Growth hormone treatment of short children born small for gestational age: metanalysis of four independent, randomized, controlled, multicentre studies

A minority of children born small for gestational age (SGA) fail to achieve sufficient catch-up growth during infancy and remain short throughout childhood, apparently without being growth hormone (GH) deficient. The effect of GH administration was evaluated over 2 years in short prepubertal children born SGA. The children ( n = 244), who were taking part in four independent multicentre studies, had been randomly allocated to groups receiving either no treatment or GH treatment at a daily dose of 0.1, 0.2 or 0.3 IU/kg (0.033, 0.067 or 0.1 mg/kg) s.c. At birth, their mean length SD score (SDS) was -3.6 and their mean weight SDS -2.6; at the start of the study, mean age was 5.2 years, bone age 3.8 years, height SDS -3.3, height SDS adjusted for parental height -2.4, weight SDS -4.7 and body mass index (BMI) SDS -1.4. The untreated children had a low-normal growth velocity and poor weight gain. Although bone maturation progressed more slowly than chronological age, final height prognosis tended to decrease, according to height SDS for bone age. GH treatment induced a dose-dependent effect on growth, up to a near doubling of height velocity and weight gain; BMI SDS was not altered. Bone maturation was also accelerated differentially; however, final height prognosis increased in all GH treatment groups. The more pronounced growth responses were observed in younger children with a lower height and weight SDS. In conclusion, GH administration is a promising therapy for normalizing short stature and low weight after insufficient catch-up growth in children born SGA. Long-term strategies incorporating GH therapy now remain to be established.     

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.     

Small for gestational age (SGA): endocrine and metabolic consequences and effects of growth hormone treatment

Several studies have demonstrated an association between low birth weight and impaired insulin sensitivity or even type 2 diabetes mellitus (DM2) in later life. Growth hormone (GH) is known to increase fasting and postprandial insulin levels. For that reason concern has been expressed regarding possible detrimental effects of GH therapy in children born SGA. In a Dutch trial the possible side effects of GH therapy on carbohydrate metabolism were assessed in short children born SGA after 6 years and at 6 months after discontinuation of GH therapy. This study included 79 prepubertal short children born SGA, participating in a multicenter double-blind, randomized, dose-response GH trial. Inclusion criteria were: 1) birth length SDS below -1.88, 2) age 3-11 years in boys and 3-9 years in girls, 3) height SDS < -1.88, 4) no spontaneous catch-up growth, and 5) an uncomplicated neonatal period. Mean (SD) value for age was 7.3 (2.1) years, birth length SDS -3.6, height SDS -3.0 (0.7) and BMI SDS -1.2 (1.3). All children were randomly assigned to either group A (n = 41) using 1 mg GH/m2/day or group B (n = 38) using 2 mg/m2/ d/ay (approximately 0.1 or 0.2 IU/kg/d, respectively). Standard oral glucose tolerance tests (OGTTs) were performed before and during 6 years of GH therapy and 6 months after discontinuation of GH therapy. Before GH therapy 8% of the children had impaired glucose tolerance (IGT) according to criteria of the WHO. After 6 years of GH therapy, IGT was found in 4% and after stopping GH in 10%. Mean fasting glucose increased significantly with 0.5 mMol/l after 1 year of GH therapy, without a further increase thereafter. GH therapy induced considerably higher fasting and glucose-stimulated insulin levels. None of the observed changes were different between the GH dosage groups. Children who remained prepubertal had similar glucose and insulin levels compared to children who entered puberty. HbA1c levels were always in the normal range and none of the children developed diabetes mellitus. After discontinuation of GH therapy the mean serum glucose levels remained normal and the mean serum insulin levels decreased significantly, to normal age reference values. Before the start of GH the mean systolic blood pressure was significantly higher compared to age-matched peers, whereas during GH therapy a significant decline in mean systolic blood pressure occurred, which remained similar after discontinuation of GH treatment. In conclusion, continuous, long-term GH therapy in short children born SGA has no adverse effects on glucose levels, even with GH dosages up to 2 mg/m2/day. However, as has been reported in other patient groups, GH induced higher fasting and glucose-stimulated insulin levels, indicating insulin resistance. After discontinuation of GH, serum insulin levels declined to normal age-matched reference levels. Since impaired insulin sensitivity and DM2 have been demonstrated in relatively young patients born SGA, long-term follow-up of children born SGA is advised, also after discontinuation of GH therapy.     

