Skip to main content

Advertisement

SpringerLink
Log in

Growth hormone/insulin-like growth factor-I axis in obstructive sleep apnea syndrome: An update

  • Short Review
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Obstructive sleep apnea syndrome (OSAS) is a serious, prevalent condition that has significant mortality and morbidity when untreated. It is strongly associated with obesity and is characterized by changes in the serum levels or secretory patterns of several hormones. In particular, obese patients with OSAS show a peculiar reduction of both spontaneous and stimulated GH secretion coupled with reduced IGF-I concentrations and impaired peripheral sensitivity to GH. These endocrine abnormalities are more marked than those observed in non-apneic obese subjects, and are likely to be due to the effects of hypoxia and sleep fragmentation on hormone secretory pattern. The GH/IGF-I axis activity disruption can be responsible, at least in part, for metabolic alterations, which are common in OSAS and increase the risk of cardiovascular events as well as mortality. Effective assessment and management of OSAS may correct endocrine changes, improve quality of life, and prevent associated morbidity or death.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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. American Thoracic Society/American Sleep Disorders Association. Statement on health outcomes research in sleep apnea. Am J Respir Crit Care Med 1998, 157: 335–41.

    Article  Google Scholar 

  2. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep 1999, 22: 667–89.

    Google Scholar 

  3. Iber C, Ancoli-Israel S, Chesson A, Quan S; the American Academy of Sleep Medicine. The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications. 1st ed. Westchester, IL: American Academy of Sleep Medicine, 2007.

  4. Guilleminault C, van den Hoed J, Mitler M. Clinical features and evaluation of obstructive sleep apnea. In Principles and Practice of Sleep Medicine. Kryger MH, Roth T, Dement WC eds. Philadelphia: WB Saunders Co. 1994, 667–77.

  5. Bixler EO, Vgontzas AN, Ten Have T, Tyson K, Kales A. Effects of age and sleep apnea in men. I. Prevalence and severity. Am J Respir Crit Care Med 1998, 157: 144–8.

    Article  PubMed  CAS  Google Scholar 

  6. Bixler EO, Vgontzas AN, Lin HM, et al. Prevalence of sleep-disordered breathing in women: effects of gender. Am J Respir Crit Care Med 2001, 163: 608–13.

    Article  PubMed  CAS  Google Scholar 

  7. Kales A, Vela-Bueno A, Kales JD. Sleep disorders: sleep apnea and narcolepsy. Ann Intern Med 1987, 106: 434–43.

    Article  PubMed  CAS  Google Scholar 

  8. Vgontzas AN, Papanicolaou DA, Bixler EO, et al. Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Metab 2000, 85: 1151–8.

    Article  PubMed  CAS  Google Scholar 

  9. Svatikova A, Wolk R, Gami AS, Pohanka M, Somers VK. Interactions between obstructive sleep apnea and the metabolic syndrome. Curr Diab Rep 2005, 5: 53–8.

    Article  PubMed  Google Scholar 

  10. Zamarron C, García Paz V, Riveiro A. Obstructive sleep apnea syndrome is a systemic disease. Current evidence. Eur J Intern Med 2008, 19: 390–8.

    Article  Google Scholar 

  11. Pillar G, Shehadeh N. Abdominal fat and sleep apnea: the chicken or the egg? Diabetes Care 2008, 31: S303–9.

    Article  PubMed  Google Scholar 

  12. Chesson AL Jr, Berry RB, Pack A; American Academy of Sleep Medicine; American Thoracic Society; American College of Chest Physicians. Practice parameters for the use of portable monitoring devices in the investigation of suspected obstructive sleep apnea in adults. Sleep 2003, 26: 907–13.

    PubMed  Google Scholar 

  13. Mattei A, Tabbia G, Baldi S. Diagnosis of sleep apnea. Minerva Med 2004, 95: 213–31.

    PubMed  CAS  Google Scholar 

  14. Collop NA, Anderson WM, Boehlecke B, et al; Portable Monitoring Task Force of the American Academy of Sleep Medicine. Clinical guidelines for the use of unattended portable monitors in the diagnosis of obstructive sleep apnea in adult patients. Portable Monitoring Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med 2007, 3: 737–47.

