increment in height during 2 years was 11.3 cm (3.8 cm) with six injections vs 8.6 cm (3.4 cm) with three injections; the increment in height standard deviation score was 0.9 cm (0.5 cm) vs 0.6 cm (0.3 cm); the growth velocity was 6.6 cm/y (2.0 cm/y) vs 5.2 cm/y (1.7 cm/y) in year 1 and 4.7 cm/y (2.0 cm/y) vs 3.4 cm/y (1.7 cm/y) in year 2; and the increment in height standard deviation score for bone age was 0.8 cm (0.5 cm) vs 0.4 cm (0.6 cm). For patients whose initial bone age was more than 13 years, growth velocity increased by 1 to 2 cm in year 1; in year 2 no increment was observed. We did not observe adverse effects. CONCLUSIONS--Biosynthetic growth hormone in a higher-frequency regimen in Turner's syndrome is more efficient in terms of increment in height, growth velocity, and height standard deviation score for bone age than treatment in a lower-frequency regimen. In patients with an initial bone age of more than 13 years, the response was poor. Longer follow-up is necessary to assess the effect on final height.     

Combined therapy with growth hormone and oxandrolone in adolescent girls with Turner syndrome

Five adolescent girls with Turner syndrome (mean age 13.9 years, mean bone age 12.0 years) were treated with both recombinant human growth hormone (rhGH) and oxandrolone for 2 years with an average increment in height of 13.4 cm. The mean bone age advanced by only 1.2 years, providing an increase in the mean estimated mature height of 9.2 cm. We conclude that rhGH and oxandrolone benefit older teenagers with Turner syndrome because of an increased growth rate with slow progression of skeletal maturation.     

Short-term therapy with recombinant growth hormone in polytransfused thalassaemia major patients with growth deficiency

Growth failure is commonly described in polytransfused thalassaemia major patients (Th) with or without growth hormone (GH) releasing hormone-GH axis impairment. We have investigated the efficacy of short-term recombinant GH (rhGH) therapy (Saizen [Serono] 0.1 IU/kg/day 6 evenings/week administered s.c. for 12 months) on growth and predicted final height in 28 (19M, 9F) regularly transfused Th with growth deficiency (aged 14.8 +/- 2.0 yr) on long term desferrioxamine s.c. therapy. All Th had no evidence of congestive heart failure, hypothyroidism or impaired glucose tolerance; in all patients the GH peak (evaluated during both insulin and clonidine test) was < or = 20 mIU/l; hypergonadotropic hypogonadism was excluded in Th with delayed puberty. At the start of therapy height age (HA)/bone age (BA) ratio was 0.92 +/- 0.12. Bone age delay was positively correlated to chronological age (CA), serum ferritin levels (mean of the last three years), the age at the start of chelation therapy, growth velocity calculated for CA during the last year; a positive correlation was also found between circulating IGF-I levels and age at the start of chelation therapy. After 1 year on rhGH therapy there was a significant increase of height calculated for CA (not for BA), of growth velocity calculated for both CA and BA and of circulating IGF-I levels; the HA variation/BA variation ratio was 1.85 +/- 1.71, without any significant difference between predicted final height at the start (-1.08 +/- 1.28 SDS) and at the end of rhGH therapy (-0.88 +/- 1.13). The variation of height calculated for CA was positively correlated to both CA and growth velocity during the last year before rhGH therapy (calculated for CA) and negatively to the height at the start (calculated for CA). There were no side effects and haematological parameters did not show significant changes. In conclusion, our data, obtained in a relatively large group of Th, confirm the emerging results of short-term (12 months) rhGH therapy on growth, as shown by the increase of both growth velocity and height calculated for CA. With regard to final height, although the mean variation of HA/variation of BA ratio was 1.85, no significant increase of the predicted final height was found between the start and the end of rhGH therapy. We are evaluating the effect of long-term rhGH therapy on growth in these patients.     

