Year Of rhGH Therapy Research Articles

Growth hormone and the risk of atherosclerosis in growth hormone-deficient children

ObjectiveGrowth hormone-deficient (GHD) children have been found to have higher cardiovascular mortality rates and an increased carotid intima-media thickness (CIMT). This study investigated the risk of atherosclerosis and the effect of recombinant growth hormone (rhGH) replacement therapy on the lipid profile and CIMT in GHD children. DesignA total of 40 GHD children (mean age: 12.3±2.04years) were investigated before and after 1year of rhGH therapy at a dosage of 0.03mg/kg/day and 40 age- and sex-matched healthy children (mean age: 12.1±2.23years) were enrolled as a control group, in the same pubertal stage. Fasting blood samples were obtained for lipid profile, IGF-1, and IGFBP-3 analyses. The patients and controls underwent CIMT measurements before and after 1year of rhGH treatment. ResultsThe growth velocity and height standard deviation scores increased significantly over 1year of treatment in all patients. The total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and atherogenic index (Ai) values were increased while the high-density lipoprotein (HDL) cholesterol value was decreased in the GHD children, as compared to the controls; however, the triglyceride (TG) level was comparable. After 1year of treatment, a significant decrease in the TC, LDL cholesterol, and Ai values as well as a significant increase in the HDL value were observed in the GHD patients, with the values becoming similar to those in the control group. The mean CIMT was significantly greater in the GHD subjects than in the controls. After 1year of therapy, the CIMT in the GHD subjects had decreased significantly; however, it was still greater than that in the control group. IGF-1 was negatively correlated with TC, LDL cholesterol, Ai, right CIMT, and left CIMT. ConclusionsGHD is associated with increased atherosclerotic risk in children. An improved lipid profile and CIMT were detected after 1year of hormone replacement therapy.

Stimulant Use and Its Impact on Growth in Children Receiving Growth Hormone Therapy: An Analysis of the KIGS® International Growth Database

Background: Children receiving stimulants for attention deficit hyperactivity disorder (ADHD) frequently present to pediatric endocrinology clinics for evaluation and treatment of growth disorders. The worldwide prevalence of stimulant use in children with ADHD also receiving recombinant human growth hormone (rhGH) and the impact on response to rhGH are unknown. Methods: Data on children enrolled in the KIGS® (Pfizer International Growth Study) registry were evaluated for the associated diagnosis of ADHD prior to initiation of Genotropin® rhGH. Concomitant stimulant medications and auxological information were captured. Response to rhGH was evaluated using established growth prediction models. Results: The prevalence of ADHD in KIGS was 2.3% (1,748/75,251), with stimulants used in 1.8% (1,326/75,251). Children with idiopathic growth hormone deficiency (IGHD) who received stimulants grew significantly less (1.1 cm) in the first year of rhGH therapy than expected for rhGH-treated non-ADHD IGHD children. After one year of rhGH, idiopathic short stature (ISS) children with ADHD were significantly shorter [0.74 cm (with stimulants) and 0.69 cm (without stimulants)] than non-ADHD ISS children. Conclusions: We demonstrated an impaired response to rhGH in IGHD and ISS children with ADHD. Our findings suggest that the ADHD phenotype, alone or in conjunction with stimulant therapy, may impair the short-term growth response to rhGH.

Effect of one-year growth hormone therapy on body composition and cardio-metabolic risk in Indian children with growth hormone deficiency

Growth hormone (GH) deficiency in children manifests as short stature but is also associated with metabolic disturbances. Paucity of GH is also likely to be associated with increased intima media thickness. Data on body composition (BC) and carotid intima media thickness (cIMT) in children with growth hormone deficiency (GHD) from developing countries are very scarce. Therefore, objectives of present study were to assess effect of 1 year of rhGH therapy on (i) BC and lipid profile (LP) in a cohort of Indian GHD children and (ii) effect on atherosclerotic markers – cIMT in subsample. Anthropometry, BC [% body fat (BF), % lean body mass (LBM), bone mineral content (BMC)] (DXA) and LP were measured in 49 pre-pubertal GHD-children (9.3 ± 3.1 years) at baseline and after 1 year of rhGH therapy. On subset of 20 children, cIMT of right common carotid artery was also measured. Baseline BC parameters were compared with age-gender matched healthy controls (n = 49). At baseline % BF was 23 ± 9 %, LBM was 9 ± 3 kg and BMC was 0.306 ± 0.15 kg in GHD- children; BF was comparable, while lean and bone were less than controls (p < 0.05). Post therapy, significant reduction in fat (15%), and cIMT (7%) and increase in LBM and BMC by 40% and 44%, respectively (p < 0.05) was seen. Our cohort of untreated GHD children had abnormal BC and cIMT as compared to controls. rhGH therapy for 1 year had beneficial effect on BC and cardiovascular risk factors.