    PubMed  Google Scholar 

  15. Littner M. Polysomnography in the diagnosis of the obstructive sleep apnea-hypopnea syndrome: where do we draw the line? Chest 2000, 118:286–8.

    Article  PubMed  CAS  Google Scholar 

  16. Gami AS, Caples SM, Somers VK. Obesity and obstructive sleep apnea. Endocrinol Metab Clin North Am 2003, 32: 869–94.

    Article  PubMed  Google Scholar 

  17. Bloch KE. Alternatives to CPAP in the treatment of the obstructive sleep apnea syndrome. Swiss Med Wkly 2006, 136: 261–7.

    PubMed  Google Scholar 

  18. Phillips B. Upper airway surgery does not have a major role in the treatment of sleep apnea. J Clin Sleep Med 2005, 1: 241–5.

    PubMed  Google Scholar 

  19. Powell NB. Contemporary surgery for obstructive sleep apnea syndrome. Clin Exp Otorhinolaryngol 2009, 2: 107–14.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 2004, 292: 1724–37.

    Article  PubMed  CAS  Google Scholar 

  21. Blum WF, Albertsson-Wikland K, Rosberg S, Ranke MB. Serun levels of insulin like growth factor I (IGF-I) and IGF binding protein 3 reflects spontaneous growth hormone secretion. J Clin Endocrinol Metab 1993, 76: 1610–6.

    PubMed  CAS  Google Scholar 

  22. Bernstein D, Kasper JR, Rosenfeld RG, Hintz RL. Decreased serum insulin like growth factor-I associated with growth failure in newborn lambs with experimental cyanotic heart disease. J Clin Invest 1992, 89: 1128–32.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  23. Xu NY, Chen XQ, Du JZ, Wang TY, Duan C. Intermittent hypoxia causes a suppressed pituitary growth hormone through somatostatin. Neuro Endocrinol Lett 2004, 25: 361–7.

    PubMed  CAS  Google Scholar 

  24. Zhang YS, Du JZ. The response of growth hormone and prolactin of rats to hypoxia. Neurosci Lett 2000, 279: 137–40.

    Article  PubMed  CAS  Google Scholar 

  25. Polo O, Berthon-Jones M, Douglas NJ, Sullivan CE. Management of obstructive sleep apnoea/hypopnoea syndrome. Lancet 1994, 344: 656–60.

    Article  PubMed  CAS  Google Scholar 

  26. Ekstedt M, Akerstedt T, Söderström M. Microarousals during sleep are associated with increased levels of lipids, cortisol, and blood pressure. Psychosom Med 2004, 66: 925–31.

    Article  PubMed  CAS  Google Scholar 

  27. Semple PD, Beastall GH, Watson WS, Hume R. Hypothalamic-pituitary dysfunction in respiratory hypoxia. Thorax 1981, 36: 605–9.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Pastuszko A, Wilson DF, Ericinsk M. Neurotransmitter metabolism in rat brain synaptosomes: effect of anoxia and pH. J Neurochem 1982, 38: 1657–67.

    Article  PubMed  CAS  Google Scholar 

  29. Raff H, Shinsako J, Keil LC, Dallman MF. Vasopressin, ACTH, and corticosteroids during hypercapnia and graded hypoxia in dogs. Am J Physiol 1983, 244: E453–8.

    PubMed  CAS  Google Scholar 

  30. Young T, Peppard PE, Taheri S. Excess weight and sleep-disordered breathing. J Appl Physiol 2005, 99: 1592–9.

    Article  PubMed  Google Scholar 

  31. Horner RL, Mohiaddin RH, Lowell DG. Sites and sizes of fat deposits around the pharynx in obese patients with obstructive sleep apnea and weight matched controls. Eur Respir J 1989, 2: 613–22.

    PubMed  CAS  Google Scholar 

  32. Rubinstein I, Hoffstein V, Bradley TD. Lung volume-related changes in the pharyngeal area of obese females with and without obstructive sleep apnoea. Eur Respir J 1989, 2: 344–51.

