Effect of growth hormone, glutamine, and diet on adaptation in short-bowel syndrome: a randomized, controlled study. Low-dose recombinant human growth hormone increases body weight and lean body mass in patients with short bowel syndrome. Low-dose growth hormone in adult home parenteral nutrition-dependent short bowel syndrome patients: a positive study. Effect of high dose growth hormone with glutamine and no change in diet on intestinal absorption in short bowel patients: a randomised, double blind, crossover, placebo controlled study. A multicenter, randomized, double-blind, placebo-controlled trial to evaluate the metabolic and respiratory effects of growth hormone in children with cystic fibrosis. Beneficial effects of extended growth hormone treatment after hospital discharge in pediatric burn patients. The growth and cardiovascular effects of high dose growth hormone therapy in idiopathic short stature. Growth hormone, glutamine, and an optimal diet reduces parenteral nutrition in patients with short bowel syndrome: a prospective, randomized, placebo-controlled, double-blind clinical trial. Improvement in growth after 1 year of growth hormone therapy in well-nourished infants with growth retardation secondary to chronic renal failure: results of a multicenter, controlled, randomized, open clinical trial.
The effects of parenteral growth hormone, glutamine supplementation, and a high carbohydrate-low fat (HCLF) diet on gut adaptation in short-bowel syndrome are unclear. The aim of this study was to compare effects of this treatment regimen and placebo in patients with short-bowel syndrome.
                A randomized, 6-week, double-blind, placebo-controlled, crossover study in 8 patients with short-bowel syndrome (average small bowel length, 71 cm; mean duration, 12.9 years) was performed. Active treatment was growth hormone (0.14 mg.kg-1.day-1), oral glutamine (0.63 g.kg-1.day-1), and the HCLF diet for 21 days. The weight, basal metabolic rate, nutrient and electrolyte balance, serum insulin-like growth factor I levels, D-xylose absorption, morphology and DNA proliferation of small intestinal mucosa, and gastrointestinal transit were evaluated. Treatments were compared by paired t test.
                Active treatment transiently increased body weight, significantly but modestly increased the absorption of sodium and potassium, and decreased gastric emptying. The assimilation of macronutrients, stool volumes, and morphometry of small bowel mucosa were not statistically different in the two treatment arms.
                Although treatment with growth hormone, glutamine, and HCLF diet for 3 weeks resulted in modest improvements in electrolyte absorption and delayed gastric emptying, there were no improvements in small bowel morphology, stool losses, or macronutrient absorption. The authors investigate the effects of low dose recombinant human growth hormone (rhGH) on body composition and absorptive capacity in patients with short bowel syndrome from Crohn's disease.
                Patients with short bowel syndrome usually are malnourished because of malabsorption. The anabolic effects of high doses of rhGH have been tested in different clinical catabolic conditions, recently including patients with short bowel syndrome. The authors have investigated the effects of low-dose rhGH in short bowel syndrome in a placebo-controlled crossover clinical trial.
                Ten patients were treated with daily subcutaneous doses of rhGH/placebo (0.5 international units/kg-1 per week-1 = 0.024 mg/kg-1 per day-1) for 8 weeks in a randomized, double-blind, placebo-controlled crossover clinical trial with a minimum of 12 weeks wash-out. Absorptive capacity and biochemical parameters were investigated in a metabolic ward before treatment and during first and last week of treatment. Body composition was determined by DEXA-Scan (Lunar DPX, Scanexport Medical, Helsingborg, Sweden), impedance analysis, and whole body potassium counting.
                Low-dose rhGH doubled serum levels of insulin-like growth factor-1 (IGF-1) and increased body weight, lean body mass, and total body potassium by 5% (p < 0.05). Fat-free mass and total body water increased by 6% (p = 0.008). Increases in IGF-1 levels correlated with increases in fat-free mass (r = 0.77, p < 0.02). No significant changes in absorptive capacity of water, energy, or protein were detected.
