Skip to main content
SpringerLink
Log in

Growth hormone therapy improves exercise capacity in adult patients with Prader-Willi syndrome

  • Original Articles
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. 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.

    Chapter  Google Scholar 

  2. Goldstone AP. Prader-Willi syndrome: advances in genetics, pathophysiology and treatment. Trends Endocrinol Metab 2004, 15: 12–20.

    Article  PubMed  CAS  Google Scholar 

  3. 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.

    PubMed  CAS  Google Scholar 

  4. 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.

    Article  Google Scholar 

  5. 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.

    Chapter  Google Scholar 

  6. 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.

    Article  PubMed  CAS  Google Scholar 

  7. Zipf WB. Prader-Willi syndrome: the care and treatment of infants, children, and adults. Adv Pediatr 2004, 51: 409–34.

    PubMed  Google Scholar 

  8. Allen DB, Carrel AL. Growth hormone therapy for Prader-Willi syndrome: a critical appraisal. J Pediatr Endocrinol Metab 2004, 17: 1297–306.

    PubMed  CAS  Google Scholar 

  9. 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.

    Article  PubMed  CAS  Google Scholar 

  10. 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.

    Article  CAS  Google Scholar 

  11. 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.

    Article  CAS  Google Scholar 

  12. 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.

    Article  PubMed  CAS  Google Scholar 

  13. 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.

    Article  PubMed  CAS  Google Scholar 

  14. 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.

    Article  PubMed  CAS  Google Scholar 

  15. 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.

    Article  CAS  Google Scholar 

  16. 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.

    Article  PubMed  CAS  Google Scholar 

  17. 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.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  18. 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.

    Article  PubMed  CAS  Google Scholar 

  19. 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.

    Article  PubMed  CAS  Google Scholar 

  20. Bonora E, Kiechl S, Willeit J, et al. Prevalence of insulin resistance in metabolic disorders. The Bruneck Study. Diabetes 1998, 47: 1643–9.

    Article  PubMed  CAS  Google Scholar 

  21. 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.

    Article  PubMed  CAS  Google Scholar 

  22. 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.

    Article  PubMed  CAS  Google Scholar 

  23. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  24. 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.

    Article  PubMed  Google Scholar 

  25. 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.

    Chapter  Google Scholar 

  26. 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.

    Article  PubMed  Google Scholar 

  27. 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.

    Article  PubMed  CAS  Google Scholar 

  28. 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.

    Article  PubMed  CAS  Google Scholar 

  29. 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.

    PubMed  CAS  Google Scholar 

  30. Drake WM, Howell SJ, Monson JP, Shalet SM. Optimizing GH therapy in adults and children. Endocr Rev 2001, 22: 425–50.

    Article  PubMed  CAS  Google Scholar 

  31. 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.

    Article  PubMed  CAS  Google Scholar 

  32. 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.

    PubMed  CAS  Google Scholar 

  33. 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.

    Article  PubMed  CAS  Google Scholar 

  34. 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.

    Chapter  Google Scholar 

  35. 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.

    PubMed  CAS  Google Scholar 

  36. 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.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  37. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  38. 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.

    Article  PubMed  CAS  Google Scholar 

  39. 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.

    Article  PubMed  CAS  Google Scholar 

  40. 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.

    Article  PubMed  CAS  Google Scholar 

  41. 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.

    Article  PubMed  CAS  Google Scholar 

  42. 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.

    PubMed  Google Scholar 

  43. 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.

    PubMed  CAS  Google Scholar 

  44. 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.

    Article  CAS  Google Scholar 

  45. 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.

    Article  PubMed  CAS  Google Scholar 

  46. Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature 2006, 444: 875–80.

    Article  PubMed  CAS  Google Scholar 

  47. 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.

    Article  Google Scholar 

  48. 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.

    Article  PubMed  Google Scholar 

  49. 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.

    Article  PubMed  CAS  Google Scholar 

  50. 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.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cardiac Rehabilitation, S. Giuseppe Hospital, Research Institute, Istituto Auxologico Italiano, Verbania, Italy

    L. A. Gondoni

  2. Division of Orthopaedic Rehabilitation, S. Giuseppe Hospital, Research Institute, Istituto Auxologico Italiano, Verbania, Italy

    L. Vismara

  3. Division of General Medicine, S. Giuseppe Hospital, Research Institute, Istituto Auxologico Italiano, Verbania, Italy

    P. Marzullo & A. Liuzzi

  4. Department of Internal Medicine, University of Padua, Padua, Italy

    R. Vettor

  5. Division of Auxology, S. Giuseppe Hospital, Research Institute, Istituto Auxologico Italiano, Verbania, Italy

    G. Grugni MD

Authors
  1. L. A. Gondoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. Vismara
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Marzullo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Vettor
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Liuzzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G. Grugni MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. Grugni MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03349255

Key-words

Search

Navigation