Skip to main content
SpringerLink
Log in

Mortality and Morbidity in Acromegaly: Impact of Disease Control

  • Chapter
  • First Online:
Book cover Growth Hormone Related Diseases and Therapy

Part of the book series: Contemporary Endocrinology ((COE))

  • 1031 Accesses

Abstract

The excess production of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in patients with acromegaly is associated with a range of complications which have important effects on quality of life and which lead to reduced life expectancy. The increased mortality of the disorder has been recognized in 18 studies, totaling 4,806 individuals with acromegaly and including 1,116 deaths during follow-up, with meta-analyses indicating a standardized mortality estimate of 1.7 (95% CI 1.5–2). Univariate and multivariate analyses within the individual studies have identified the presence of hypertension, diabetes, and cardiac disease as important predictors of survival, as well as estimated duration from onset of the condition to date of effective treatment. However, the most important impact on survival comes from reduction of circulating GH and IGF-I concentrations, with serum GH measured by radioimmunoassay of <2.5 μg/L and a serum IGF-I measurement within the normal range for age providing mortality estimates indistinguishable from the general population. The major comorbidities of acromegaly, including cardiovascular disease, stroke, diabetes, hypertension, arthropathy, and sleep apnea syndrome, also benefit from biochemical remission following treatment, and management of these complications of the disorder appears to be important in maintaining quality of life as well as assisting with reduction in mortality.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Melmed S, Colao A, Barkan A, et al. Guidelines for acromegaly management: an update. J Clin Endocrinol Metab. 2009;94:1509–17.

    Article  PubMed  CAS  Google Scholar 

  2. Strasburger CJ. Consensus statement. Biochemical assessment and long-term monitoring in patients with acromegaly: statement from a joint consensus conference of the Growth Hormone Research Society and The Pituitary Society. J Clin Endocrinol Metab. 2004;89:3099–102.

    Article  Google Scholar 

  3. Holdaway IM, Rajasoorya C. Epidemiology of acromegaly. Pituitary. 1999;2:29–41.

    Article  PubMed  CAS  Google Scholar 

  4. Holdaway IM, Rajasoorya RC, Gamble GD. Factors influencing mortality in acromegaly. J Clin Endocrinol Metab. 2004;89:667–74.

    Article  PubMed  CAS  Google Scholar 

  5. Clayton RN. Cardiovascular function in acromegaly. Endocr Rev. 2003;24:272–7.

    Article  PubMed  CAS  Google Scholar 

  6. Colao A, Ferone D, Marzullo P, et al. Systemic complications of acromegaly:epidemiology, pathogenesis, and management. Endocr Rev. 2004;25:102–52.

    Article  PubMed  CAS  Google Scholar 

  7. Paisley AN, Izzard AS, Gemmell I, et al. Small vessel remodelling and impaired endothelial-dependent dilatation in subcutaneous resistance arteries from patients with acromegaly. J Clin Endocrinol Metab. 2009;94:1111–7.

    Article  PubMed  CAS  Google Scholar 

  8. Schiavon F, Maffei P, Martini C, et al. Morphologic study of microcirculation in acromegaly by capillaroscopy. J Clin Endocrinol Metab. 1999;84:3151–5.

    Article  PubMed  CAS  Google Scholar 

  9. Nikkila EA, Pelkonen R. Serum lipids in acromegaly. Metabolism. 1975;24:829–38.

    Article  PubMed  CAS  Google Scholar 

  10. Nabarro JD. Acromegaly. Clin Endocrinol. 1987;26:481–512.

    Article  CAS  Google Scholar 

  11. Holdaway IM, Rajasoorya CR, Gamble GD, et al. Long-term treatment outcome in acromegaly. Growth Horm IGF Res. 2003;13:185–92.

    Article  PubMed  CAS  Google Scholar 

  12. Gouya H, Vignaux O, Le Roux P, et al. Rapidly reversible myocardial edema in patients with acromegaly: assessment with ultrafast T2 mapping in a single-breath-hold MRI sequence. Am J Roentgenol. 2008;190:1576–82.

    Article  Google Scholar 

  13. Pivonello P, Galderisi M, Auriemma RS, et al. Treatment with growth hormone receptor antagonist in acromegaly: effect on cardiac structure and function. J Clin Endocrinol Metab. 2007;92:476–82.

    Article  PubMed  CAS  Google Scholar 

  14. Bogazzi F, Battolla L, Spinelli C, et al. Risk factors for development of coronary heart disease in patients with acromegaly: a 5-year prospective study. J Clin Endocrinol Metab. 2007;92:4271–7.

    Article  PubMed  CAS  Google Scholar 

  15. Cannavo S, Almoto B, