Effect of growth hormone on height,weight, and body composition in Prader-Willi syndrome

AIMS—To evaluate the effect of the administration of growth hormone on stature, body weight, and body composition in children aged between 4 and 10 years with Prader-Willi syndrome.
METHODS—Height, weight, and skinfold thickness were recorded in 25 children using standard anthropometric techniques at recruitment, and six months later, shortly before the start of daily subcutaneous injections of growth hormone. Body composition was assessed via a measurement of total body water using stable isotopes. Measurements were repeated at the end of the six months of growth hormone administration. Measurements of height, weight, and skinfold thickness were expressed as standard deviation scores (SDSs).
RESULTS—There was a significant reduction in the percentage of body fat after growth hormone treatment; height velocity doubled during treatment; body weight did not change significantly when expressed as an SDS. Skinfold thickness at both the triceps and subscapular site decreased in absolute terms and when expressed as an SDS.
CONCLUSIONS—These results indicate sufficient potential benefit to justify a more prolonged trial of growth hormone treatment and an exploration of different dosage regimens in children with Prader-Willi syndrome.

     

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.     

Predictors of first-year growth response to a fixed-dose growth hormone treatment in children born small for gestational age: results of an open-label, multicenter trial in the United States

BACKGROUND: Previous studies of varied populations of non-uniformly defined children born small for gestational age (SGA) receiving different growth hormone (GH) regimens have found that GH treatment increased growth velocity and adult height and was safe. The GH dose was the major predictor of first year growth response. AIM: To identify pre- and within-treatment predictors of growth in well defined children born SGA treated with a fixed dose of GH. METHODS: 139 short, prepubertal children born SGA (i.e. birth weight and/or length > or =2 standard deviations below the mean) received Genotropin (rhGH) at 0.24 mg/kg/wk for 1 month then an additional 11 months at a dose of 0.48 mg/kg/wk, the FDA-approved dose of GH for children born SGA. RESULTS: Height improved significantly by month 3, with progressive improvement over the entire 12 months (median height SDS change of 0.78). Pretreatment predictors of growth included baseline bone age, IGFBP-3, total cholesterol, WBC and height SDS minus mid-parental height SDS. Within-treatment predictors of the change (Delta) height SDS at month 12 were the A height SDS at months 3 and 6 and growth velocity SDS at months 3 and 6. CONCLUSION: GH at 0.48 mg/kg/wk was well tolerated and improved growth in children born SGA; the Delta IGF-I was not predictive of the 12 month height SDS gain, while the Delta height SDS at 3 and 6 months were predictive. Underweight children grew as well as normal weight children, and both groups showed improved body composition following GH treatment.     

Metabolic effects of growth hormone treatment: an early predictor of growth response?

Fourteen children receiving one year of recombinant human growth hormone (rhGH) treatment underwent measurement of serial changes in body composition (measured by skinfold thickness, bioelectrical impedance, and H2(18)O dilution), resting energy expenditure (REE, estimated by ventilated hood indirect calorimetry), and total free living daily energy expenditure (TEE, measured by the doubly labelled water technique). Mean height velocity increased from 4.9 to 8.6 cm/year after six months of treatment. Fat free mass (FFM) increased more during the first six weeks (24.4 g/day) than from six to 26 weeks of treatment (6.8 g/day); fat mass decreased by 7.2 g/day and 1.1 g/day respectively. The six week increase in REE (kJ/day) was maintained after six months of treatment, though expressed per kilogram FFM (kJ/kgFFM/day), returned to pretreatment values by three months. Height velocity increases at six months correlated with six week changes in fat mass measured by skinfold thickness and REE, though use of this relationship to predict growth response in individuals is limited by the wide 95% prediction intervals. No significant changes in growth, body composition, or energy expenditure were observed between six and 12 months of treatment, in either patients who had initially responded well to treatment or those who were poor initial responders to treatment and who had their dose of rhGH doubled after six months.     

