P03-30 Growth hormone treatment for two years is safe and effective in adults with Prader-Willi syndrome
ABSTRACT Prader-Willi syndrome (PWS) shares similarities with the growth hormone (GH) deficiency syndrome in regards to reduced lean body mass and increased fat mass and several short-term trials with GH treatment have demonstrated beneficial effects on body composition. The aim of the present study was to evaluate the effects and safety of two years of GH therapy in adults with PWS.
Forty-three adults (24 women) with genetically verified PWS were included. Blood samples, body composition as measured by computed tomography (CT) and dual-energy x-ray absorptiometry (DXA) were performed at baseline and during two years of continued GH treatment.
Thirty-nine patients completed treatment for two years. The GH dosage averaged 0.61 mg/day (range 0.2-1.6). Based upon CT, body composition improved at two years; thigh muscle volume increased 6.7 mL (3.7 to 9.7; P<0.001) whereas abdominal subcutaneous fat volume decreased by 53.3 mL (13.8 to 92.9; P=0.01). By DXA, lean body mass improved 2.8 kg (1.9 to 3.6; P<0.001), whereas fat mass decreased by 3.0 kg (1.1 to 4.8; P=0.003). Lung function as evaluated by peak expiratory flow increased 12% (p<0.001) - indicating improved muscle function. Adverse effects were few. Fifteen out of 39 patients had diabetes (DM; n=4) or impaired glucose tolerance (IGT; n=11) prior to GH treatment. Among the 11 patients with IGT, three reverted to normal glucose tolerance, while three progressed to overt DM at two years of GH treatment.
The known beneficial effects of GH treatment upon body composition in PWS are maintained during two years continuous treatment. With appropriate control, GH is a safe treatment option in adults with PWS.
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ABSTRACT: Prader-Willi syndrome (PWS) is characterized by short stature, muscular hypotonia, cognitive dysfunction, and hyperphagia usually leading to severe obesity. Patients with PWS share similarities with growth hormone deficiency (GHD). Few studies have dealt with growth hormone (GH) treatment in PWS adults. The purpose of the Scandinavian study was to evaluate the effects of GH on body composition, lipid and glucose metabolism, physical performance and safety parameters in adults with PWS. Twenty-five women and 21 men with PWS were randomized to treatment with GH or placebo during 1 year followed by 2 years of open labeled GH treatment. At baseline 1/3 had normal BMI, six patients severe GHD, ten impaired glucose tolerance and seven diabetes. At 1 year insulin-like growth factor I (IGF-I) SDS had increased by 1.51 (P < 0.001) and body composition improved in the GH treated group. Visceral fat decreased by 22.9 ml (P = 0.004), abdominal subcutaneous fat by 70.9 ml (P = 0.003) and thigh fat by 21.3 ml (P = 0.013), whereas thigh muscle increased 6.0 ml (P = 0.005). Lean body mass increased 2.25 kg (P = 0.005), and total fat mass decreased 4.20 kg (P < 0.001). The positive effects on body composition were maintained after 2 years of GH treatment. Peak expiratory flow increased by 12% (P < 0.001) at 2 years of GH treatment. Lipid and glucose metabolism were unchanged, however, three patients developed diabetes at 2 years of GH treatment. In conclusion GH treatment had beneficial effects on the abnormal body composition without serious adverse events making it a logic treatment option in adults with PWS.Endocrine 11/2011; 41(2):191-9. DOI:10.1007/s12020-011-9560-4 · 3.53 Impact Factor
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ABSTRACT: Prader Willi syndrome (PWS) is a genetic disorder (15q11-q13) characterized by short stature, hypogonadism leading to osteoporosis, delayed puberty, central hypocorticism and the most life threatening, excessive appetite which is followed by morbid obesity. Patients with PWS present reduced GH secretion, hypogonadotropic hypogonadism, abnormal appetite control and high pain threshold suggesting hypothalamic-pituitary dysfunction. However, all high resolution imaging studies are normal; due to changes in Chr 15, the hypothalamic function is disrupted. All patients with PWS show severe disturbances in appetite control resulting in hyperphagia and obesity. Peptides involved in hypothalamic appetite control as ghrelin. leptin, NPY/AGRP, POMC, and their cognate receptors, are involved in developmental processes, determine the threshold for signals of body fat below which increases in energy intake and reductions in energy expenditure. In addition, low GH and IGF1 level, central hypothyroidism, delayed puberty and central hypogonadism may impact upon the body composition. Despite the detailed knowledge about obesity mechanisms regulated at hypothalamic level, the pharmacological intervention is limited currently to substitution of proven endocrine deficiencies and GH treatment. The PWS brain seems "wired" for a positive energy balance, and very few pathways can counterbalance this genetic imprintingChoroid Plexus - Pineal Gland Correlations Medical Anthropology - Computed Tomography Studies Intracranial Physiological Calcification 01/2012; 8(1-1):99-105. DOI:10.4183/aeb.2012.99 · 0.21 Impact Factor
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ABSTRACT: Growth hormone (GH) is approved by the US Food and Drug Administration (FDA) for use in pediatric patients with disorders of growth failure or short stature and in adults with growth hormone deficiency (GHD) and HIV/AIDS wasting and cachexia. For pediatric patients, guidelines for the use of GH have been developed by several organizations that have identified specific criteria for initiating GH therapy for each FDA-approved indication. Guidelines for adults have also been developed and include recommendations for transition (adolescent) patients with GHD. These patients are often treated with GH as children but may require continued treatment as young adults to attain full skeletal mineralization and improve cardiovascular risk factors. Adult and pediatric guidelines are supported by efficacy and safety studies, which show that, when started at an early age, GH treatment can increase growth velocity and that GH is safe and well-tolerated. We summarize the guidelines that are available for all FDA-approved indications among pediatric and transition patients. Adherence to these guidelines will help to ensure that patients with disorders of growth failure or short stature receive the necessary therapy to increase linear growth and transition smoothly to healthy adulthood.Pituitary 01/2012; 15(3):301-10. DOI:10.1007/s11102-011-0372-6 · 2.22 Impact Factor