    PubMed  CAS  Google Scholar 

  33. Strobel RJ, Rosen RC. Obesity and weight loss in obstructive sleep apnoea: a critical review. Sleep 1996, 19: 104–15.

    PubMed  CAS  Google Scholar 

  34. Lavie P, Herer P, Hoffstein V. Obstructive sleep apnoea syndrome as a risk factor for hypertension: population study. BMJ 2000, 320: 479–82.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  35. Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000, 342: 1378–84.

    Article  PubMed  CAS  Google Scholar 

  36. Glass AR, Burman KD, Dahms WT, Boehm TM. Endocrine function in human obesity. Metabolism 1981, 130: 89–104.

    Article  Google Scholar 

  37. Veldhuis JD, Iranmanesh A, Ho KK, Waters MJ, Johnson ML, Lizarralde G. Dual defects in pulsatile growth hormone secretion and clearances subserve the hyposomatotropism of obesity in man. J Clin Endocrinol Metab 1991, 72: 51–9.

    Article  PubMed  CAS  Google Scholar 

  38. Scacchi M, Pincelli AI, Cavagnini F. Growth hormone in obesity. Int J Obes Relat Metab Disord 1999, 23: 260–71.

    Article  PubMed  CAS  Google Scholar 

  39. Maccario M, Valetto MR, Savio P, et al. Maximal secretory capacity of somatotrope cells in obesity: comparison with GH deficiency. Int J Obes Relat Metab Disord 1997, 21: 27–32.

    Article  PubMed  CAS  Google Scholar 

  40. Cordido F, Casanueva FF, Dieguez C. Cholinergic receptor activation by pyridostigmine restores growth hormone (GH) responsiveness to GH-releasing hormone administration in obese subjects: evidence for hypothalamic somatostatinergic participation in the blunted GH release of obesity. J Clin Endocrinol Metab 1989, 68: 290–3.

    Article  PubMed  CAS  Google Scholar 

  41. Maccario M, Grottoli S, Procopio M, et al. The GH/IGF-I axis in obesity: influence of neuroendocrine and metabolic factors. Int J Obes Relat Metab Disord 2000, 24 (Suppl 2): S96–9.

    Article  PubMed  CAS  Google Scholar 

  42. Alvarez CV, Mallo F, Burguera B, Cacicedo L, Dieguez C, Casanueva FF. Evidence for a direct pituitary inhibition by free fatty acid of in vivo growth hormone responses to growth hormone-releasing hormone in the rat. Neuroendocrinology 1991, 53: 185–9.

    Article  PubMed  CAS  Google Scholar 

  43. Frystyk J, Vestbo E, Skjaerbaek C, Mogensen CE, Orskov H. Free insulin-like growth factor in human obesity. Metabolism 1995, 44 (Suppl 4): 37–44.

    Article  PubMed  CAS  Google Scholar 

  44. Cordido F, Fernandez T, Martinez T, et al. Effect of acute pharmacological reduction of plasma free fatty acids on GHRH-induced GH secretion in obese adults with and without hypopituitarism. J Clin Endocrinol Metab 1998, 83: 4350–4.

    PubMed  CAS  Google Scholar 

  45. Cordido F, Alvarez-Castro P, Isidro ML, Casanueva FF, Dieguez C. Comparison between insulin tolerance test, growth hormone (GH)- releasing hormone (GHRH), GHRH plus acipimox, and GHRH plus GH-releasing peptide-6 for the diagnosis of adult GH deficiency in normal subjects, obese and hypopituitary patients. Eur J Endocrinol 2003, 149: 117–22.

    Article  PubMed  CAS  Google Scholar 

  46. Maccario M, Tassone F, Grottoli S, Rossetto R, Gauna C, Ghigo E. Neuroendocrine and metabolic determinants of the adaptation of GH/IGF-I axis to obesity. Ann Endocrinol (Paris) 2002, 63: 140–4.