Effect of long-term recombinant growth hormone therapy in children--the National Cooperative Growth Study, USA, 1985-1994

Over a 9-year period (1985-1994) approximately 20,000 children received recombinant human growth hormone (rhGH) while enrolled in the National Cooperative Growth Study (NCGS), an observational, longitudinal study designed to monitor the long term efficacy and safety of rhGH administered to children in North America. Forty-four percent of the patients had idiopathic growth hormone deficiency (IGHD), 13.8% organic GHD (OGHD), 25% idiopathic short stature (ISS), 9.9% Turner's syndrome (TS), and 7.3% miscellaneous disorders. Eighty-five percent of the patients enrolled were Caucasian, and approximately two-thirds of the non-Turner patients were male. For the subset of patients treated for at least 4 years and who were prepubertal throughout this period (IGHD N=308, OGHD N=93, ISS N=169, TS N=82), mean growth rates increased in all patient categories and remained at or above pretreatment growth rates through 4 consecutive years of therapy with rhGH. Growth rates during administration of rhGH were greater in children in whom the pretreatment maximum stimulated GH concentration was < or =3 microg/l. Patients treated with 6 or 7 doses of rhGH each week grew more rapidly than did those receiving thrice weekly dosages, although the ratios of the increment in bone age to the increment in height age after two years of therapy were similar in the two treatment regimens. For patients treated with rhGH for 7 consecutive years, the mean height standard deviation scores increased by 2.5 in IGHD (N=169), 2.0 in OGHD (N=50), 1.9 in ISS (N=69), and 1.3 in TS (N=19), but remained below target heights in all categories. It is concluded that administration of rhGH increases growth rates in patients with IGHD, OGHD, ISS, and TS, and that this stimulatory effect can persist for at least 4 years.     

253例中国Turner综合征患者的自然生长曲线

目的制作中国人Turner综合征（TS）自然生长曲线。研究Turner综合征患儿自然生长规律。方法对全国5省市8所医院确诊的253例TS患者治疗前的身高、体重和骨龄进行观测。同一患者的2次测量值间隔至少超过1年才作为2例次参数计,共取得289个身高值和106个骨龄值。身高值经曲线参数估计法绘制曲线并与正常女孩生长曲线进行比较。结果患儿平均出生身长为(47.2±2.5)cm,身长标准差得分（HtSDS）为-1.52。3岁至13岁各年龄组患儿平均身高及其HtSDS值随年龄增大与正常值差距增大,HtSDS从3岁的-2.11降至13岁的-4.83,患儿平均身高与同年龄正常身高均数之差由3岁的8.03cm增加至13岁的27.89cm,从13岁起逐渐减少至20岁的18.87cm。成年身高为(140.0±7.9)cm。8岁前TS患儿生长曲线     

A controlled trial of methionyl growth hormone therapy in prepubertal children with short stature, subnormal growth rate and normal growth hormone response to secretagogues. Dutch Growth Hormone Working Group

Thirty short and slowly growing children with normal plasma growth hormone (GH) responses to standard provocation tests were randomly assigned to either a group (n = 20) undergoing treatment with methionyl GH (somatrem), 2 IU per m2 body surface s.c. daily, or a control group (n = 10). Twelve out of 18 children who completed the first year of treatment showed a height velocity increment of more than 2 cm/year. The mean (SD) growth velocity of the treatment group increased by 3.0 (1.9) cm/year over the first year, compared with -0.2 (0.7) cm/year in the control group. Neither parameters of endogenous GH secretion nor plasma IGF-I levels showed a significant correlation with the growth response. Of the auxological variables studied, pre-treatment growth velocity (r = -0.8) and the short-term height velocity increment (r = 0.7-0.9) showed significant correlations with the growth response in the first year of treatment. Somatrem therapy was without side effects, except in one child who developed anti-GH antibodies in combination with a poor growth response.     

