Abstract
Background: Prader-Willi syndrome (PWS) is associated with an inappropriate proportion of fat mass (FM) to non-FM compared to simple obesity. Altered body composition in PWS resembles that seen in subjects with GH deficiency, in which a reduction of lean body mass (LBM) is observed. The low LBM may contribute to the reduced motor skills seen in PWS patients. Aim: The objective of the study was to investigate the effects of GH therapy on exercise capacity and body composition in a group of adult subjects with PWS. Subjects and methods: Twelve PWS adults (7 males and 5 females, aged 26.4±4.4 yr, body mass index 44.3±4.6 kg/m2) participated in the study. Body composition analysis and exercise stress test were carried out throughout the 12 months GH therapy. Body composition was measured by Dual Energy X-ray Absorptiometry. Physical performance was evaluated using treadmill exercise test. Exercise intensity was expressed as metabolic equivalents (MET, 1 MET= 3.5 ml O2 kg−1min−1). Statistical analysis was performed by repeated-measures analysis of variance followed by post-hoc analysis with t test for paired data for comparisons among the different follow ups. Results: Compared to baseline GH therapy increased LBM at 6 (p<0.0001) and 12 months (p<0.005) (45.3±7.7 kg vs 48.6±6.7 kg vs 48.2±7.5 kg). FM% was significantly reduced both after 6 and 12 months (p<0.02) (56.1 ±4.8% vs 53.7±4.2% vs 53.3±4.8%). Attained MET were found to be improved by 16% after 6 months and by 19% after 12 months of GH (p<0.001), while the small further rise between 6 and 12 months was not significant. Conclusions: Our findings seem to support the view that GH therapy has beneficial effects on physical activity and agility as well as on body composition of adult patients with PWS.
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Buiting K, Horsthemke B. Molecular genetic findings in Prader-Willi syndrome. In: Butler MG, Lee PDK, Whitman BY eds. Management of Prader-Willi syndrome, 3rd ed. New York: Springer. 2006, 58–73.
Goldstone AP. Prader-Willi syndrome: advances in genetics, pathophysiology and treatment. Trends Endocrinol Metab 2004, 15: 12–20.
Brambilla P, Bosio L, Manzoni P, Pietrobelli A, Beccaria L, Chiumello G. Peculiar body composition in patients with Prader-Labhart-Willi syndrome. Am J Clin Nutr 1997, 65: 1369–74.
Theodoro MF, Talebizadeh Z, Butler MG. Body composition and fatness patterns in Prader-Willi syndrome: comparison with simple obesity. Obesity (Silver Spring) 2006, 14: 1685–90.
Chedd N, Levine K, Wharton RH. Educational considerations for children with Prader-Willi syndrome. In: Butler MG, Lee PDK, Whitman BY eds. Management of Prader-Willi syndrome, 3rd ed. New York: Springer. 2006, 302–16.
Eiholzer U, Blum WF, Molinari L. Body fat determined by skinfold measurements is elevated despite underweight in infants with Prader-Labhart-Willi syndrome. J Pediatr 1999, 134: 222–5.
Zipf WB. Prader-Willi syndrome: the care and treatment of infants, children, and adults. Adv Pediatr 2004, 51: 409–34.
Allen DB, Carrel AL. Growth hormone therapy for Prader-Willi syndrome: a critical appraisal. J Pediatr Endocrinol Metab 2004, 17: 1297–306.
Burman P, Ritzén EM, Lindgren AC. Endocrine dysfunction in Prader-Willi syndrome: a review with special reference to GH. Endocr Rev 2001, 22: 787–99.
Grugni G, Marzullo P, Ragusa L, et al. Impairment of GH responsiveness to combined GH-releasing hormone and arginine administration in adult patients with Prader-Willi syndrome. Clin Endocrinol (Oxf) 2006, 65: 492–9.
Grugni G, Guzzaloni G, Moro D, Bettio D, De Medici C, Morabito F. Reduced growth hormone (GH) responsiveness to combined GH-releasing hormone and pyridostigmine administration in the Prader-Willi syndrome. Clin Endocrinol 1998, 48: 769–75.
Carrel AL, Myers SE, Whitman BY, Allen DB. Benefits of long-term GH therapy in Prader-Willi syndrome: a 4-year study. J Clin Endocrinol Metab 2002, 87: 1581–5.