    CAS  Google Scholar 

  47. Alvarez-Castro P, Isidro ML, Garcia-Buela J, et al. Marked GH secretion after ghrelin alone or combined with GH-releasing hormone (GHRH) in obese patients. Clin Endocrinol (Oxf) 2004, 61: 250–5.

    Article  CAS  Google Scholar 

  48. Maccario M, Ramunni J, Oleandri SE, et al. Relationships between IGF-I and age, gender, body mass, fat distribution, metabolic and hormonal variables in obese patients. Int J Obes Relat Metab Disord 1999, 23: 612–8.

    Article  PubMed  CAS  Google Scholar 

  49. Maccario M, Tassone F, Gauna C, et al. Effects of short-term administration of low-dose rhGH on IGF-I levels in obesity and Cushing’s syndrome: indirect evaluation of sensitivity to GH. Eur J Endocrinol 2001, 144: 251–6.

    Article  PubMed  CAS  Google Scholar 

  50. Mekala KC, Tritos NA. Effects of recombinant human growth hormone therapy in obesity in adults: a meta analysis. J Clin Endocrinol Metab 2009, 94: 130–7.

    Article  PubMed  CAS  Google Scholar 

  51. Saini J, Krieger J, Brandenberger G, Wittersheim G, Follenius M. Continuous positive airway pressure treatment effects on growth hormone, insulin, and glucose profiles in obstructive sleep apnea patients. Horm Metab Res 1993, 25: 375–81.

    Article  PubMed  CAS  Google Scholar 

  52. Cooper BG, White JE, Ashworth LA, Alberti KG, Gibson GJ. Hormonal and metabolic profiles in subjects with obstructive sleep apnea syndrome and the acute effects of nasal continuous positive airway pressure (CPAP) treatment. Sleep 1995, 18: 172–9.

    PubMed  CAS  Google Scholar 

  53. Grunstein RR, Handelsman DJ, Lawrence SJ, Blackwell C, Caterson ID, Sullivan CE. Neuroendocrine dysfunction in sleep apnea: reversal by continuous positive airways pressure therapy. J Clin Endocrinol Metab 1989, 68: 352–8.

    Article  PubMed  CAS  Google Scholar 

  54. Ursavas A, Karadag M, Ilcol YO, et al. Low level of IGF-1 in obesity may be related to obstructive sleep apnea syndrome. Lung 2007, 185: 309–14.

    Article  PubMed  CAS  Google Scholar 

  55. McArdle N, Hillman D, Beilin L, Watts G. Metabolic risk factors for vascular disease in obstructive sleep apnea: a matched controlled study. Am J Respir Crit Care Med 2007, 175: 190–5.

    Article  PubMed  CAS  Google Scholar 

  56. Gianotti L, Pivetti S, Lanfranco F, et al. Concomitant impairment of growth hormone secretion and peripheral sensitivity in obese patients with obstructive sleep apnea syndrome. J Clin Endocrinol Metab 2002, 87: 5052–7.

    Article  PubMed  CAS  Google Scholar 

  57. Ghigo E, Aimaretti G, Arvat E, Camanni F. Growth hormone-releasing hormone combined with arginine or growth hormone secretagogues for the diagnosis of growth hormone deficiency in adults. Endocrine 2001, 15: 29–38.

    Article  PubMed  CAS  Google Scholar 

  58. Van Cauter E, Latta F, Nedeltcheva A. Reciprocal interactions between the GH axis and sleep. Growth Horm IGF Res 2004, 14 (Suppl A): S10–7.

    Google Scholar 

  59. Parker DC, Sassin JF, Mace JW, Gotlin RW, Rossman LG. Human growth hormone release during sleep: electroencephalographic correlation. J Clin Endocrinol Metab 1969, 29: 871–4.

    Article  PubMed  CAS  Google Scholar 

  60. Ocampo-Lim B, Guo W, DeMott Friberg R, Barkan AL, Jaffe CA. Nocturnal growth hormone (GH) secretion is eliminated by infusion of GH-releasing hormone antagonist. J Clin Endocrinol Metab 1996, 81: 4396–9.