                Eight weeks of low-dose rhGH treatment leads to increases in body weight, lean body mass, and fat-free mass in patients with short bowel syndrome, correlated to increases in IGF-1 levels. Controversy surrounds a 3-week treatment with a high-dose (0.14 mg. kg(-1). day(-1)) growth hormone (GH), glutamine, and high carbohydrate diet in home parenteral nutrition (HPN)-dependent patients with short-bowel syndrome (SBS). This study assessed treatment with low-dose GH in these patients.
                Twelve adult HPN-dependent (duration, 7 +/- 1 years; mean +/- SEM) patients with SBS (small-bowel remnant length, 48 +/- 11 cm) who were on an unrestricted hyperphagic diet were randomized in a double-blind, placebo-controlled, crossover study. Patients received daily low-dose GH (0.05 mg. kg(-1). day(-1)) and placebo for two 3-week periods separated by a 1-week washout period. Net intestinal absorption of macronutrients was assessed using a duplicate diet; nutritional assessment and blood tests were performed. Data from each group were compared using Wilcoxon rank sum test.
                Treatment with GH increased intestinal absorption of energy (15% +/- 5%, P < 0.002), nitrogen (14% +/- 6%, P < 0.04), carbohydrates (10% +/- 4%, P < 0.04), and fat (12% +/- 8%, NS). The increased food absorption represented 37% +/- 16% of total parenteral energy delivery. Body weight (P < 0.003), lean body mass (P < 0.006), D-xylose absorption (P < 0.02), insulin-like growth factor 1 (P < 0.002), and insulin-like growth factor binding protein 3 (P < 0.002) increased, whereas uptake of GH binding protein decreased (P < 0.01), without any major adverse effect.
                Three weeks of low-dose GH significantly improved intestinal absorption in HPN-dependent SBS patients who were on a hyperphagic western diet. High dose growth hormone, glutamine, and a high carbohydrate diet may improve intestinal function in short bowel patients.
                To investigate if growth hormone with glutamine and no change in diet improved intestinal function.
                Eight short bowel patients were randomised in a double blind crossover study between placebo and growth hormone (mean 0.12 mg/kg/day) with oral (mean 28 g/day) and parenteral glutamine (mean 5.2 g/day) for 28 days. Balance studies were performed at baseline and five days after placebo and treatment were terminated. Dietary energy, carbohydrate, and fat were maintained as usual.
                Growth hormone with glutamine did not improve intestinal absorption of energy (baseline, placebo, treatment, mean: 46%, 48%, 46% of oral intake, respectively), carbohydrate (71%, 70%, 71%), fat (20%, 15%, 18%), nitrogen (27%, 18%, 19%), wet weight (37%, 39%, 31%), sodium (-16%, -16%, -36%), potassium (43%, 47%, 33%), calcium (-16%, -16%, -15%) or magnesium (-3%, 4%, 2%) compared with placebo or baseline (p>0.05) five days after treatment was terminated. All patients experienced adverse effects.
                Combined high dose growth hormone and glutamine administered for four weeks did not improve intestinal absorption five days after treatment was terminated in short bowel patients on their usual diet. Positive effects of growth hormone therapy on growth, nutritional status, and lung function have been observed in patients with cystic fibrosis, but the current evidence is based on unblinded studies that involved a small number of patients. This trial was designed as a multicenter, randomized, placebo-controlled, double-blind study to assess the efficacy and safety of 2 dosages of growth hormone in cystic fibrosis.
                Sixty-three dystrophic patients with cystic fibrosis were randomly assigned for 24 weeks to 1 of 3 treatment arms: growth hormone dosage of 0.11 IU/kg body weight per day, growth hormone dosage of 0.21 IU/kg body weight per day, or placebo. The 24-week double-blind period was followed by an open treatment period of 24 weeks. The primary outcome measure was the change in forced expiratory volume in 1 second in percentage predicted from baseline. Secondary outcome measures were changes in height, weight, and exercise tolerance.
