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

Abstract

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/m 2 /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.

Three years of growth hormone treatment in young adults with Prader‐Willi Syndrome previously treated with growth hormone in childhood: Effects on glucose homeostasis and metabolic syndrome

“…We previously showed that continuation of GH in early adulthood is able to maintain the improved body composition. 12 It is, therefore, likely that our results are particularly due to the more healthy condition of our study population and may not be applicable to patients with PWS who are obese. However, two studies investigating GH treatment for a maximum of 2 years in GH-naïve adults with PWS included patients with a mean BMI of 28.9 and 33.7 kg/m 2 .…”

“…34 In our placebo-controlled GH study, none developed MS during 1 year of GH treatment, while one developed MS during placebo. 23 As continuation of GH prevents deterioration of body composition, it may thereby contribute to prevention of MS. 11,12 Our study group had a normal median BMI of 24.5 kg/m 2 , being 0.9 SDS, and a relatively healthy body composition compared to young adults with a classical PWS phenotype. 12,35,36 We believe that this is the result of GH treatment during childhood together with multidisciplinary care from a young age onwards.…”

“…However, studies have shown that GH treatment is also beneficial for adults with PWS, as discontinuation leads to a deterioration of body composition, while continuation maintains the improved body composition acquired during childhood. 11,12 Due to their abnormal body composition, adults with PWS are predisposed to develop impaired glucose tolerance (IGT) and diabetes mellitus type 2 (DMT2). 13 In patients developing DMT2, reported mean age at onset was 20 years.…”

<p>Dietary Management for Adolescents with Prader–Willi Syndrome</p>

“…6,7 It also can help contribute to improved weight control by improving muscle strength and motor development, thus increasing the ability of individuals with PWS to participate in physical exercise. 8 Adolescents and young adults with PWS have to discontinue growth hormone treatment after completion of linear growth, unless they meet criteria for adult growth hormone deficiency. 9 However, there is evidence that continuation of growth hormone therapy after cessation of linear growth does continue to have benefits in terms of body composition and metabolism, and that stopping growth hormone treatment in adolescents results in deterioration in body composition.…”

“…The prevalence of obesity in individuals with PWS varies by age groups, although it has been shown to have a prevalence of 40% in children and adolescents. 8 As individuals with PWS enter adulthood, the prevalence of obesity increases to 82% -98%, depending on the study group. 13 It is well accepted that once excessive weight gain and hyperphagia begin, caloric intake must be significantly restricted to prevent obesity.…”