Growth hormone treatment of short children born small for gestational age or with Silver–Russell syndrome: results from KIGS (Kabi International Growth Study), including the first report on final height

The response to growth hormone (GH) therapy was studied in children born small for gestational age (SGA; n = 593) and in those with Silver–Russell syndrome (SRS; n = 127) using data from KIGS (Kabi International Growth Study). For the SGA patients, median birth weight was -2.6 SD scores (SDS), treatment was started at a median age of 9.2 years, at a time when median height was -2.8 SDS while median target height was -1.4 SDS. For the SRS patients, median birth weight was -3.1 SDS, treatment was started at a median age of 7.0 years, at a time when median height was -3.4 SDS with a median target height of -0.1 SDS. GH treatment increased height SDS in both SGA children and patients with SRS; in 16 SGA patients treated to (near) final height with GH (median dose, 0.7 IU/kg/week), height minus target height SDS was -2.0 at the start of treatment and -1.0 at final height. In conclusion, the results obtained in KIGS indicate that GH treatment of short children born SGA is effective in increasing final height above the predicted height and in achieving the target height.     

Efficacy and safety of growth hormone treatment in children born small for gestational age in Japan

Growth-promoting effects and safety of growth hormone (GH) treatment in prepubertal short-statured children born small for gestational age (SGA) were evaluated in a multicenter, open-label, randomized parallel-group comparison study. Patients were randomized to two dose groups; 34 and 33 patients received GH at 0.033 and 0.067 mg/kg/day for one year, respectively. The increase of the mean height velocity standard deviation score (SDS) was significantly (p <0.0001) higher in the 0.067-mg group (from -1.4 to 4.7) than that in the 0.033-mg group (-1.9 to 2.6). A significant (p <0.0001) increase in the mean height SDS was established in the 0.067-mg group; increases of -3.1 to -2.5 vs -3.1 to -2.2 in the 0.033- and 0.067-mg groups, respectively. The trial was non-eventful. Oral glucose tolerance tests indicated a mostly normal pattern of plasma glucose before and after 12-month GH treatment. The growth-promoting effect was significantly higher with GH treatment at 0.067 mg/kg/day.     

Growth in pre-pubertal children with myelomeningocele (MMC) on growth hormone (GH): the KIGS experience

PURPOSE: To analyse the auxological data of children with myelomeningocele (MMC) on growth hormone (GH) therapy whose growth data was documented within KIGS (Pfizer International Growth Database). Longitudinal growth data of a sub-group of pre-pubertal children were studied after a treatment period of 3 years. PATIENTS AND METHODS: Eighty patients (38 m, 42 f) with MMC with a median chronological age (CA) of 11.6 years (at latest visit) on GH were registered in the KIGS database. In 52 patients, GH deficiency was documented. GH therapy started with a median dose of 0.23 mg kg(-1) per week. The 3-year longitudinal growth was analysed in 21 patients (13 m, 8 f; median CA 9.2 years, latest visit), all of whom were pre-pubertal at start and during GH therapy. RESULTS: GH therapy started at 7.5 years with a dose of 0.23 mg kg(-1) per week. Birth length SDS (-0.51) and mid-parental height SDS (+0.07) were in the normal range. BMI SDS at start was +0.24, at latest visit -0.03. After a median treatment duration of 3.0 years (latest visit), height SDS improved from -2.97 (start of GH) to -2.01. The sub-group of pre-pubertal MMC patients started GH therapy (dose 0.22 mg kg(-1) per week) at 6.2 years. Growth velocity (GV) SDS increased significantly (at start: -1.77; 1 year: +2.60, 2 years: +2.25, 3 years: +1.24), thus height SDS improved from -3.25 at start to -1.87 at 36 months. BMI SDS was in the normal range and remained unchanged during GH therapy. No major side effects of GH were recorded. CONCLUSION: GH had positive effects on height SDS in MMC patients. The analysis of the longitudinal growth data of pre-pubertal MMC patients showed a significant increase in GV SDS and improvement of height SDS.     