Long-Term Results with a Slow-Release Gonadotrophin-Releasing Hormone Agonist in Central Precocious Puberty

ABSTRACT. As part of an ongoing international multicentre study, 19 children (14 girls, 5 boys) with central precocious puberty (CPP) were treated with a slow-release gonadotrophin-releasing hormone (GnRH) agonist, triptorelin, for 4 years. After 3 years of treatment, height velocity stabilized at 4.0 cm/year. Predicted adult height (mean ± SD) increased from 158.9 ± 6.8 to 164.9 ± 6.6 cm in girls (n = 14, p < 0.01), and from 174.4 ± 18.5 to 184.3 ± 17.1 cm in boys (n = 4, p < 0.05). In 12 additional girls who had started the multicentre study but discontinued triptorelin treatment after 2.2 ± 0.5 years, menses started 9.8 ± 3.7 months after cessation of treatment in all but one patient. Height velocity increased over the first 6 months after discontinuation of treatment, from 3.6 ± 0.1 to 5.4 ± 2.5 cm/year, and remained higher than pretreatment values in the second 6 months, but decreased subsequently. Bone maturation increased, and no significant improvement in predicted adult height was observed. For auxological reasons, therefore, it may be advisable to continue triptorelin treatment for as long as possible. Concomitant growth hormone (GH) therapy was initiated in three girls with CPP with height velocities of 3.2–3.6 cm/year after 3 years of treatment with triptorelin and predicted adult heights of less than the third centile for Dutch girls. Prior to the administration of GH, all patients had subnormal 24-hour GH profiles and GH responses to arginine provocation. GH treatment increased height velocity markedly in all girls, and improved predicted adult height. It is concluded that triptorelin therapy improves predicted adult height. In children with CPP and genetic short stature, with a markedly decreased height velocity during triptorelin therapy, concomitant administration of a GnRH agonist and GH may have advantages. Further extensive studies are required.     

The effect of oestrogen treatment on body proportions in constitutionally tall girls

Body proportions were studied in 31 girls with constitutional tall stature during treatment with 200 g ethinyl oestradiol per day continuously, combined with 5–10 mg medroxyprogesterone on the first 10 days of each month. Their mean (±SD) predicted adult height was 186.0 (±4.0) cm. At the start of therapy, leg length (LL) standard deviation score (SDS) (3.8±0.7) was significantly greater than the sitting height (SH) SDS (2.3±1.1). During therapy, the mean sitting height increased by 2.9 cm, in contrast to an increment of only 0.8 cm for LL. The SDS of the ratio between SH and LL remained below zero. The expected gain without therapy, assuming a stable SDS position over time, was 5.4 cm for SH and 4.4 cm for LL, significantly more than the observed gains. In conclusion, tall girls have relatively long legs. Oestrogen therapy leads to an almost complete stop of leg growth, while the growth of the trunk is reduced to a lesser extent. This selective inhibition results in a trunk/leg ratio which is closer to, though still significantly different from that of normal girls.     

A Controlled Trial of Methionyl Growth Hormone Therapy in Prepubertal Children with Short Stature, Subnormal Growth Rate and Normal Growth Hormone Response to Secretagogues

ABSTRACT. Thirty short and slowly growing children with normal plasma growth hormone (GH) responses to standard provocation tests were randomly assigned to either a group ( n = 20) undergoing treatment with methionyl GH (somatrem), 2IU per m² body surface s.c. daily, or a control group ( n = 10). Twelve out of 18 children who completed the first year of treatment showed a height velocity increment of more than 2 cm/year. The mean (SD) growth velocity of the treatment group increased by 3.0 (1.9) cm/year over the first year, compared with -0.2 (0.7) cm/year in the control group. Neither parameters of endogenous GH secretion nor plasma IGF-I levels showed a significant correlation with the growth response. Of the auxological variables studied, pre-treatment growth velocity ( r = 0.8) and the short-term height velocity increment ( r = 0.7–0.9) showed significant correlations with the growth response in the first year of treatment. Somatrem therapy was without side effects, except in one child who developed anti-GH antibodies in combination with a poor growth response.     

