Three years of growth hormone treatment in young adults with Prader-Willi syndrome: sustained positive effects on body composition.

BACKGROUND: In children with Prader-Willi syndrome (PWS), the benefits of growth hormone treatment are well established. Several one-year studies have shown that growth hormone is also beneficial for adults with PWS, improving body composition. However, little is known about the longer-term effects. This study investigated the effects on body composition in adult patients with PWS during 3 years of growth hormone therapy in a dose of 0.33 mg/m2/day. METHODS: Open-label, prospective study in 43 young adults with PWS with a median (IQR) age of 19.0 (17.5 to 20.7) years. Fat mass percentage SDS and lean body mass SDS were measured annually by DXA. RESULTS: Estimated mean (95% CI) fat mass percentage SDS decreased during the three-year study from 2.1 (1.9 to 2.3) SDS at start to 1.9 (1.8 to 2.1) SDS, p = 0.012, while lean body mass SDS remained stable at - 2.1 (- 2.4 to - 1.8) SDS at start to - 1.9 (- 2.3 to - 1.6) after 3 years, p = 0.15. Fasting glucose and insulin remained similar during the three-year study, glucose being 4.6 (4.4 to 4.8) mmol/l at start and 4.6 (4.5 to 4.7) mmol/l after 3 years of growth hormone, p = 0.93 and insulin being 59.5 (42.2 to 81.5) pmol/l and 55.0 (42.4 to 69.2) pmol/l, resp., p = 0.54. There were no growth hormone-related adverse events during the study. CONCLUSIONS: Three years of growth hormone treatment in young adults with PWS maintains the positive effects on body composition attained during childhood. Thus, adults with PWS benefit from longer-term growth hormone treatment. TRIAL REGISTRATION: EudraCT, EudraCT number 2011-001313-14. Registered 17 October 2012.

Bone mineral density in young adults with Prader-Willi syndrome: A randomized, placebo-controlled, crossover GH trial.

CONTEXT: The prevalence of osteoporosis is increased in adults with Prader-Willi syndrome (PWS). In children with PWS, growth hormone (GH) treatment has beneficial effects on bone mineral density (BMD). BMD might deteriorate after cessation of GH at adult height (AH), while continuing GH might maintain BMD. OBJECTIVE: To investigate the effects of GH vs placebo, and furthermore the effects of sex steroid replacement therapy (SSRT), on BMD in GH-treated young adults with PWS who had attained AH. DESIGN: Two-year, randomized, double-blind, placebo-controlled, crossover GH study. PATIENTS: Twenty-seven young adults with PWS were stratified for gender and BMI and then randomly and blindly assigned to receive GH (0.67 mg/m2 /day) or placebo for 1 year, after which they crossed over to the alternative treatment for another year. MEASUREMENTS: Bone mineral density of the total body (BMDTB ) and lumbar spine (BMDLS ) SDS were measured by dual-energy x-ray absorptiometry. RESULTS: At AH, BMDTB SDS was significantly lower compared to healthy peers (P < .01), while BMADLS SDS was similar. Both BMDTB SDS and BMADLS SDS were similar during 1 year of GH vs 1 year of placebo. In hypogonadal young adults without SSRT, BMDTB SDS and BMADLS SDS decreased during the 2-year study (P = .11 and P = .01), regardless of GH or placebo, while BMDTB SDS increased in those with SSRT (P < .01). CONCLUSIONS: Compared to GH treatment, 1 year of placebo after attainment of AH does not deteriorate BMD SDS in young adults with PWS. In addition, our data suggest that GH is not able to prevent the decline in BMD SDS in hypogonadal young adults with PWS, unless it is combined with SSRT.

Growth Hormone Treatment in Children With Prader-Willi Syndrome: Three Years of Longitudinal Data in Prepubertal Children and Adult Height Data From the KIGS Database.