Intrauterine growth retardation: diagnostic and therapeutic approach

Intrauterine growth retardation (IUGR) refers to the fetal growth pattern and assumes that at least 2 intrauterine growth assessments are performed, indicating a low growth velocity in the fetus. The term "small for gestational age" (SGA) does not refer to fetal growth but to the size of the infant at birth. Infants with SGA have a low weight and/or length for their gestational age at birth below the 10(th) percentile or -2 SD. Approximately 3-5% of all newborns are born SGA. The etiology of SGA/IUGR is not known. The majority (80-85%) of infants born SGA catch-up within the normal range by 2 years of age. SGA has also been associated with increased prevalence of hypertension and dyslipidaemia at a relatively young age. Most controlled trials have shown a beneficial effect of GH treatment. The growth response seems to be due to the cumulative dose received, parenteral adjusted height standard deviation score (SDS) and bone age pretreatment, baseline overnight peak of GH and IGF-I levels. During GH treatment, children born SGA show a significant increase in fasting levels of insulin and proinsulin and a decrease in insulin sensitivity. Fasting glucose levels significantly increase. All these effects are reversible upon interruption of treatment. However, fasting insulin concentrations as well as glucosylated hemoglobin must be carefully monitored during GH treatment. Total cholesterol, LDL cholesterol and the atherogenic index significantly decrease during GH treatment. An acceleration of bone maturation with GH treatment has been reported even though a gain in height SDS for bone age is demonstrated.     

Five years of growth hormone treatment in children with Prader-Willi syndrome. Swedish National Growth Hormone Advisory Group

The authors have followed 18 prepubertal children (3-12 years of age) with Prader-Willi syndrome during 5 years of growth hormone (GH) treatment. Initially, all the children participated in a randomized, controlled GH trial, conducted to assess the effects of GH treatment on growth, body composition and behaviour. GH was administered to group A (n = 9) at a dose of 0.1 IU/kg/day (0.033 mg/kg/day) for 2 years. Group B (n = 9) was untreated for the first year, but the children were given GH at a dose of 0.2 IU/kg/day (0.066 mg/kg/day) during the second year. Thereafter, all children stopped GH treatment for 6 months and were then restarted with GH at a dose of 0.1 IU/kg/day (0.033 mg/kg/day). During the first year of GH treatment, there was a dramatic increase in height SDS in both groups. The attained height percentile was maintained during the continued GH treatment. Five years after the start of GH treatment, mean height SDS is still above average for age. Four children have reached final height, all within 2 SD of target height. During the first year of GH treatment, body mass index (BMI) SDS decreased significantly from 3.0 to 1.5 SDS in group A and from 2.8 to 1.2 SDS in group B, but it increased again during the 6-month period without treatment. Following the restart of GH treatment, BMI SDS has stabilized at 1.7 SDS for group A and 2.5 SDS for group B. In 16 of 18 patients, fasting insulin, glucose and the A1c fraction of glycosylated haemoglobin remained within normal ranges during 5 years of GH treatment. Following a period of rapid weight gain, two children have developed non-insulin-dependent diabetes mellitus. Glucose homeostasis returned to normal when GH treatment was withdrawn. In conclusion, GH treatment has a proven favourable effect on growth and body composition in patients with Prader-Willi syndrome. Treatment should be individualized, and close surveillance of glucose homeostasis is needed, especially if the patient is severely obese.     