Methionyl human growth hormone in Turner's syndrome.

Sixteen girls with Turner''s syndrome aged 7.9-15.2 years (bone ages 7.0-11.8 years) were given methionyl growth hormone (somatrem) 4 IU/m2 body surface daily, corresponding to 0.9 IU/kg/week. During one year of treatment their mean (SD) height velocity increased from 3.4 (0.9) to 7.2 (1.7) cm/year and height prediction from 148.2 (4.4) to 150.0 (4.4) cm. All the girls except one had a height velocity increment of more than 2 cm/year and these velocities are above the age references for girls with Turner''s syndrome. The girl with a low growth response had antibodies against growth hormone with high binding capacity (3.7 U/l). The height velocity increment was inversely correlated with age and bone age, but this might be partly due to the somewhat higher dosage/m2 body surface and kg body weight that the younger patients were given because of the rounding off of the dose. The better results of our study compared with those of other workers who used similar dosages but did not give the drug as often suggest that giving it daily might have increased the growth response as it does in children deficient in growth hormone.     

Conjugated-estrogen treatment of excessively tall girls (author's transl)

46 excessively tall girls, aged 10.5-15 years and with a mean height prediction of 185.5+/-3.3 cm were treated with 7.5 mg conjugated estrogens daily and 5 mg gestagens daily for 5-10 days. Treatment for 30 girls has been completed. Bone age was assessed according to Tanner et al. taking into account midparent height. Mean bone-age was 13.0+/-0.6 years at the beginning and 15.5+/-0.6 years at the end of treatment. Duration of therapy was 19.6+/- 6.8 months and mean reduction of predicted height in all patients was 4.1+/-2.4 cm. Bone age subgroups do not alter the results. Bone maturation was accelerated by treatment to 1.8 years/year with marked acceleration during the first six months. Growth velocity was low during the 6th-12th month. Increase of growth was 1.4+/-1.2 cm in the second period of therapy, representing 50% of the initial phase. Side-effects were minimal. The results are in agreement with those reported in other comparable series.     

Effect of combined treatment with gonadotropin releasing hormone analogue and growth hormone in patients with central precocious puberty who had subnormal growth velocity and impaired height prognosis

Growth hormone-insulin-like growth factor-I status and response to growth hormone therapy (0.6 IU/kg/week sc, six times a week for 12 months) were evaluated in 12 girls (chronological age 9.4 ± 1.6 years) suffering from central precocious puberty with growth velocity less than 4 cm/year and no substantial increase or decrease in predicted adult height during gonadotropin releasing hormone (Gn-RH) analogue treatment (D-Trp⁶-LH-RH, 60 μg/kg im/28 days). At baseline, large variations were observed in nocturnal growth hormone (GH) means (pathological values (< 3.6μg/l) 33.3%), stimulated levodopa GH peaks (pathological values (<10.0 μg/I) 28.6%) and serum insulin-like growth factor-I (IGF-I) levels. Neither GH nor IGF-I levels were correlated with growth velocity. During recombinant GH therapy, growth velocity increased significantly (baseline 3.0 ± 0.9 cm/year; 6 months 6.4 ± 1.9cm/year, p < 0.001 versus baseline; 12 months 6.0 ± 1.3cm/year, p < 0.001 versus baseline). There was a significant increase in height SDS for bone age (baseline –1.6 ±0.5 SDS; 12 months -1.04 ± 0.6SDS; p < 0.002) and in predicted adult height (baseline 152.0 ± 3.6cm; 12 months 155.9 ± 3.4cm; p < 0.002). Our results suggest that combined therapy with Gn-RH analogues and recombinant GH can improve growth velocity and predicted adult height in girls with central precocious puberty and impaired height prognosis during Gn-RH analogue treatment.