rhGH Group Research Articles

Growth after recombinant human growth hormone treatment in children with chronic renal failure: Report of a multicenter randomized double-blind placebo-controlled study

Objective: To determine whether treatment with recombinant human growth hormone (rhGH) enhances growth rate in growth-retarded children with chronic renal failure. Design: One hundred twenty-five prepubertal growth-retarded children with chronic renal failure were randomly assigned to receive either rhGH (n = 82) or placebo (n = 43) for 2 years. Setting: The study was undertaken at 17 pediatric nephrology centers in the United States. Measurements: Growth rate, standardized height, bone age, fasting and 2-hour postprandial glucose and insulin levels, biochemical values, and insulin-like growth factor I and anti-growth hormone antibody levels were evaluated serially during the 2-year study period. Results: Standardized height increased from −2.94 to −1.55 in the rhGH group after 24 months of treatment, and decreased from −2.82 to −2.91 in the placebo group ( p <0.00005). Patients in the rhGH group who completed 24 months of study (n = 55) had a greater growth rate during the first year (10.7 ± 3.1 cm/yr) than during the second year (7.8 ± 2.1 cm/yr) of treatment. These growth rates were significantly greater than those in the placebo group (n = 27) in the first (6.5 ± 2.6 cm/yr) and second (5.5 ± 1.9 cm/yr) years ( p <0.00005 for both years). The mean Δ height age minus the Δ bone age was positive in the rhGH group, suggesting improved final height potential. There was no significant difference in the change in calculated creatinine clearance over baseline values in the rhGH group from that in the placebo group after 24 months of study ( p = 0.63). Mean fasting and postprandial insulin values were elevated at 12 months but not at 24 months in the rhGH-treated patients. Mean fasting and 2-hour postprandial glucose values at 24 months were not significantly elevated over baseline values in either group. Conclusions: Growth rate and standardized height were significantly increased in growth-retarded prepubertal children with chronic renal failure when rhGH was used. The acceleration in growth was not associated with undue advancement of bone age. No clinically significant side effects were associated with rhGH treatment. The use of rhGH in growth-retarded children with chronic renal failure may facilitate the achievement of the inherent growth potential of such children. (J P ediatr 1994;124:374-82)

HUMAN GROWTH HORMONE (GH) TREATMENT OF IMMATURE MALE MONKEYS FOR SIX MONTHS

Little is known about the effect of exogenous GH to accelerate or disrupt statural development in normally growing primates. Prepubertal male rhesus monkeys were injected for 2 months with placebo (sc daily) and then randomized to treatment groups by body weight (BW). They were then treated daily with placebo or recombinant human GH (rhGH) at 0.05 or 0.35 mg/kg for 6 months. The placebo monkeys grew as expected, with significant increases in BW gain, tibial length, skeletal maturation score (SMS) and crown-rump length (CRL); these also had a stable IGF-1 baseline. Both groups treated with rhGH had significant increases in BW, while only the high dose group had an increase in CRL (+31%) greater than placebo controls. The IGF-1 areas under the treatment curves were also elevated above placebo in the rhGH groups (+46% & +51%). There were no anti-rhGH antibodies measured in the high rhGH dose monkeys. No group differences were observed in fasting insulin, glucose, cortisol, testosterone, triglycerides, urea nitrogen, cholesterol, albumin, calcium, alkaline phosphatase or alanine transaminase. We conclude that this rhGH treatment regimen over 6 mo did not disrupt the normal growth pattern of prepubertal monkeys. Daily exposure to rhGH enhanced BW gain, CRL and IGF-1 levels. Changes in tibial length and SMS were not different from placebo controls.