The risk of diabetes mellitus in children born small for gestational age and treated with recombinant growth hormone

Children born small for gestational age (SGA) are known to be at risk for both short stature and type 2 diabetes mellitus in later life. To evaluate the influence of recombinant growth hormone (rhGH) therapy on insulin sensitivity, 24 children born SGA were treated with GH at traditional doses, from 0.23 mg/kg/week (group A) to 0.46 mg/kg/week (group B). We evaluated glycosylated haemoglobin, basal glucose and insulin levels before and 1 and 2 years after GH therapy. The homeostasis model assessment (HOMA) index was used to evaluate insulin sensitivity. After 2 years of GH therapy, glycosylated haemoglobin and basal glucose did not change significantly. Insulin sensitivity fell, but still remained within the normal range. In conclusion, 2-year GH therapy had beneficial effects in SGA children without changes in glucose homeostasis. Moreover, the insulin sensitivity reduction did not correlate to the GH dose used.     

Final height in short children born small for gestational age treated with growth hormone

The aim of this observational study was to assess the long-term growth responses to GH treatment of children born small for gestational age (SGA). GH treatment was begun before puberty and continued to final height (FH). Seventy-seven short (height SD score below -2) prepubertal children born SGA (below -2 SD for birth weight and/or birth length), with a broad range of GH secretory capacity, were treated with GH in a daily dose of 33 microg/kg (0.1 U/kg), beginning before the onset of puberty. We observed a difference between adult and pretreatment projected height of 1.3 SD (9 cm) for the entire group. Among the children treated for >2 y before puberty, this mean gain (i.e. difference) in final height was 1.7 SD, whereas the mean gain was 0.9 SD among those in whom treatment was begun <2 y before puberty. Better catch-up growth was observed in the younger (r=-0.56, p<0.0001), shorter (r=-0.49, p<0.0001), and lighter (r=-0.46, p<0.0001) subjects. We conclude that GH treatment improves the final height of short children born SGA. The height gain attained before the onset of puberty is maintained to final height. The younger, shorter, and lighter the child at the start of GH treatment, the better the response. Moreover, most of these SGA individuals treated with GH reach their target height.     

Efficacy and Safety of Up to 8 Years of Long-term Growth Hormone Treatment in Short Children Born Small for Gestational Age in Japan: Analysis of the Subpopulation According to the Japanese Guideline

The efficacy and safety of 8 yr of GH treatment was assessed in 44 Japanese children with small for gestational age (SGA) short stature who met the criteria for GH treatment initiation (height SD score (SDS) <–2.5 SD) of the Japanese guidelines. Height SDS in subjects improved throughout the study period, and average height SDS improved from –3.5 to –1.6 and from –3.4 to –1.9 in the 0.033/0.067 mg and 0.067/0.067 mg groups, respectively, after 8 yr of GH treatment. Delta height SD was approximately +2 after 4 yr of treatment, and ∆ IGF-1 showed a significant positive correlation with ∆ height SD after both 1 and 2 yr (r = 0.415 and 0.488, respectively) of treatment. There was no correlation between the age at the start of treatment and age at onset of puberty, and the median age at the onset of puberty in the subjects was almost the same as that in healthy children. In conclusion, clinically significant improvements in the height SDS was confirmed in short children born SGA after 8 yr of GH treatment without any safety problems.     