                Height, growth velocity, and growth factors (insulin-like growth factor 1 and insulin-like growth factor-binding protein 3) increased significantly in both treatment groups, whereas weight gain did not differ between the growth hormone groups and placebo. A trend toward improvement in absolute forced vital capacity was observed in patients who received the higher growth hormone dosage, whereas forced expiratory volume in 1 second did not change significantly with growth hormone treatment. Maximal oxygen uptake during peak exercise increased significantly in treated patients. There were no significant differences in the frequency or severity of adverse effects or in the incidence of abnormalities in glucose metabolism.
                These data suggest that in the group investigated, growth hormone therapy was well tolerated and had positive metabolic effects but did not result in short-term improvement of lung function in patients with cystic fibrosis. To study the efficacy of growth hormone given to severely burned children from discharge to 12 months after burn and for 12 months after the drug was discontinued.
                We have previously shown that low-dose recombinant human growth hormone (rhGH), given to children after a severe thermal injury, successfully improved lean muscle mass, bone mineral content, and growth. The aim of the present study was to investigate long-term functional improvements after treatment.
                Forty-four pediatric patients with over 40% total body surface area burns were studied for 24 months after burn. Patients were randomized to receive either rhGH (0.05 mg/kg body weight) or placebo. Height, weight, body composition, serum hormones, resting energy expenditure, cardiac function, muscle strength, and number of reconstructive procedures performed were measured during rhGH treatment and for 12 months after treatment was discontinued. Statistical analysis used Tukey's multiple comparison test. Significance was accepted at P < 0.05.
                Height, weight, lean body mass, bone mineral content, cardiac function, and muscle strength significantly improved during rhGH treatment compared with placebo (P < 0.05). This treatment significantly increased GH, IGF-I, and IGFBP-3, whereas serum cortisol decreased (P < 0.05). The number of operative reconstructive procedures was significantly lower with rhGH (P < 0.05). Improvements in height, bone mineral content, and IGF-1 concentrations persisted after rhGH treatment (P < 0.05). No side effects with rhGH were observed.
                Administration of rhGH for 1 year after burn was safe and improved recovery. These salutary effects continued after rhGH treatment was discontinued. It is possible that high dose GH treatment may have beneficial effects on growth but important adverse effects on cardiac function. We have therefore investigated the efficacy and cardiovascular effects of high dose biosynthetic human GH (r-hGH) treatment in children with idiopathic short stature and a normal pretreatment height velocity.
                Randomized controlled study.
                Twenty-nine short (height SDS < 1.5), normally growing (height velocity SDS > -1.5), prepubertal children referred to two specialist growth clinics.
                Children were randomly assigned to an observation group or to receive 'standard' (20 IU/m2/week) or 'high' (40 IU/m2/week) dose r-hGH by daily subcutaneous injection. At the end of 1 year the observation group were randomly assigned to 'standard' or 'high' dose r-hGH therapy for the second year of the study. Regular growth, biochemical and echocardiographic monitoring were performed throughout the study period.
                Changes in height velocity, HtSDS for bone age (HtSDSBA), left ventricular mass index (LVMI) and left ventricular function (fractional shortening) during 2 years treatment.
                Twenty-seven children completed the study. Ht velocity SDS increased with r-hGH therapy in a dose dependent fashion. First-year height velocity SDS was +5.7 in the high dose r-hGH group compared with +2.7 in the standard dose r-hGH group and -0.5 in the observation group (P < 0.001). In those children treated for 2 years HtSDSBA was -0.5 in the high dose group but had not changed significantly in the standard dose group (-1.7) (P = 0.01). After one year r-hGH treatment LVMI was 71 g/m2 (observation group), 73 g/m2 (20 IU/m2/week group) and 74 g/m2 (40 IU/m2/week group) (P = 0.77). LVMI increased significantly from baseline to 76 g/m2 after 2 years therapy with 40 IU/m2/week r-hGH (P = 0.04) but nevertheless remained within the normal range. Fractional shortening did not change significantly over 2 years of r-hGH therapy.