Metabolic effects of growth hormone treatment: an early predictor of growth response?

Fourteen children receiving one year of recombinant human growth hormone (rhGH) treatment underwent measurement of serial changes in body composition (measured by skinfold thickness, bioelectrical impedance, and H2(18)O dilution), resting energy expenditure (REE, estimated by ventilated hood indirect calorimetry), and total free living daily energy expenditure (TEE, measured by the doubly labelled water technique). Mean height velocity increased from 4.9 to 8.6 cm/year after six months of treatment. Fat free mass (FFM) increased more during the first six weeks (24.4 g/day) than from six to 26 weeks of treatment (6.8 g/day); fat mass decreased by 7.2 g/day and 1.1 g/day respectively. The six week increase in REE (kJ/day) was maintained after six months of treatment, though expressed per kilogram FFM (kJ/kgFFM/day), returned to pretreatment values by three months. Height velocity increases at six months correlated with six week changes in fat mass measured by skinfold thickness and REE, though use of this relationship to predict growth response in individuals is limited by the wide 95% prediction intervals. No significant changes in growth, body composition, or energy expenditure were observed between six and 12 months of treatment, in either patients who had initially responded well to treatment or those who were poor initial responders to treatment and who had their dose of rhGH doubled after six months.     

Insulin-like growth factor I, IGF binding protein 3, and IGFBP protease activity: relation to anthropometric indices in solid tumours or leukaemia.

OBJECTIVES: To measure the serum concentrations of insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3), and the level of IGFBP-3 protease activity in 38 children presenting with malignancies, and to assess their relation with auxological parameters and nutritional status. METHODS: Height, weight, skinfold thickness, and mid-upper arm circumference (MUAC) were recorded using standard techniques. IGF-I and IGFBP-3 were measured using specific radioimmunoassays. Serum IGFBPs were also visualised on western ligand blot. IGFBP-3 protease activity was assessed by the extent of fragmentation of recombinant [125I]-IGFBP-3, compared with that induced by pregnancy serum. Anthropometric and radioimmunoassay data were expressed as standard deviation scores (SDS). RESULTS: The median (range) IGF-I SDS was significantly reduced in all patients (-1.1 (-5.1 to 1.2)) and lower in children who were malnourished (-2.5 (-3.9 to 0.1)). IGFBP-3 SDS was within the normal range for 31 of 38 patients but IGFBP-3 protease activity was raised in all patients. Neither IGFBP-3 concentration nor protease activity was affected by nutritional status. IGF-I correlated with MUAC (r = 0.41) and subscapular skinfold thickness SDS (r = 0.38), but not with weight, height, weight for height, or triceps skinfold thickness. CONCLUSIONS: IGF-I is low in children with malignancies, and even lower in those who are malnourished. IGFBP-3 concentrations were normal in most patients but interpretation is complicated by the presence of raised IGFBP-3 protease activity, which could lead to overestimating concentrations of intact peptide. IGF-I appears to relate to arm anthropometry as an index of nutritional status but not height, weight, or weight for height, as would be expected in normal children.     

Growth hormone treatment of children with Prader-Willi syndrome affects linear growth and body composition favourably

We have compared the growth and the body composition in children with Prader-Willi syndrome (PWS) with and without growth hormone treatment (recombinant GH 0.1 IU/kg/day) after a 1-y period. Twenty-nine prepubertal children with PWS, with mean body mass index (BMI) SDS of 2.2, and 10 (control) healthy obese children with mean BMI SDS of 5.6, underwent 24-h frequent blood sampling. Both PWS and control obese children had low and similar GH levels (0.7 /ng/l ± 0.4 SD). Serum IGF-I levels, however, were significantly lower in children with PWS (-1.5 SDS ± 0.8 SD vs -0.2 SDS ±0.8 SD). The 29 PWS children were randomized into 2 groups of 15 and 14 subjects for GH treatment and no treatment, respectively. Height velocity increased from -1.9 SDS to + 6.0 SDS in the treated group ( p < 0:001) and decreased from -0.1 SDS to -1.4 SDS in the control PWS group during the study year. BMI decreased significantly for the treated group (+3.0 SDS to + 2.0 SDS). Relative fat mass decreased significantly, while fat-free mass increased ( p < 0:001) for the treated group. No significant changes were noticed in body composition in the control PWS group. In conclusion, the low spontaneous 24-h GH secretion, regardless of body weight, and the exceptional response to growth hormone treatment together with the finding of low IGF-I levels suggest that growth hormone deficiency is a common feature of PWS, as a result of hypothalamic dysfunction. Treatment with growth hormone is beneficial for the majority of PWS children.     

Physical effects of growth hormone treatment in children with Prader-Willi syndrome

A randomized, controlled study of 54 children (age, 4-16 years) with Prader-Willi syndrome was conducted to assess the potential beneficial effects of growth hormone (GH) treatment. After observation for 6 months, the children were randomized to receive GH at a dose of 3 IU/m2/day (1 mg/m2/day) (n = 35) or no intervention (n = 19). The effects of GH treatment on linear growth, body composition, muscle strength, pulmonary function and resting energy expenditure were assessed. The levels of GH secreted in response to clonidine stimulation were universally low, and mean (+/- SD) insulin-like growth factor I SDS was -1.2 +/- 0.8 pretreatment. In children treated for 1 year, mean height velocity SDS significantly increased from -1.0 +/- 2.5 to 4.6 +/- 2.9 (p < 0.0001), mean percentage body fat decreased from 46.3 +/- 8.4% to 38.4 +/- 10.7% (p < 0.001), mean lean body mass increased from 20.5 +/- 6.3 kg to 25.6 +/- 4.3 kg (p < 0.01) and respiratory muscle function and physical strength improved. Mean respiratory quotients significantly decreased from 0.81 to 0.77 (p < 0.001); however, resting energy expenditure did not change. Therefore, GH therapy appears to reduce some of the physical disabilities experienced by children with Prader-Willi syndrome.     

Physical effects of growth hormone treatment in children with Prader-Willi syndrome

A randomized, controlled study of 54 children (age, 4-16 years) with Prader-Willi syndrome was conducted to assess the potential beneficial effects of growth hormone (GH) treatment. After observation for 6 months, the children were randomized to receive GH at a dose of 3 IU/m²/day (1 mg/m²/day) ( n = 35) or no intervention ( n = 19). The effects of GH treatment on linear growth, body composition, muscle strength, pulmonary function and resting energy expenditure were assessed. The levels of GH secreted in resonse to clonidine stimulation were universally low, and mean (± SD) insulin-like growth factor I SDS was -1.2 ± 0.8 pretreatment. In children treated for 1 year, mean height velocity SDS significantly increased from -1.0 ± 2.5 to 4.6 ± 2.9 ( p < 0.0001), mean percentage body fat decreased from 46.3 ± 8.4% to 38.4 ± 10.7% ( p < 0.001), mean lean body mass increased from 20.5 ± 6.3 kg to 25.6 ± 4.3 kg ( p <0.01) and respiratory muscle function and physical strength imporved. Mean respiratory quotients significantly decreased from 0.81 to 0.77 ( p < 0.001); however, resting energy expenditure did not change. Therefore, GH therapy appears to reduce some of the physical disabilities experienced by children with Prader-Willi syndrome.     

Insulin-like growth factor I,IGF binding protein 3, and IGFBP protease activity: relation to anthropometric indices in solid tumours or leukaemia

OBJECTIVES—To measure the serum concentrations of insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3), and the level of IGFBP-3 protease activity in 38 children presenting with malignancies, and to assess their relation with auxological parameters and nutritional status.METHODS—Height, weight, skinfold thickness, and mid-upper arm circumference (MUAC) were recorded using standard techniques. IGF-I and IGFBP-3 were measured using specific radioimmunoassays. Serum IGFBPs were also visualised on western ligand blot. IGFBP-3 protease activity was assessed by the extent of fragmentation of recombinant [¹²⁵I]-IGFBP-3, compared with that induced by pregnancy serum. Anthropometric and radioimmunoassay data were expressed as standard deviation scores (SDS).RESULTS—The median (range) IGF-I SDS was significantly reduced in all patients (?1.1 (?5.1 to 1.2)) and lower in children who were malnourished (?2.5 (?3.9 to 0.1)). IGFBP-3 SDS was within the normal range for 31 of 38 patients but IGFBP-3 protease activity was raised in all patients. Neither IGFBP-3 concentration nor protease activity was affected by nutritional status. IGF-I correlated with MUAC (r = 0.41) and subscapular skinfold thickness SDS (r = 0.38), but not with weight, height, weight for height, or triceps skinfold thickness.CONCLUSIONS—IGF-I is low in children with malignancies, and even lower in those who are malnourished. IGFBP-3 concentrations were normal in most patients but interpretation is complicated by the presence of raised IGFBP-3 protease activity, which could lead to overestimating concentrations of intact peptide. IGF-I appears to relate to arm anthropometry as an index of nutritional status but not height, weight, or weight for height, as would be expected in normal children.     

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.     

Effects of 5 years growth hormone treatment in patients with Prader-Willi syndrome

BACKGROUND: Short-term studies showed favorable effects of growth hormone (GH) treatment in patients with Prader-Willi syndrome (PWS). AIMS: To evaluate the long-term effects of GH therapy in patients with PWS retrospectively. PATIENTS AND METHODS: Effects of GH treatment (0.5 IU/kg/w s.c.) for a period of 1 to 5 years were assessed for 37 Japanese patients with PWS aged 3-(9/12) to 21-(3/12) years. Height and weight were expressed as standard deviation scores (SDSs) of Japanese PWS patients. Height velocity, final height, body mass index (BMI) and Rohrer index were also evaluated. RESULTS: After 1 year of treatment, the mean height velocity improved significantly from 4.32 to 8.69 cm per year (p < 00001). After 5 years of treatment, mean height SDS increased from -0.99 to +0.88 (p = 0.003). Mean final height of treated patients was 158.0 cm in males and 147.7 cm in females. Mean Rohrer index improved from 182 to 164 (p < 0.0001) after 1 year of treatment and stayed stable thereafter. CONCLUSIONS: Long-term treatment with GH in patients with PWS improved height velocity, height SDS, final height, and the degree of obesity. These data encourage the long-term use of GH in these patients.     

Sustained benefits of growth hormone on body composition, fat utilization, physical strength and agility, and growth in Prader-Willi syndrome are dose-dependent

BACKGROUND: Obesity and hypotonia in children with Prader-Willi syndrome (PWS) are accompanied by abnormal body composition resembling a growth hormone (GH) deficient state. Hypothalamic dysfunction in PWS includes decreased GH secretion, suggesting a possible therapeutic role for GH treatment. While recent studies have demonstrated short-term benefits of treatment with GH, a critical question is whether beneficial changes persist or wane with prolonged therapy, and whether these effects on body composition are dose-dependent as seen in adult GH deficiency. OBJECTIVES AND METHODS: After 24 months of GH theapy at a dose of 1 mg/m2/day ("standard dose"), the effects of 12 additional months of GH treatment at varying doses (0.3-1.5 mg/m2/day) on growth, body composition, strength and agility, pulmonary function, resting energy expenditure (REE), and fat utilization were assessed in 46 children with PWS. Percent body fat, lean muscle mass, and bone mineral density (BMD) were measured by dual X-ray absorptiometry (DXA). Indirect calorimetry was used to determine REE and to calculate respiratory quotient (RQ). RESULTS: During months 24-36 of GH therapy, further changes in body composition (decrease in fat mass, and increase in lean body mass), growth velocity, and REE occurred with standard and higher-dose GH therapy (1.5 mg/m2/day), but not with lower dose GH (0.3 mg/m2/day). Prior improvements in BMD, and strength and agility, which occurred during the initial 24 months, were sustained during the additional 12 months (to 36 months) regardless of dose. CONCLUSIONS: Salutary and sustained GH-induced changes in growth, body composition, and physical function in children with PWS require GH doses of >0.3 mg/m2/day. Conversely, BMD increased during the additional 12 months of therapy regardless of GH dose. Lower doses of GH, effective in improving body composition in adults with GHD, do not appear to be effective in children with PWS.     

Standards for selected anthropometric measurements in Prader-Willi syndrome

We report standards (95th, 50th, and 5th centiles) in Prader-Willi syndrome for weight, height, sitting height, head circumference, head length, head breadth, hand length, middle finger length, palm length, hand breadth, foot length, foot breadth, triceps skinfold, and subscapular skinfold. For comparison with Prader-Willi syndrome standardized curves, normal control data from the literature were plotted similarly and standard curves were produced. We encourage the use of these standards with the examination of patients who have Prader-Willi syndrome and in the comparison of the patient who has Prader-Willi syndrome with other similarly affected individuals. The standards may also be useful for assisting in the diagnosis of Prader-Willi syndrome, particularly in younger individuals.     

The effect of human growth hormone therapy on skinfold thickness in growth hormone-deficient children

Skinfold thickness (ST) was measured in 43 children with various forms of growth hormone (GH) deficiency during the first year of GH therapy. The average (and SEM) initial ST, expressed as standard deviation score (SDS) was 1.17 (0.25) for subscapular, 0.63 (0.18) for triceps, and 0.40 (0.21) for biceps ST. During therapy the average decrease is 1 SD. Children in the pubertal age group and those with partial GH deficiency showed smaller decreases. A larger decrease of triceps ST was associated with lower GH and insulin peaks, and lower age, bone age and initial weight-for-height. Some correlations between ST decrease and growth response in the first year were significant, but still too low to allow of reliable predictions. The same was true for other clinical parameters. These data indicate that a chronic lack of GH leads to unequal fat distribution, possibly due to different sensitivities to GH in the trunk and extremities. The variability of ST responses to GH therapy limits clinical applications.Abbreviations GH growth hormone - hGH human growth hormone - SDS standard deviation score - SDS_BA standard deviation score for bone age - SDS_CA standard deviation score for chronological age - SEM standard error of the mean - ST skin fold thickness - ST-SDS skinfold thickness, expressed as a standard deviation score - ST-log skinfold thickness, expressed as 100.log₁₀ (reading in 0.1 mm-18) - TSH thyroid stimulating hormone     

The obesity hypoventilation syndrome and the Prader-Willi syndrome

Fourteen children with the Prader-Willi syndrome have been managed at the Royal Alexandra Hospital for Children between the years 1964-1980--twelve male, two female. Six male children developed features of the obesity hypoventilation syndrome. The age of onset of this complication ranged from 4.0 to 12.6 years. With one exception those children with the obesity hypoventilation syndrome were more obese than those without it. At the time of onset of the syndrome, five of six patients had weights greater than or equal to 6.5 standard deviations above ideal body weight. Those children without the obesity hypoventilation syndrome had a range of standard deviations 1.0 to 4.2 above the ideal body weight. In four of six cases weight reduction and a cardiac failure regimen resulted in reversal of the obesity hypoventilation syndrome. With two of the six children there had been cardiomegaly and increased pulmonary venous vascularity on x-ray at a chronological age of three months. Two of the six children died.     

Sustained benefit after 2 years of growth hormone on body composition, fat utilization, physical strength and agility, and growth in Prader-Willi syndrome

BACKGROUND: Obesity and hypotonia in children with Prader-Willi syndrome (PWS) are accompanied by abnormal body composition resembling a growth hormone (GH)-deficient state. Hypothalamic dysfunction in PWS includes decreased GH secretion, suggesting a possible therapeutic role for GH treatment. Although recent studies have demonstrated short-term benefits of treatment with GH, a critical question is whether beneficial changes persist or wane with prolonged therapy. OBJECTIVES AND METHODS: Effects of 24 months of GH treatment (1 mg/m(2)/d) on growth, body composition, strength and agility, pulmonary function, resting energy expenditure, and fat utilization were assessed in 35 children with PWS. Percent body fat, lean muscle mass, and bone mineral density were measured by dual-energy x-ray absorptiometry. Indirect calorimetry was used to determine resting energy expenditure and to calculate the respiratory quotient. RESULTS: Compared with baseline evaluations, increased height velocity (SD score -1.1 +/- 2.5 to 2.2 +/- 2.3; P <. 001), reduced percent body fat (46.4% +/- 8.4% to 40.3% +/- 10.0%, P <.001), and improved respiratory muscle function and physical strength and agility (sit-ups, weight-lifts, running speed, and broad jump; P <.01) were observed after 24 months of GH treatment. A decline in respiratory quotient (0.81 +/- 0.07 to 0.75 +/- 0.06; P <. 01) and a trend toward increased resting energy expenditure were also observed. Changes in response to GH occurred predominantly during the initial 12 months of GH therapy. CONCLUSIONS: Children with PWS had sustained increases in lean body mass, decreases in percent body fat, improvements in physical strength and agility, and increased fat oxidation after 24 months of GH therapy. However, between 12 and 24 months, the growth rate slowed. Consequently, encouraging initial results require even more prolonged study to draw conclusions regarding the long-term value of GH therapy in changing body composition in children with PWS.     

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     

Growth hormone treatment of patients with Prader-Willi syndrome. Swedish Growth Hormone Advisory Group

Several studies have now been published on the effect of one or several years of growth hormone treatment on growth and body composition of children with Prader-Willi syndrome. The majority of the patients have responded with greatly increased growth rate, decreased body fat and increased muscle volume. Many of these children seem to have a functional growth hormone deficiency, probably secondary to their hypothalamic dysfunction. Further studies are needed to establish the long-term effect of this treatment on somatic and psychological well-being.     

Growth hormone and body composition in children younger than 2 years with Prader-Willi syndrome

OBJECTIVES: To assess body composition of infants with Prader-Willi syndrome (PWS) by using deuterium dilution and investigating the efficacy of early institution of growth hormone (GH) therapy in increasing lean mass (LM) and preventing massive obesity. STUDY DESIGN: One group of 11 children with PWS <2 years before and during 30-month GH therapy (GH group) was compared with 6 infants administered only coenzyme Q(10) for 1 year (Q10 group). LM adjusted for height (LM(Ht)) and relative fat mass (%FM(Age)) standard deviation scores (SDS) were calculated from data of 95 healthy children. RESULTS: Initially, LM(Ht) of all patients was below the normal average. LM(Ht) decreased by -0.46 +/- 0.3 SD (P=.03) per year in the Q10 group but rose by 0.25 +/- 0.3 SD (P=.02) per year during GH therapy, normalizing after 30 months (-0.70 +/- 1.0 SD). Despite low to normal weight for height (WfH), %FM(Age) was above the normal average (GH group, 31.0% +/- 4.5%, Q10 group, 32.4% +/- 9.5%). In the Q10 infants, %FM(Age) increased by 0.71 +/- 0.7 SD per year, whereas in the GH group, %FM(Age) remained more stable up to 30 months. CONCLUSIONS: Diminished LM(Ht) found in infants with PWS further declines during the early years. Early institution of GH therapy lifts LM(Ht) into the normal range and delays fat tissue accumulation.