Small for gestation and growth hormone therapy

3 to 10% of neonates are born small for gestation (SGA). This usually occurs because of intrauterine growth retardation (IUGR). After birth most SGA infants show good catch-up growth and normalize their height and weight. About 10% of them continue to remain short (<−2SD) and do not achieve normal adult, height, resulting in psychosocial problems. The mechanism of short stature in these children is poorly understood. Infants who do not show catch-up growth usually have an alteration in the GH-IGF-I axis. Diagnostic and management criteria for short stature in SGA were ill-defined in the past. Growth hormone (GH) therapy for improving height in these children has been approved by the FDA. GH therapy leads to growth acceleration and normalization of height during childhood. Long term GH treatment normalizes adult height above-2 SDS in 85% children, and 98% achieve an adult height within their target height range. GH therapy is safe in SGA children, but it is important to monitor for side effects.     

不同剂量重组人生长激素治疗小于胎龄儿矮小症的疗效分析

目的 研究不同剂量重组人生长激素(rhGH)治疗小于胎龄儿(SGA)矮小症的效果和安全性。方法 收集SGA 矮小症患儿37 例,并根据使用剂量分为2 组:小剂量(每日0.1~0.15 IU/kg)rhGH 治疗组和大剂量rhGH 治疗组(每日0.16~0.2 IU/kg),比较两组患儿治疗后3、6、9、12 及24 个月时身高标准差的增长值(ΔHtSDS)、生长速率(HV)、血清胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)水平及空腹血糖等指标的变化。结果 大、小剂量rhGH 治疗后ΔHtSDS 及HV 均有提高,但大剂量组治疗后9、12 及24 个月时ΔHtSDS 及HV 均高于小剂量组(P<0.05)。大剂量和小剂量的rhGH 治疗均使血清IGF-1 和IGFBP-3 水平提高,且血清IGF-1 和IGFBP-3 水平与HtSDS 呈正相关。大小剂量组各有1 例患儿出现一过性空腹血糖轻微升高(均为6.1 mmol/L);两组甲状腺功能均无异常。结论 rhGH 治疗SGA 矮小症效果确切,不良反应少,其中大剂量较小剂量治疗更具优势。     

Gender does not influence prepubertal growth velocity during standard growth hormone therapy--analysis of United States KIGS data

BACKGROUND: Gender is an important determinant that affects the ultimate dose of growth hormone (GH) used for replacement in adult GH deficiency (GHD). Women require larger doses of GH per body weight to achieve comparable age-adjusted serum IGF-I concentrations than do men. OBJECTIVE: To test whether this is entirely a sex steroid effect or biologically inherent in gender. PATIENTS AND METHODS: We examined growth response to GH (0.25-0.35 mg/kg/week) during the first 2 years of therapy in 147 children (44 girls), and in the first 3 years of therapy in 83 of these children (23 girls). Children were aged 3-8 years at onset of therapy, had peak stimulated GH <10 microg/l, and were reported to be prepubertal during the period of analysis. RESULTS: In the relative absence of sex steroid, there was no gender difference in growth velocity SDS or gain in height SDS during 2 or 3 years of GH therapy. CONCLUSIONS: Inherent gender differences in linear growth response to GH prior to puberty may exist, but are not evident in the first years of GH therapy at this GH dose.     

High-dose growth hormone (GH) treatment in prepubertal GH-deficient children

Yokoya S, Araki K, Igarashi Y, Kohno H, Nishi Y, Hasegawa Y, Fujita K, Iwatani N, Tachibana K, Ohyama Y, Seino Y, Satoh M, Fujieda K, Tanaka T. High-dose growth hormone (GH) treatment in prepubertal GH-deficient children. Acta Pædiatr 1999; Suppl 428: 76–9. Stockholm. ISSN 0803–5326
Two clinical studies were conducted to determine the effect of different doses of growth hormone (GH) on prepubertal growth in GH-deficient boys. In one study, GH doses of 1.0 and 1.5 IU/kg/week (0.33 and 0.5 mg/kg/week) were given to groups of five children and compared with a conventional Japanese dose of 0.5 IU/kg/week (0.17 mg/kg/week) in 15 children. A significant dose-dependent increase in height velocity occurred in the first year of treatment, but differences between doses were not significant thereafter. In a second study, GH was administered to ten boys at a dose of 0.5 IU/kg/week for the first year, 0.75 IU/kg/week for the second year, 1.0 IU/kg/week for the third year and 0.5 IU/kg/week for the fourth and subsequent years (0.17, 0.25, 0.33 and 0.17 mg/kg/week, respectively). During the second and third years of GH treatment, these boys had significantly higher growth rates than controls, who were given GH at 0.5 IU/kg/week (0.17 mg/kg/week) throughout, indicating successful reduction in'waning'of the treatment effect. At the end of the fourth year, the different protocols from the two studies had both resulted in a greater height SDS than the controls, and did not advance bone maturation. In conclusion, these protocols may be effective in increasing prepubertal height gain in children with GH deficiency. □ Growth hormone, growth hormone deficiency, high dose     

