Effects on Growth and Metabolism of Growth Hormone Treatment for 3 Years in 36 Children with Prader-Willi Syndrome

Abstract

Background/Aims: Prader-Willi syndrome (PWS) is a complex genetic disorder whose many manifestations include obesity and short stature. Diabetes, osteoporosis, and scoliosis are common. We evaluated the effects of human growth hormone (hGH). Methods: A prospective cohort study of 36 children (1–15 years of age) with genetically confir med PWS who were given hGH (mean dose 0.033 ± 0.006 mg/kg/day) for 36 months. At baseline and once yearly, we evaluated growth, insulin-like growth factor-1 (IGF-1), body composition, bone mineral density (BMD), glucose tolerance, serum lipids, and spinal radiographs. Results: Height gain over the 3-year period was 1.2 SD score. Lean body mass increased significantly during each treatment year. Total body fat decreased by 5.42 and 1.17% in the 1st and 2nd years, respectively. BMD remained unchanged during therapy. IGF-1 and homeostasis model assessment index of insulin resistance increased, and glucose intolerance was found in 22.7% of patients at baseline and 0% at 3 years. None of the patients had diabetes. Their lipid profile improved. Scoliosis was present in 27.8% of the patients at baseline and 47.2% at 3 years. Conclusion: GH treatment in children with PWS has multiple beneficial effects on growth and body composition. Tolerance is good, with an improvement in glucose metabolism, although IGF-1 levels and insulin resistance parameters should be monitored closely. The high rate of scoliosis warrants monitoring by a pediatric orthopedic surgeon.

Growth hormone treatment for two years is safe and effective in adults with Prader-Willi syndrome

“…Proportions as high as 80% has been reported in adolescents with PWS [28]. GH has previous been linked to increased risk of scoliosis during GH treatment in children with PWS, although recent studies have questioned this [29,30]. It is a priory doubtful if GH treatment should worsen scoliosis in adults with closed epiphyseal growth zones.…”

Prader-Willi syndrome

“…33,35 Infants with PWS treated with GH therapy have improvements in head circumference, height, BMI, body composition (with improvement of lean muscle mass and delay of fat tissue accumulation), body proportions, acquisition of gross motor skills, language acquisition, and cognitive scores. [36][37][38][39][40][41][42][43] Older children and adolescents treated with GH therapy not only have the aforementioned physical benefits of the treatment but are also reported to have improvements in behaviors with lack of behavioral deterioration during adolescence. 44 Recent studies have found that up to 72% of children with PWS treated with GH therapy have a serum insulin-like growth factor 1 (IGF-1) level that is >2 standard deviations after 24 months of treatment despite lower doses of GH than are used for children with isolated GH deficiency, which raises concerns about safety issues related to high IGF-1 levels in this population.…”

“…GH treatment normalizes height, increases lean body mass, decreases fat mass, and increases mobility, which are beneficial to weight management. 4,[35][36][37][38][39][41][42][43] Dose recommendations in children are generally similar to those for individuals with isolated GH deficiency, i.e., approximately 1 mg/m2. 42,147 Educational planning should be instigated, and speech therapy is often needed for articulation abnormalities and delays.…”

“…GH replacement therapy to normalize height, increase lean body mass, mobility and activity level, and decrease fat mass is standard of care and can be started at any age. 4,[35][36][37][38][39][41][42][43] Studies thus far have indicated that no age is too early for GH treatment, and the sooner it is started the more benefit it has. 42 It is recommended that a sleep study be performed before initiation of GH therapy to assess for and treat obstructive apnea.…”

Update on Body Composition and Bone Density in Children with Prader-Willi Syndrome

“…Treatment with GHRT improves body composition by increasing lean mass and decreasing fat mass [12,13]. However, while increases in BMD with GHRT have been shown in one study [12], three studies show no change in BMD standard deviation scores or z-scores for the spine and total body [14,15,16]. There are no studies that evaluated bone density for the hips.…”