                High dose (40 IU/m2/week) r-hGH treatment of children with idiopathic short stature resulted in a greater short-term acceleration in growth rate than 'standard' dose therapy without an excessive advance in skeletal maturity and probably represents the optimal growth promoting dose for short, normally growing children. Whether continued high dose r-hGH therapy increases final height requires further study. Left ventricular morphology and function remained within the normal range during r-hGH therapy but regular monitoring of cardiovascular status should continue in non-GHD children receiving r-hGH in high doses over a longer time period. To determine if growth hormone (GH) and glutamine (Gln) might allow for a reduction in parenteral nutrition (PN) in individuals with short bowel syndrome.
                Following massive intestinal resection, patients frequently sustain severe nutrient malabsorption and are dependent on PN for life. GH treatment with or without Gln might allow for a reduction in PN.
                A prospective, double-blind, randomized, placebo-controlled clinical trial performed in 41 adults dependent on PN. Following screening, patients were admitted to an in-house facility for 6 weeks. After 2 weeks of stabilization and dietary optimization, patients were randomized to one of 3 treatment arms (1:2:2 ratio): oral Gln (30 g/day) + GH placebo (control group, n = 9), Gln placebo + GH (0.1 mg/kg per day, n = 16), or Gln + GH (n = 16). Standard criteria based on clinical and laboratory measurements were followed to determine PN volume and content. After 4 weeks of treatment, patients were discharged and monitored; GH and GH placebo were discontinued, but the diet with Gln or Gln placebo was continued for 3 months.
                Patients receiving GH + Gln placebo + diet showed greater reductions in PN volume (5.9 +/- 3.8 L/wk, mean +/- SD), PN calories (4338 +/- 1858 calories/wk), and PN infusions (3 +/- 2 infusions/wk) than corresponding reductions in the Gln + diet group (3.8 +/- 2.4 L/wk; 2633 +/- 1341 calories/wk; 2 +/- 1 infusions/wk, P < 0.05). Patients who received GH + Gln + diet showed the greatest reductions (7.7 +/- 3.2 L/wk; 5751 +/- 2082 calories/wk; 4 +/- 1 infusions/wk, P < 0.001 versus Gln + diet). At the 3-month follow-up, only patients who had received GH + Gln + diet maintained significant reductions in PN (P < 0.005) compared with the Gln + diet.
                Treatment with GH + diet or GH + Gln + diet initially permitted significantly more weaning from PN than Gln + diet. Only subjects receiving GH + Gln + diet maintained this effect for at least 3 months. Our aim was to evaluate the growth-promoting effect of growth hormone (GH) treatment in infants with chronic renal failure (CRF) and persistent growth retardation despite adequate nutritional and metabolic management.
                The study design included randomized, parallel groups in an open, multicenter trial comparing GH (0.33 mg/kg per wk) with nontreatment with GH during 12 months. Sixteen infants who had growth retardation, were aged 12+/-3 months, had CRF (GFR<or=60 ml/min per 1.73 m2), and had adequate nutritional intake and good metabolic control were recruited from eight pediatric nephrology departments from Spain and Portugal. Main outcome measures were body length, body weight, bone age, biochemical and hormonal analyses, renal function, bone mass, and adverse effects.
                Length gain in infants who were treated with GH was statistically greater (P<0.05) than that of nontreated children (14.5 versus 9.5 cm/yr; SD score 1.43 versus -0.11). The GH-induced stimulation of growth was associated with no undesirable effects on bone maturation, renal failure progression, or metabolic control. In addition, GH treatment improved forearm bone mass and increased serum concentrations of total and free IGF-I and IGF-binding protein 3 (IGFBP-3), whereas IGF-II, IGFBP-1, IGFBP-2, GH-binding protein, ghrelin, and leptin were not modified.
                Infants with CRF and growth retardation despite good metabolic and nutritional control benefit from GH treatment without adverse effects during 12 months of therapy.
The results suggest a positive effect of human growth hormone on weight gain and energy absorption. However, in the majority of trials, the effects are short-lived returning to baseline shortly after cessation of therapy. The temporary benefit calls into question the clinical utility of this treatment.  To date, the evidence is inconclusive to recommend this therapy.  Consideration should be made to studying patients during the active phase of intestinal adaptation rather than in the setting of chronic intestinal failure.  The role of HGH in paediatric short bowel syndrome remains unknown.