Growth hormone (GH) treatment to final height in children with idiopathic short stature: evidence for a dose effect

OBJECTIVES: To investigate in an open-label randomized study, the effect of two doses of growth hormone (GH) on final height and height velocity during the first 2 years of treatment of children with idiopathic short stature (mean baseline height standard deviation score [SDS] -3.2). STUDY DESIGN: Patients were treated with GH at 0.24 mg/kg/week, 0.24 mg/kg/week for the first year and at 0.37 mg/kg/week thereafter (0.24-->0.37), or 0.37 mg/kg/week. Final height was evaluated in 50 patients at study completion (mean treatment duration, 6.5 years). RESULTS: Patients who received 0.37 mg/kg/week (n = 72) experienced a significantly greater increase in height velocity than those who received 0.24 mg/kg/week (n = 70) (treatment difference = 0.8 cm/year; P = .003) or 0.24-->0.37 mg/kg/week (n = 67) (treatment difference = 0.9 cm/year; P = .001). For the 50 patients for whom final height measurements were available, mean height SDS increased by 1.55, 1.52, and 1.85 SDS, respectively, for the three dose groups. For the primary comparison between the 0.37 mg/kg/week and 0.24 mg/kg/week dose groups, the mean treatment difference (adjusted for differences in baseline predicted height SDS) was 0.57 SDS (3.6 cm; P = .025). Mean overall height gains (final height minus baseline predicted height) were 7.2 cm and 5.4 cm for the 0.37 mg/kg/week and 0.24 mg/kg/week dose groups, respectively, without dose effects on safety parameters. Final height measurements were within the normal adult height range for 94% of patients randomized to 0.37 mg/kg/week who continued to final height. CONCLUSION: GH treatment dose-dependently increases height velocity and final height in children with idiopathic short stature.     

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.     

Improved final height with long-term growth hormone treatment in Noonan syndrome

Aim: To assess whether children with Noonan syndrome on long-term growth hormone (GH) therapy improve their final height to near mid-parental height. Methods: Twenty-five prepubertal children (13 girls) with Noonan syndrome (NS) were studied. A single clinician made the diagnosis based on clinical criteria. GH treatment started at an age ranging from 3.1 to 13.8 y and was continued for at least 2 y. Improvement or “gain” in final height (FH) was defined as either the difference between adult height SD scores (SDS) and pre-treatment height SDS (the childhood component of the Swedish reference) or height SDS compared to the Noonan reference. Results: Ten children received a GH dose of 33 μg/kg/d (mean age at start 7.7±2.1 y, mean age at stop 17.6±1.7 y) and 15 received a dose of 66 μg/kg/d (mean age at start 8.6±3.3 y, mean age at stop 18.4±2.1 y). Eighteen out of 25 patients reached FH. A substantial improvement in FH of 1.7 SDS, equivalent to 10.4 cm compared to pre-treatment height, was observed. No significant difference was seen between the two GH doses. Females gained a mean height of 9.8 cm and males 1-13 cm (FH 174.5±7.8 cm vs mean adult height of 162.5±5.4 cm for males with NS) at final height. Moreover, 60% reached a mid-parental height of±1 SD.

