Growth Hormone Therapy in Adults with Prader-Willi Syndrome

Abstract

Prader-Willi syndrome (PWS) is a complex multisystem genetic disorder characterized by hypothalamic-pituitary dysfunction. The main clinical features consist of neonatal hypotonia, distinctive facial features, delayed overall development with mental deficiency, behavioral abnormalities, poor growth in infancy followed by overeating with severe obesity, short stature, and hypogonadism. Many features of PWS indicate a deficiency in growth hormone (GH) production, including low growth velocity despite obesity, reduced lean body mass, low insulin-like growth factor-I (IGF-I) levels, and low insulin levels. These findings provide a rationale for GH therapy in PWS. The Food and Drug Administration approved treatment in children genetically confirmed with PWS in 2000 without prior laboratory determination of GH deficiency (GHD). GH treatment is now commonly prescribed in infancy and childhood to increase stature in PWS cases, but also increases muscle and decrease fat, thereby lowering risk factors for diabetes and cardiopulmonary problems. Increased alertness, physical activity, and self-esteem in older children are potential effects of GH treatment, which should improve the quality of life in adulthood. In addition, Lindgren and Lindberg documented that GH treatment in children with PWS appears to normalize them to an adult height with improvement in body composition, an important outcome for individuals with this disorder. Early GH therapy during the first two years may improve neurodevelopment, increase muscle mass, and reduce obesity in PWS infants. It is possible that rhGH therapy could have beneficial effects in adults with PWS, similar to those in adults with GHD of non-syndromic cause. However, there is also concern about potential risks of this therapy, as rhGH has anti-insulin effects and might impair respiratory function in children with underlying sleep apnea, which is frequently present in patients with PWS. However, there is a paucity of data on the use of GH in adults with PWS; existing studies have small in scope, suggesting that the findings of individual studies may be difficult to extrapolate to the population of adult patients with PWS at large. Here, the previous studies about efficacy and safety of rhGH therapy in Review Article