Effects of Recombinant Human Growth Hormone for 1 Year on Body Composition and Muscle Strength in Children on Long-Term Steroid Therapy: Randomized Controlled, Delayed-Start Study

Recombinant human GH (rhGH) improves growth and body composition in glucocorticoid-treated children. Its effects on muscle strength are poorly evaluated. Our objective was to evaluate rhGH effects on muscle strength in children receiving long-term glucocorticoid therapy; effects on height SD score (SDS) and body composition were assessed also. A randomized, controlled, delayed-start study of rhGH for 12 months was started after randomization (baseline) or 6 months later (M6). Patients included 30 children with various diagnoses. rhGH was administered at 0.065 mg/kg/d for 6 months and then in the dosage maintaining serum IGF-I levels below +2 SDS for chronological age. The primary criterion was the between-group difference in composite index of muscle strength (CIMS) change at M6. Secondary criteria included between-group differences in CIMS SDS(height), lean mass (LM), thigh muscle area (MA), and height SDS changes at M6; these parameters were also assessed in the overall population after 1 year of rhGH therapy. At M6, rhGH therapy did not significantly affect changes in CIMS or CIMS SDS(height) (+17.6% vs +7.5% and +0.14 ± 0.38 vs +0.11 ± 0.62, respectively); the rhGH-treated group had significantly larger changes in height SDS (+0.2 [0.3] vs -0.2 [0.3]; P = 0.003), LM (+7.3% [+3.7%; +21.6%] vs 0% [-4.7%; +3.2%]; P = 0.002), and MA (+8.8% [+5%; +15.6%] vs. -0.6% [-6.3%; +7.7%]; P = 0.01) compared with the untreated group. After 1 year of rhGH, height SDS, LM, and MA increased significantly, CIMS increased by 24.7% (+5.8%; +34.2%), and CIMS SDS(height) remained within the normal range. rhGH increased height, LM, and MA. However, muscle strength did not improve significantly.

The Interactive Effect ofGHR-Exon 3and −202 A/C IGFBP3Polymorphisms on rhGH Responsiveness and Treatment Outcomes in Patients with Turner Syndrome

There is great interindividual variability in the response to recombinant human (rh) GH therapy in patients with Turner syndrome (TS). Ascertaining genetic factors can improve the accuracy of growth response predictions. The objective of the study was to assess the individual and combined influence of GHR-exon 3 and -202 A/C IGFBP3 polymorphisms on the short- and long-term outcomes of rhGH therapy in patients with TS. GHR-exon 3 and -202 A/C IGFBP3 genotyping (rs2854744) was correlated with height data of 112 patients with TS who remained prepubertal during the first year of rhGH therapy and 65 patients who reached adult height after 5 ± 2.5 yr of rhGH treatment. First-year growth velocity and adult height were measured. Patients carrying at least one GHR-d3 or -202 A-IGFBP3 allele presented higher mean first-year growth velocity and achieved taller adult heights than those homozygous for GHR-fl or -202 C-IGFBP3 alleles, respectively. The combined analysis of GHR-exon 3 and -202 A/C IGFBP3 genotypes showed a clear nonadditive epistatic influence on adult height of patients with TS treated with rhGH (GHR-exon 3 alone, R² = 0.27; -202 A/C IGFBP3, R² = 0.24; the combined genotypes, R² = 0.37 at multiple linear regression). Together with clinical factors, these genotypes accounted for 61% of the variability in adult height of patients with TS after rhGH therapy. Homozygosity for the GHR-exon3 full-length allele and/or the -202C-IGFBP3 allele are associated with less favorable short- and long-term growth outcomes after rhGH treatment in patients with TS.

Results of recombinant growth hormone treatment in children with end-stage renal disease on regular hemodialysis

Children with chronic kidney disease are at high risk for growth retardation and decreased adult height. Growth hormone (GH) treatment is known to stimulate growth in children with short stature suffering from chronic kidney disease. However, the extent to which this therapy affects final adult height is not known. This study was performed on 15 patients with end-stage renal disease (ESRD) on regular hemodialysis to detect the effect of using recombinant human growth hormone (rhGH) on growth of patients with ESRD on regular hemodialysis and comparing this effect with the growth velocity in the same group without using rhGH in the year before therapy. There were eight females and seven males with mean age 10.6 ± 2.8 (range 5-14 years). For each patient, recombinant GH was given for one year, three-times weekly. The data of these 15 patients was compared with the year before treatment versus data of the same group of patients after six months and after one year of rhGH therapy. Our results showed that, in the year before therapy, height of these patients increased from a mean of 112.1 ± 11.6 cm to 112.7 ± 11.5 cm, which is a non-significant increase statistically (P >0.05) as well as clinically (mean growth velocity 0.6 cm/year), while height of these patients increased from a mean of 112.7 ± 11.5 cm at the start of therapy to 116.8 ± 11 cm after therapy for one year, which, although statically not significant (P >0.05), was of clinical significance as it makes rate of increase, i.e. the mean growth velocity, 4.1 cm/year close to the normal growth velocity, which is 5 cm/year, before puberty. rhGH therapy for patients with ESRD on regular hemodialysis is helpful in height gain and catch-up growth even when given three-times per week instead of five- or six-times per week. We recommend giving rhGH therapy as a routine supplementation to pediatric patients before epiphyseal closure.

Changes in plasma FGF23 in growth hormone deficient children during rhGH therapy

Children with growth hormone deficiency (GHD) have increased renal phosphorus reabsorption during rhGH therapy, Fibroblast growth factor 23 (FGF23) is a known regulator of serum phosphorus and may be responsible for this effect. Prospective study in GHD children investigating changes in plasma C-terminal FGF23 (C-FGF23), markers of mineral metabolism, and insulin-like growth factor (IGF-1) in the first year of rhGH therapy. Normal stature children served as baseline controls. The two groups at baseline were similar, except GHD patients had lower baseline TmP/GFR vs. controls (p < 0.05). C-FGF23 in GHD patients trended upward at follow-up 1 (p = 0.058) and significantly increased at follow-up 2 (p = 0.0005) compared to baseline. TmP/GFR also rose at follow-up 1 (p = 0.002) and follow-up 2 (p = 0.027). The C-FGF23 rise persisted after adjusting for age, gender, sex, total calcium, and phosphorus (p < 0.01) but attenuated after adjusting for TmP/GFR or IGF-1. C-FGF23 rises during rhGH therapy in spite of increased Tmp/GFR, an unanticipated observation given the role of FGF23 as a phosphaturic factor. The C-FGF23 rise may be a secondary response during rhGH therapy.

First-year response to rhGH therapy in children with CKD: a National Cooperative Growth Study Report

A clear definition of the appropriate growth response during recombinant human growth hormone (rhGH) treatment has never been established in the pediatric chronic kidney disease (CKD) population. We present here data from Genentech's National Cooperative Growth Study (NCGS) on the first-year growth response in prepubertal children with CKD. Using NCGS data, we constructed response curves for the first year of rhGH therapy in 270 (186 males, 84 females) naïve-to-treatment, prepubertal children with CKD prior to transplant or dialysis. Data from both genders were combined because gender was not significantly related to height velocity (p = 0.51). Response to rhGH was expressed as height velocity (HV) in cm/year. Mean, mean + or - 1SD, and mean - 2SD for HV during the first year of rhGH treatment as well as pretreatment HV were plotted versus age. Age-specific HV plots for rhGH-treated children with CKD are presented. At all ages, the first-year mean HV was greater than the mean pretreatment HV. The mean - 2SD for HV in children on rhGH treatment was similar to the mean pretreatment HV. These growth plots will be useful to clinicians for assessing a patient's first-year growth response. We propose that a HV below the mean - 1SD is an inadequate response. These curves may help identify patients with a suboptimal growth response due to confounding medical factors and/or non-compliance.

Different effects of short- and long-term recombinant hGH administration on ghrelin and adiponectin levels in GH-deficient adults.

To evaluate circulating levels of ghrelin and adiponectin (ApN) in GH-deficient (GHD) adults before and after short- and long-term recombinant human GH (rhGH) administration. Twenty-three patients were studied. Seventeen subjects (Group A, 12 men, five women) were evaluated at baseline and after 1 year rhGH therapy (dose mean +/- SD: 0.3 +/- 0.1 mg/day) with the assessment of serum IGF-I, ghrelin, ApN, leptin, insulin and glucose levels, percentage of body fat (BF%), HOMA-IR and QUICKI. Seventeen age-, sex- and body mass index (BMI)-matched healthy subjects were recruited for comparisons. Six patients (Group B, three men, three women) underwent IGF-I generation test (rhGH 0.025 mg/kg/day for 7 days), blood sampled at baseline and on day 8 for determination of IGF-I, ghrelin and ApN levels. Group A: at baseline GHD patients showed low IGF-I levels and BF% significantly higher than controls (31.4 +/- 2.5 vs. 26.4 +/- 1.3, P < 0.05). Glucose, insulin, leptin, tryglicerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels, as well as HOMA-IR and QUICKI values were similar in the two series, while total cholesterol levels were higher in GHD. In GHD, ghrelin levels were significantly lower than in controls (193.9 +/- 27.1 vs. 298.1 +/- 32.5 pmol/l, respectively, P = 0.02), while ApN levels were similar (10.2 +/- 1.1 and 9 +/- 1 mg/l, respectively, P = ns). After 1 year of rhGH therapy, BF%, BMI, serum total and LDL cholesterol significantly decreased, serum leptin levels showed a trend to decrease, while HOMA-IR and QUICKI did not change. Ghrelin and ApN levels significantly increased from 193.9 +/- 27.1 to 232.4 +/- 26.3 pmol/l (P < 0.01) and from 8.6 +/- 0.8 to 10.3 +/- 1.1 mg/l (P < 0.05), respectively. In group B, the expected increase in IGF-I levels was associated with a significant decrease in ghrelin levels, while ApN did not change. GHD patients showed serum ghrelin lower than controls, probably due to the higher BF%. No difference in ApN was observed. Ghrelin and ApN increments induced by long-term treatment may be related to the significant BMI and BF% reduction that is the predominant metabolic effect of rhGH therapy. Conversely, the decrease in ghrelin levels observed after short-term rhGH administration may be consistent with an inhibitory feedback of GH and/or IGF-I on ghrelin release.

Expression of insulin target genes in skeletal muscle and adipose tissue in adult patients with growth hormone deficiency: effect of one year recombinant human growth hormone therapy.

Our aim was to investigate the effects of one year recombinant human growth hormone (rhGH) therapy on the regulation by insulin of gene expression in muscle and adipose tissue in adults with secondary GH deficiency (GHD). Six GHD subjects without upper-body obesity were submitted to a 3-h euglycemic hyperinsulinemic clamp before and after one year of rhGH therapy. Muscle and abdominal subcutaneous adipose tissue biopsies were taken before and at the end of each clamp. The mRNA levels of insulin receptor, p85 alpha-phosphatidylinositol-3 kinase (p85 alpha PI-3K), insulin dependent glucose transporter (Glut4), hexokinase II, glycogen synthase, lipoprotein lipase (LPL) in muscle and in adipose tissue, hormone sensitive lipase and peroxisome proliferator-activated receptor gamma (PPAR gamma) in adipose tissue were quantified by RT-competitive PCR. One year treatment with rhGH (1.25 IU/day) increased plasma IGF-I concentrations (54+/-7 vs 154+/-11 ng/ml, P<0.01) but did not affect insulin-stimulated glucose disposal rate measured during the hyperinsulinemic clamp (74+/-9 vs 85+/-5 micromol/kg free fat mass/min). Insulin significantly increased p85 alpha PI-3K, hexokinase II and Glut4 mRNA levels in muscle both before and after rhGH treatment. One year of GH therapy increased LPL mRNA levels in muscle (38+/-2 vs 70+/-7 amol/microg total RNA, P<0.05) and in adipose tissue (2490+/-260 vs 4860+/-880 amol/microg total RNA, P<0.05), but did not change the expression of the other mRNAs. We conclude from this study that GH therapy did not alter whole body insulin sensitivity and the response of gene expression to insulin in skeletal muscle of adult GHD patients, but it did increase LPL expression in muscle and adipose tissue. This result could be related to the documented beneficial effect of GH therapy on lipid metabolism.

Weight relative to height before and during growth hormone therapy in prepubertal children.

We used the Genentech National Cooperative Growth Study database to examine differences in weight relative to height (weight for height standard deviation score or WTHTZ) in 3460 patients at enrollment and after one year of therapy with recombinant human growth hormone (rhGH), and in a subset of 450 patients treated for three years with rhGH. The major diagnostic categories were idiopathic growth hormone deficiency (IGHD), organic GH deficiency (OGHD), and idiopathic short stature (ISS). Children with IGHD and ISS were underweight for height at baseline but had a progressive increase in WTHTZ during three years of rhGH therapy. The same pattern applied to children with IGHD associated with septo-optic dysplasia and CNS trauma or infection. However, children with OGHD associated with craniopharyngiomas, other CNS tumors, leukemia, or CNS irradiation were overweight when starting rhGH and showed a decrease in WTHTZ during the first year of rhGH therapy. The increase in WTHTZ during rhGH treatment in children with ISS and OGHD suggests that the GH-induced increase in muscle mass exceeded loss of fat mass. Because children with neoplasm-related OGHD were overweight at baseline, the decline in WTHTZ during the first year of rhGH therapy suggests that loss of fat mass is the predominant effect in this subgroup.

Long-Term Growth Hormone Treatment of Growth Retarded Children With Chronic Renal Insufficiency (CRI) † 1798

One hundred twenty-five patients were enrolled in a study of growth retarded pre-pubertal (at baseline) children with CRI and were randomized to recieve either rhGH 0.5 mg/kg/day SC or an equal volume of placebo for two years. After two years all patients received rhGH. Treatment was paused in 24 children after reaching mid-parental target height percentile, of whom 17(71%) required re-initiation of rhGH because of a substantial decrease in standardized height. Long-term (5 year) treatment of 35 children led to a significant (p<0.0001) improvement in standardized height from -2.8 at baseline to -0.9 at 5 years. Adult height potential was not adversely impacted with a Δ height age minus Δ bone age at 5 years of +0.3 (N=21). The mean calculated creatinine clearance decreased from 36.2 ± 19.0 mL/min/1.73m2 at baseline to 27.2 ± 18.8 mL/min/1.73m2 at 5 years (p=.0007) which would be consistent with the natural history of CRI children. There was a small increase in the median fasting and 2 hour post-prandial plasma insulin levels during treatment. Development of avascular necrosis of the femoral head, a known compliction of renal osteodystropy was observed in several patients. Presence of AVN was noted on hip x-rays prior to initiation of rhGH in three patients. Because baseline x-rays were not available for most patients this finding requires further investigation. Forty-eight patients had renal transplants and 42 were treated with growth hormone prior to transplant. Thirty patients (23M, 7F) received at least 2 years of rhGH therapy before transplant. Their mean±SD Ht SDS was -2.8± 0.9 at baseline and -1.2 ± 1.2 at transplant. This is a significant (p<0.0001) mean improvement of 1.6 ± 1.0 in Ht SDS after a mean of 4.3 ± 1.7 yr. of rhGH therapy. Long-term rhGH treatment in children with CRI improves the potential of children with CRI achieving target adult height.

Growth hormone therapy with three dosage regimens in children with idiopathic short stature

Objective: In children with idiopathic short stature (ISS) we studied the growth-promoting effect at 4 years of recombinant human growth hormone (rhGH) therapy in three dose regimens and evaluated whether increasing the dosage after the first year could prevent a decline in height velocity (HV). Design: Included were 223 patents who were treated with subcutaneous administrations of rhGH 6 days per week. They were randomized to three groups: 3 IU/m 2 body surface/day, 4.5 IU/m 2/day, and 3 IU/m 2/day during the first year and 4.5 IU/m 2/day thereafter, corresponding with dosages of 0.2 and 0.3 mg/kg body weight/week, respectively. Growth was compared with a standard of 229 untreated children with ISS [ISS standard]. Results: During the first year of treatment HV almost doubled and was higher with 4.5 IU/m 2 than with 3 IU/m 2. In the second year HV no longer differed among the groups, but increasing the dosage slowed the rate of the fall of HV. During 4 years of therapy the height SD score for age increased by a mean (SD) of 2.5 (1.0) [ISS standards], or 1.2 (0.7) (British standards), bone age increased by 4.8 (1.3) years, and predicted adult height SD score increased by 1.5 (0.7). After 4 years the results of the group with 4.5 IU/m 2 were slightly better than those of the other groups. When dropouts were included in the analysis (assuming a stable height SD score after discontinuation of rhGH therapy), height gain was still significant. Conclusions: During 4 years of rhGH therapy, growth and final height prognosis improved, slightly more with 4.5 IU/m 2 than with 3 IU/m 2 or 3 to 4.5 IU/m 2. However, bone age advanced on average 4.8 years during this period; therefore, any effect on final height will probably be modest. (J Pediatr 1998;132:455-60)

Effects of recombinant human growth hormone on renal function in children with renal transplants

OBJECTIVE: To provide accurate measurement of renal function during treatment with recombinant human growth hormone (rhGH). METHODS: We measured glomerular filtration rate and effective renal plasma flow by clearance of inulin and para-aminohippuric acid before rhGH therapy, after 1 week, and then at 6-month intervals for up to 2 years of treatment in 16 children (mean [SD] age = 13.1 [2.2] years; glomerular filtration rate = 52 [27] ml/min per 1.73 m 2). The mean (SD) time from transplantation was 6.5 (3.6) years. RESULTS: Linear growth velocity during rhGH therapy increased from 4.0 (1.8) to 8.8 (2.6) cm/yr ( p <0.0001). One child was withdrawn after 9 months because of abnormal glucose tolerance, and another child received a second renal transplant after 18 months. Glomerular filtration rate increased to 57 (29) ml/min per l.73 m 2 at 1 week ( p = 0.004), remained improved at 6 months (63 [30]; p = 0.013), but was not significantly better at 1 year (59 [33]). Effective renal plasma flow on day 1 was 237 (127) ml/min per 1.73m 2 and was unchanged on day 8 (244 [123]), at 6 months (271 [149]), and after 1 year (269 [157]). During the study there was no significant change in filtration fraction, blood pressure, or kidney volume, and excretion of microalbumin and N -acetylglucosaminidase was unaltered. There was one rejection episode per 14.8 patient-months in the year before treatment, 1 per 18.9 patient-months during the first year of treatment, and 1 per 13 patient-months during the second year of rhGH therapy. CONCLUSION: Treatment with rhGH improves growth in children with renal transplants. Glomerular filtration rate was increased after 1 week and 6 months of rhGH therapy but returned to baseline values thereafter. The data indicate the need for long-term follow-up of children with renal transplants who are receiving rhGH. (J P EDIATR 1996;128:177-83)

Efficacy and safety of growth hormone treatment in short children with renal allografts: Three year experience

The majority of children with renal allografts have diminished growth and reduced final height. Impaired allograft function and glucocorticoid treatment are the main contributing factors. Since recombinant human growth hormone (rhGH) treatment was able to counteract the growth depressing effects of glucocorticoids in experimental uremia, an open-labeled prospective study in 17 short children with renal allografts was designed to investigate the efficacy of rhGH therapy (30 IU/m2/week) with special emphasis on the safety regarding graft function and carbohydrate metabolism. Height velocity in prepubertal children (N = 10) increased from baseline median 2.2 cm/year to 7.9 cm/year after one year (P < 0.01), 7.2 cm/year after two years (P < 0.01), and 5.5 cm/year (P < 0.05) after three years of rhGH therapy. This resulted in a normalization of height in three out of seven patients after two years and in three out of five after three years of therapy. Growth stimulation in pubertal children was less consistent. Bone maturation paralleled chronological age. The effect of rhGH treatment on longitudinal growth may be partially attributable to the improved ratio between the serum concentration of the insulin-like growth factor (IGF)-I and its major binding protein (BP) IGFBP-3 leading to a normal IGF bioactivity. The incidence of acute rejection crises in the study group (corrected for time after grafting) did not differ from that of untreated retrospective "controls" (0.10 vs. 0.12 episodes per patient and year). No systematic effect of rhGH on glomerular filtration rate assessed by repeated inulin and creatinine clearances was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of spontaneous or induced puberty on the growth promoting effect of treatment with growth hormone in girls with Turner's syndrome