Carrel AL, Myers SE, Whitman BY, Allen DB. Growth hormone improves body composition, fat utilization, physical strength and agility in Prader-Willi syndrome: A controlled study. J Pediatr 1999, 134: 215–21.
Myers SE, Whitman BY, Carrel AL, Moerchen V, Bekx MT, Allen DB. Two years of growth hormone therapy in young children with Prader-Willi syndrome; physical and neurodevelopmental benefits. Am J Med Genet Part A 2007, 143: 443–8.
Hoybye C, Hilding A, Jacobson H, Thoren M. Growth hormone treatment improves body composition in adults with Prader-Willi syndrome. Clin Endocrinol (Oxf) 2003, 58: 653–61.
Marzullo P, Marcassa C, Campini R, et al. The impact of growth hormone/insulin-like growth factor-I axis and nocturnal breathing disorders on cardiovascular features of adult patients with Prader-Willi syndrome. J Clin Endocrinol Metab 2005, 90: 5639–46.
Tanner JM, Whitehouse RH, Takaishi M. Standards from birth to maturity for height, weight, height velocity, and weight velocity: British children, 1965 II. Arch Dis Child 1966, 41: 613–35.
Corneli G, Di Somma C, Baldelli R, et al. The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index. Eur J Endocrinol 2005, 153: 257–64.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985, 28: 412–9.
Bonora E, Kiechl S, Willeit J, et al. Prevalence of insulin resistance in metabolic disorders. The Bruneck Study. Diabetes 1998, 47: 1643–9.
McInnis KJ, Bader DS, Pierce GL, Balady GJ. Comparison of cardiopulmonary responses in obese women using ramp versus step treadmill protocols. Am J Cardiol 1999, 83: 289–91.
Fletcher GF, Balady GJ, Amsterdam EA, et al. Exercise standards for testing and training: a statement for healthcare professionals of the American Heart Association. Circulation 2001, 104: 1694–740.
Einfeld SL, Kavanagh SJ, Smith A, Evans EJ, Tonge BJ, Taffe J. Mortality in Prader-Willi syndrome. Am J Ment Retard 2006, 111: 193–8.
Butler MG, Theodoro MF, Bittel DC, Donnelly JE. Energy expenditute and physical activity in Prader-Willi syndrome: comparison with obese subjects. Am J Med Genet 2007, 143: 449–59.
Scheimann AO, Lee PDK, Ellis KJ. Gastrointestinal System, Obesity and Body composition. In: Butler MG, Lee PDK, Whitman BY eds. Management of Prader-Willi syndrome, 3rd ed. New York: Springer. 2006, 153–200.
van Mil EG, Westerterp KR, Gerver WJ, van Marken Lichtenbelt WD, Kester AD, Saris WH. Body composition in Prader-Willi syndrome compared with nonsyndromal obesity: Relationship to physical activity and growth hormone function. J Pediatr 2001, 139: 708–14.
Lindgren AC, Hagenäs L, Müller J, et al. Growth hormone treatment of children with Prader-Willi syndrome affects linear growth and body composition favourably. Acta Paediatr 1998, 87: 28–31.
Carrel AL, Moerchen V, Myers SE, Bekx MT, Whitman BY, Allen DB. Growth hormone improves mobility and body composition in infants and toddlers with Prader-Willi syndrome. J Pediatr 2004, 145: 744–9.
Vogels A, Fryns JP. Age at diagnosis, body mass index and physical morbidity in children and adults with the Prader-Willi syndrome. Genet Couns 2004, 15: 397–404.
Drake WM, Howell SJ, Monson JP, Shalet SM. Optimizing GH therapy in adults and children. Endocr Rev 2001, 22: 425–50.
Haqq AM, Stadler DD, Jackson RH, Rosenfeld RG, Purnell JQ, La Franchi SH. Effects of growth hormone on pulmonary function, sleep quality, behavior, cognition, growth velocity, body composition, and resting energy expenditure in Prader-Willi syndrome. J Clin Endocrinol Metab 2003, 88: 2206–12.
Carrel AL, Myers SE, Whitman BY, Allen DB. Sustained benefits of growth hormone on body composition, fat utilization, physical strength and agility in Prader-Willi syndrome are dose-dependent. J Pediatr Endocrinol Metab 2001, 14: 1097–105.
Marzullo P, Marcassa C, Campini R, et al. Conditional cardiovascular response to growth hormone therapy in adult patients with Prader-Willi syndrome. J Clin Endocrinol Metab 2007, 92: 1364–71.