Context: Longitudinal data of children with Prader-Willi syndrome (PWS) treated with genotropin were registered in the Pfizer International Growth Database (KIGS). Objective: To evaluate efficacy and safety of growth hormone (GH) treatment in a large group of children with PWS. Design: Data registered in KIGS from 1987 to 2012. Setting: Worldwide retrospective cohort study. Patients: Patients included 522 prepubertal children treated with GH for three years and 173 children who had reached adult height. Safety analysis included 2332 children. Intervention involved GH treatment. Main outcome measure: Height standard deviation score (SDS), body mass index (BMI) SDS, occurrence of serious adverse events, and deaths reported in KIGS. Results: In prepubertal children, mean (standard deviation) height SDS improved to -0.31 (1.34) (P < 0.05) during three years of GH treatment. In the adolescent group, height SDS improved until the start of puberty to -0.22 (1.31) (P < 0.05) but had a loss of -0.77 (0.81) during puberty, resulting in a mean adult height SDS of -1.19 (1.37). Total height gain was 0.95 (1.32) SDS. BMI SDS increased in the prepubertal group from 1.11 (2.09) to 1.53 (1.43) (P < 0.05) and did not significantly change in the adolescent group, who had a BMI SDS at an adult height of 1.78 (1.26). KIGS contained 12 death reports. Conclusions: GH treatment in children with PWS significantly improves linear growth. BMI remains on average below +2 SDS, in contrast to the natural course of increasing obesity in PWS. Safety should be closely monitored in children with PWS, with and without GH treatment.

Beneficial Effects of GH in Young Adults With Prader-Willi Syndrome: A 2-Year Crossover Trial.

CONTEXT: Patients with Prader-Willi syndrome (PWS) are severely at risk to develop morbid obesity, diabetes mellitus type 2, and cardiovascular disease, leading to high mortality. They have an increased fat mass (FM) and decreased lean body mass (LBM). During childhood, GH treatment counteracts the natural course of increasing obesity. Discontinuation of GH treatment at attainment of adult height (AH) might deteriorate their improved clinical condition, whereas continuation might benefit them. OBJECTIVE: To investigate the effects of GH versus placebo on body composition in young adults with PWS who were GH treated for many years during childhood and had attained AH. DESIGN: Two-year, randomized, double-blind, placebo-controlled crossover study with stratification for gender and body mass index in 27 young adults with PWS. SETTING: PWS Reference Center in The Netherlands. INTERVENTION: Crossover intervention with GH (0.67 mg/m2 · d) and placebo, both during 1 year. MAIN OUTCOME MEASURES: Body composition, measured by dual-energy x-ray absorptiometry. RESULTS: During placebo, FM increased (relative change +21.5%; P < .001). Compared with placebo, GH treatment resulted in lower FM (-2.9 kg; P = .004) and higher LBM (+1.5 kg; P = .005), representing relative changes of -17.3% FM and +3.5% LBM. Both limb and trunk FM percentage were lower during GH versus placebo (relative change +17.3% and +15.6%; P < .001 and P = .007, respectively). No GH-related adverse events occurred. CONCLUSIONS: GH-treated young adults with PWS who have attained AH benefit from continuation of GH treatment. FM increases during placebo, whereas GH versus placebo results in lower FM and higher LBM. Thus, GH treatment maintains the improved body composition without safety concerns.

Beneficial Effect of Growth Hormone Treatment on Health-Related Quality of Life in Children with Prader-Willi Syndrome: A Randomized Controlled Trial and Longitudinal Study.

BACKGROUND/AIMS: Growth hormone (GH) treatment is beneficial for children with Prader-Willi syndrome (PWS), but data about health-related quality of life (HRQOL) and effects of GH treatment are scarce. We, therefore, investigated the effects of GH treatment on HRQOL in PWS children. METHODS: In a randomized controlled GH trial including 26 PWS children and during an 11-year longitudinal GH study in 76 children, we annually assessed HRQOL recorded by patients and parents, using a generic questionnaire (DUX25), containing 4 subdomains (Physical, Home, Social, and Emotional) and a PWS-specific questionnaire (DUXPW). RESULTS: At baseline, PWS children rated HRQOL similar to or higher than healthy and obese children. GH-treated children reported an increase in HRQOL in the Physical and Social subdomains and the DUXPW compared to untreated children. Parents reported an increase in the Physical and Emotional subdomains and borderline in the total DUX25 compared to parents of untreated children. During the 11 years of GH treatment, the Physical subdomain continued to improve, according to parents, whereas the Home, Social and Emotional subdomains, the total DUX25, and the DUXPW remained similar, according to children and parents. CONCLUSIONS: PWS children rated HRQOL equally to or better than healthy and obese children. HRQOL increased during GH treatment, in contrast to HRQOL of untreated children. This effect was sustained during long-term GH treatment. PWS children consider themselves quite happy, despite some difficulties related to the syndrome.