The aim was to evaluate the effect of 3 years treatment with recombinant human growth hormone (rhGH) on height velocity and height in girls with Turner's syndrome (TS) and to study to influence of spontaneous or induced puberty on the growth promoting effect of rhGH. The investigation was performed in 36 girls with Turner's syndrome treated for 3 years with rhGH in a dose of 1 IU/kg week, administered as daily subcutaneous injections. Fifteen patients remained prepubertal throughout the observation period (Group 1). During the first 2 years of rhGH therapy, four girls developed puberty spontaneously (Group 2). During the 3rd year of rhGH treatment puberty was induced with 100 ng/kg day ethinyl oestradiol orally in 17 girls requesting pubertal development and with a bone age of at least 11 'years' (Group 3). During the first year of rhGH therapy height velocity increased significantly in all patients. Mean +/- SD height velocity was higher in the four patients with Turner's syndrome who developed spontaneous puberty than in 17 age-matched girls with Turner's syndrome without puberty (8.9 +/- 1.2 vs 7.4 +/- 1.2 cm/year; P < 0.05). During the second and third year of rhGH treatment height velocity decreased in all patients but remained above baseline levels. The induction of puberty with 100 ng/kg day ethinyl oestradiol in the patients of Group 3 did not lead to an acceleration of height velocity, but seemed in contrast to decelerate height velocity. After 3 years of rhGH treatment, 21 out of 36 patients have obtained a height at or above the initially calculated projected adult height and five girls are already taller than 150 cm. The onset of spontaneous puberty during the first years of rhGH treatment seems to have an additive effect to rhGH on height velocity. Induction of puberty with oral administration of 100 ng/kg day ethinyl oestradiol did not have any beneficial effect on height velocity and seems therefore not to be the optimal way to induce puberty with an adequate pubertal growth spurt in girls with Turner's syndrome under rhGH therapy. Different doses and routes of oestrogen administration have to be evaluated in order to mimic the growth promoting effect of spontaneous puberty as well as possible.

Biosynthetic Human Growth Hormone in the Treatment of Growth Hormone Deficiency

A total of 309 previously untreated children with growth hormone deficiency (GHD) (219 boys, 90 girls; mean age 8.4 +/- 3.9 years, range 1.5-19 years) were treated for up to 3 years in an ongoing trial designed to examine the long-term efficacy and safety of biosynthetic somatropin (rhGH). The children were treated with rhGH, 0.06 mg/kg (0.16 IU/kg) three times weekly. In the prepubertal children, the mean height velocity increased during the first year from 3.8 +/- 1.8 cm/year to 8.9 +/- 2.2 cm/year (n = 188). During the second and third years, their height velocities were 7.1 +/- 1.1 (n = 147) and 6.3 +/- 1.2 cm/year (n = 64), respectively. The height velocity SDS increased from -2.5 +/- 1.9 before treatment to 3.1 +/- 2.6 during the first year of treatment in the prepubertal children. The mean pretreatment height velocity in those with idiopathic GHD (3.8 +/- 1.6 cm/year) did not differ from that in children with organic GHD (3.8 +/- 2.3 cm/year). In addition, the height velocities during the first year of therapy did not differ significantly with respect to the aetiology of GHD. For the children who entered puberty during the study, the mean height velocity increased from 3.0 +/- 1.7 cm/year before treatment to 8.4 +/- 2.3 cm/year during the first year of rhGH therapy. In the first year, the height velocity of children with a bone age of less than 5 years (9.4 +/- 2.3 cm/year) was significantly greater than that in children with a bone age of 5-10 years (8.4 +/- 1.8 cm/year) or greater than 10 years (7.8 +/- 2.2 cm/year: p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)