Carrel A, Lee PDK, Mogul HR. Growth hormone and Prader-Willi syndrome. In: Butler MG, Lee PDK, Whitman BY eds. Management of Prader-Willi syndrome, 3rd ed. New York: Springer. 2006, 201–41.
Chrisoulidou A, Beshyah SA, Rutherford O, et al. Effects of 7 years of growth hormone replacement therapy in hypopituitary adults. J Clin Endocrinol Metab 2000, 85: 3762–9.
Gondoni LA, Liuzzi A, Titon AM, et al. A simple tool to predict exercise capacity of obese patients with ischemic heart disease. Heart 2006, 92: 899–904.
Vismara L, Romei M, Galli M, et al. Clinical implications of gait analysis in the rehabilitation of adult patients with Prader-Willi syndrome: a cross-sectional comparative study (Prader-Willi syndrome vs matched obese patients and healthy subjects). J Neuroeng Rehabil 2007, 4: 14.
Carroll PV, Christ ER, Bengtsson BA, et al. Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. Growth Hormone Research Society Scientific Committee. J Clin Endocrinol Metab 1998, 83: 382–95.
Genth-Zotz S, Zotz R, Geil S, Voigtländer T, Meyer J, Darius H. Recombinant growth hormone therapy in patients with ischemic cardiomyopathy: effects on hemodynamics, left ventricular function, and cardiopulmonary exercise capacity. Circulation 1999, 99: 18–21.
Volterrani M, Desenzani P, Lorusso R, d’Aloia A, Manelli F, Giustina A. Haemodynamic effects of intravenous growth hormone in congestive heart failure. Lancet 1997, 349: 1067–8.
Colao A, Di Somma C, Cuocolo A, et al. The severity of growth hormone deficiency correlates with the severity of cardiac impairment in 100 adult patients with hypopituitarism: an observational, case-control study. J Clin Endocrinol Metab 2004, 89: 5998–6004.
ter Maaten JC, de Boer H, Kamp O, Stuurman L, van der Veen EA. Long-term effects of growth hormone (GH) replacement in men with childhood-onset GH deficiency. J Clin Endocrinol Metab 1999, 84: 2373–80.
Nass R, Huber RM, Klauss V, Müller OA, Schopohl J, Strasburger CJ. Effect of growth hormone (hGH) replacement therapy on physical work capacity and cardiac and pulmonary function in patients with hGH deficiency acquired in adulthood. J Clin Endocrinol Metab 1995, 80: 552–7.
Craig ME, Cowell CT, Larsson P, et al. Growth hormone treatment and adverse events in Prader-Willi syndrome: data from KIGS (the Pfizer international growth database). Clin Endocrinol (Oxf) 2006, 65: 178–85.
Bertella L, Mori I, Grugni G, et al. Quality of life and psychological well-being in GH-treated, adult PWS patients: a longitudinal study. J Intellect Disabil Res 2007, 51: 302–11.
Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature 2006, 444: 875–80.
Patel S, Harmer JA, Loughnan G, Skilton MR, Steinbeck K, Celermajer DS. Characteristics of cardiac and vascular structure and function in Prader-Willi syndrome. Clin Endocrinol (Oxf) 2007, 66: 771–7.
Schrander-Stumpel CTRM, Curfs LMG, Sastrowijoto P, Cassidy SB, Schrander JJP, Fryns J-P. Prader-Willi syndrome: causes of death in an international series of 27 cases. Am J Med Genet A 2004, 124A: 333–8.
Eiholzer U, Whitman B. A comprehensive team approach to the management of patients with Prader-Willi syndrome. J Pediatr Endocrinol Metab 2004, 17: 1153–75.
Ekelund LG, Haskell WL, Johnson JL, Whaley FS, Criqui MH, Sheps DS. Physical fitness as a predictor of cardiovascular mortality in asymptomatic North American men. The Lipid Research Clinics Mortality Follow-up Study. N Engl J Med 1988, 319: 1379–84.
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Gondoni, L.A., Vismara, L., Marzullo, P. et al. Growth hormone therapy improves exercise capacity in adult patients with Prader-Willi syndrome. J Endocrinol Invest 31, 765–772 (2008). https://doi.org/10.1007/BF03349255
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DOI: https://doi.org/10.1007/BF03349255