Growth hormone treatment in growth hormone-deficient adults. II. Effects on exercise performance

Growth hormone (GH) treatment in adults with GH deficiency increases lean body mass and thigh muscle cross-sectional area. The functional significance of this was examined by incremental cycle ergometry in 24 GH-deficient adults treated in a double-blind placebo-controlled trial with recombinant DNA human GH (rhGH) for 6 mo (0.07 U/kg body wt daily). Compared with placebo, the rhGH group increased mean maximal O2 uptake (VO2max) (+406 +/- 71 vs. +133 +/- 84 ml/min; P = 0.016) and maximal power output (+24.6 +/- 4.3 vs. +9.7 +/- 4.8 W; P = 0.047), without differences in maximal heart rate or ventilation. Forced expiratory volume in 1 s, vital capacity, and corrected CO gas transfer were within normal limits and did not change with treatment. Mean predicted VO2max, based on height and age, increased from 78.9 to 96.0% in the rhGH group (compared with 78.5 and 85.0% for placebo; P = 0.036). The anaerobic ventilatory threshold increased in the rhGH group (+159 +/- 39 vs. +1 +/- 51 ml/min; P = 0.02). The improvement in VO2max was noted when expressed per kilogram body weight but not lean body mass or thigh muscle area. We conclude that rhGH treatment in adults with GH deficiency improves and normalizes maximal exercise performance and improves submaximal exercise performance and that these changes are related to increases in lean body mass and muscle mass. Improved cardiac output may also contribute to the effect of rhGH on exercise performance.

Growth hormone treatment in growth hormone-deficient adults. I. Effects on muscle mass and strength

The effect of recombinant DNA human growth hormone (rhGH) treatment in adults with growth hormone (GH) deficiency was studied in 24 patients in a double-blind placebo-controlled trial. The dose was 0.07 U/kg body wt daily. After 6 mo of treatment, significant increases were noted in the rhGH group for total cross-sectional area of thigh muscle (+11.2 +/- 3.1 vs. -0.5 +/- 3.0 cm2; P = 0.015 vs. placebo) and quadriceps muscle (+4.1 +/- 0.8 vs. +0.4 +/- 1.2 cm2; P = 0.031) measured by computerized tomography. Strong correlations were noted between lean body mass (measured as total body potassium) and total thigh muscle area in normal and GH-deficient adults both before and after rhGH treatment. Strength of hip flexors (+1.25 +/- 0.27 vs. +0.25 +/- 0.12 z-scores; P = 0.004) and limb girdle muscles increased (P = 0.02) in the rhGH group. We conclude that 1) rhGH increases lean tissue and skeletal muscle mass in adults with human GH deficiency, 2) this suggests a role for GH in the regulation of body composition of adult humans, 3) the increase in strength of limb girdle muscles after rhGH treatment suggests that adults with GH deficiency may have a proximal myopathy, and 4) the failure to demonstrate an increase in strength in other muscle groups may require the study of larger numbers of patients.

A short course of recombinant human growth hormone treatment stimulates osteoblasts and activates bone remodeling in normal human volunteers

The effects of recombinant human growth hormone (rhGH) on biochemical markers of bone turnover and bone mineral content (BMC) were investigated in 20 normal male volunteers (aged 22-31 years) randomized to treatment for 7 days with either rhGH (0.1 IU/kg subcutaneously twice a day) or placebo. Serum somatomedin C rose during treatment (p less than 0.001) but was not significantly different from baseline at day 14. The fasting urinary hydroxyproline/creatinine (p less than 0.001) and calcium/creatinine ratios (p less than 0.01) increased during treatment and remained elevated for 4 and 2 weeks, respectively. Serum bone gamma-carboxyglutamic acid-containing protein (BGP) increased during treatment (p less than 0.001) and remained elevated for 6 months (p less than 0.02). Serum bone alkaline phosphatase (B-AP), after an initial fall in the treatment period (p less than 0.001), increased slightly in the following months (p less than 0.01). In the rhGH group BMC was significantly higher than the prestudy value at day 14 (p less than 0.05) but was unaltered at the end of study. The simultaneous increase in markers of bone resorption and formation during rhGH treatment followed by a decline in resorption parameters within a few weeks and the prolonged effect on BGP and B-AP demonstrate that rhGH treatment stimulates osteoblasts and activates bone remodeling.