    PubMed  CAS  Google Scholar 

  61. Kerkhofs M, Van Cauter E, Van Onderbergen A, Caufriez A, Thorner MO, Copinschi G. Sleep-promoting effects of growth hormone-releasing hormone in normal men. Am J Physiol 1993, 264: E594–8.

    PubMed  CAS  Google Scholar 

  62. Kamel NS, Gammack JK. Insomnia in the elderly: cause, approach, and treatment. Am J Med 2006, 119: 463–9.

    Article  PubMed  Google Scholar 

  63. Bradley TD, Phillipson EA. Pathogenesis and pathophysiology of obstructive sleep apnea syndrome. Med Clin N Am 1985, 69: 1169–85.

    PubMed  CAS  Google Scholar 

  64. Krieger J. Sleep apnea syndrome in adults. Bull Eur Physiopathol Respir 1986, 22: 147–89.

    PubMed  CAS  Google Scholar 

  65. Melmed S. Insulin suppresses growth hormone secretion by rat pituitary cells. J Clin Invest 1984, 73: 1425–33.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  66. Houston B, O’Neill IE. Insulin and growth hormone act synergisticallyto stimulate insulin-like growth factor-I production by cultured chicken hepatocytes. J Endocrinol 1991, 128: 389–93.

    Article  PubMed  CAS  Google Scholar 

  67. Tassone F, Lanfranco F, Gianotti L, et al. Obstructive sleep apnoea syndrome impairs insulin sensitivity independently of anthropometric variables. Clin Endocrinol 2003, 59: 374–9.

    Article  Google Scholar 

  68. Tasali E, Van Cauter E, Ehrmann DA. Polycystic ovary syndrome and obstructive sleep apnea. Sleep Med Clin 2008, 3: 37–46.

    Article  PubMed Central  PubMed  Google Scholar 

  69. Tucci M, Nygard K, Tanswell BV, Farber HW, Hill DJ, Han VK. Modulation of insulin-like growth factor (IGF) and IGF binding protein biosynthesis by hypoxia in cultured vascular endothelial cells. Endocrinology 1998, 157: 13–24.

    Article  CAS  Google Scholar 

  70. Broglio F, Fubini A, Morello M, et al. Activity of GH/IGF-I axis in patients with dilated cardiomyopathy. Clin Endocrinol (Oxf) 1999, 50: 417–30.

    Article  CAS  Google Scholar 

  71. Lindberg E, Berne C, Elmasry A, Hedner J, Janson C. CPAP treatment of a population-based sample — what are the benefits and the treatment compliance? Sleep Med 2006, 7: 553–60.

    Article  PubMed  Google Scholar 

  72. Sandhu MS, Heald AH, Gibson JM, Cruickshank JK, Dunger DB, Wareham NJ. Circulating concentrations of insulin-like growth factor-1 and development of glucose intolerance: a prospective observational study. Lancet 2002, 359: 1740–5.

    Article  PubMed  CAS  Google Scholar 

  73. Laughlin GA, Barrett Connor E, Criqui MH, Kritz-Silverstein D. The prospective association of serum insulin-like growth factor I (IGF-I) and IGF-I binding protein-1 levels with all-cause and cardiovascular disease mortality in older adults: The Rancho Bernardo Study. J Clin Endocrinol Metab 2004, 89: 114–20.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Endocrinology, Diabetology and Metabolism, Department of Internal Medicine, University of Turin, Corso Dogliotti 14, 10126, Torino, Italy

    F. Lanfranco MD, PhD, G. Motta, M. A. Minetto, E. Ghigo & M. Maccario

Authors
  1. F. Lanfranco MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Motta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. A. Minetto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Ghigo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Maccario
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F. Lanfranco MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lanfranco, F., Motta, G., Minetto, M.A. et al. Growth hormone/insulin-like growth factor-I axis in obstructive sleep apnea syndrome: An update. J Endocrinol Invest 33, 192–196 (2010). https://doi.org/10.1007/BF03346580

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03346580

Keywords

Search

Navigation