Conclusion: GH treatment improves final height in patients with Noonan syndrome, with a mean gain of 1.7 SDS. The prepubertal height gain is maintained to final height and the children achieve a height close to their mid-parental height.     

Effect of growth hormone (GH) during puberty in GH-deficient children: preliminary results from an ongoing randomized trial with different dose regimens

This paper reports results from an ongoing, randomized, multicentre national trial. The aim is to elucidate whether a dose of growth hormone (GH) of 0.2 IU/kg (0.07 mg/kg), given either as once-daily or twice-daily injections during puberty, is more effective than a once-daily dose of 0.1 IU/kg/day (0.03 mg/kg/day) in improving final height in children with GH deficiency (GHD). The twice-daily regimen comes closer to the spontaneous GH secretion pattern in puberty. Ninety-two children with GHD who had been receiving GH therapy for at least 1 year, and with spontaneous puberty or who were prepubertal and due to be started on replacement therapy to induce puberty, were randomly assigned to receive GH as follows: group A, 0.1 IU/kg/day (0.03 mg/kg/day), administered once daily; group B, 0.2 IU/kg/day (0.07 mg/kg/day), administered once daily; and group C, 0.2 IU/kg/day (0.07 mg/kg/day), divided into two equal injections given at 12-hour intervals. Pubertal height gain was 0.7, 0.7 and 1.3 SDS for groups A, B and C, respectively. The gain in height during puberty was thus most marked in group C. Mean final height, when corrected for parental height, was between 0 and 1 SDS in all treatment groups. All but seven children reached a final height within +/- 2 SD of the general population. There was a wide range of final heights in all three treatment groups. This variation in response suggests the need to individualize treatment in order to achieve an appropriate final height for most individuals.     

Effect of growth hormone (GH) during puberty in GH-deficient children: preliminary results from an ongoing randomized trial with different dose regimens

Albertsson Wikland K, Alm F, Aronsson S, Gustafsson J, Hagenas L, Hager A, Ivarsson S, Kristrom B, Marcus C, Moe11 C, Nilsson KO, RitzCn M, Tuvemo T, Westgren U, Westphal 0, Aman J. Effect of growth hormone (GH) during puberty in GH-deficient children: preliminary results from an ongoing randomized trial with different dose regimens. Acta Pxdiatr 1999; Suppl 428:80-4. Stockholm. ISSN 0803-5326
This paper reports results from an ongoing, randomized, multicentre national trial. The aim is to elucidate whether a dose of growth hormone (GH) of 0.2 IUkg (0.07 mgkg), given either as once-daily or twice-daily injections during puberty, is more effective than a once-daily dose of 0.1 IU/kg/day (0.03 mg/kg/day) in improving final height in children with GH deficiency (GHD). The twice-daily regimen comes closer to the spontaneous GH secretion pattern in puberty. Ninety-two children with GHD who had been receiving GH therapy for at least 1 year, and with spontaneous puberty or who were prepubertal and due to be started on replacement therapy to induce puberty, were randomly assigned to receive GH as follows: group A, 0.1 IU/kg/day (0.03 mg/kg/day), administered once daily; group B, 0.2 IU/kg/day (0.07 mg/kg/day), administered once daily; and group C, 0.2 IUkg/day (0.07 mg/kg/day), divided into two equal injections given at 12-hour intervals. Pubertal height gain was 0.7, 0.7 and 1.3 SDS for groups A, B and C, respectively. The gain in height during puberty was thus most marked in group C. Mean final height, when corrected for parental height, was between 0 and 1 SDS in all treatment groups. All but seven children reached a final height within 2 SD of the general population. There was a wide range of final heights in all three treatment groups. This variation in response suggests the need to individualize treatment in order to achieve an appropriate final height for most individuals. □ Dose, final height, growth hormone treatment, puberty, randomized treatment trial