P03-30 Growth hormone treatment for two years is safe and effective in adults with Prader-Willi syndrome

Centre for Rare Diseases, Department of Paediatrics, Aarhus University Hospital Skejby, DK-8200 Aarhus N, Denmark.
Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society (Impact Factor: 1.41). 06/2011; 21(4):185-90. DOI: 10.1016/j.ghir.2011.05.002
Source: PubMed


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.
    No preview · Article · Nov 2011 · Endocrine
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    ABSTRACT: Prader-Willi syndrome (PWS) is associated with GH deficiency, deleterious changes in body composition and function. As the effects of recombinant human GH (rhGH) in PWS adults have not been well established, we sought to conduct a meta-analysis of pertinent studies. Meta-analysis of studies examining the effects of rhGH therapy in PWS adults. One hundred and thirty four PWS adults (75 men, 59 women). Literature searches, including publications (PubMed, EMBASE and the Cochrane Register), and abstracts presented at meetings through July 2011 describing studies of rhGH therapy in PWS adults; 8/1194 articles, describing unique cohorts, were included. Two authors independently extracted data and examined study quality. rhGH therapy for 12 months led to [weighted mean difference (95% CI)] decreased body fat [-2·91% (-3·90, -1·91)], visceral [-32·97 cm(2) (-55·67, -10·26)] and subcutaneous adiposity [-55·24 cm(2) (-89·05, -21·44)], and increased lean body mass (LBM) [2·41 Kg (1·32, 3·49)]. Similar changes in body fat [-2·89% (-4·69, -1·07)] and LBM [2·82 Kg (1·31, 4·33)] were found in longer studies. There were no changes in body mass index (BMI) or lipids. There was a small increase in fasting glucose [0·27 mmol/l (0·05, 0·49)] and trends towards higher fasting insulin [20·24 pmol/l (-0·55, 41·02)] and insulin resistance [HOMA: 0·60 (-0·04, 1·24)] after rhGH therapy for 12 months. In PWS adults, rhGH therapy led to decreased body adiposity and increased LBM without changes in BMI or lipids. There was a small increase in fasting glucose and trends towards higher insulin and insulin resistance.
    No preview · Article · Nov 2011 · Clinical Endocrinology
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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 imprinting
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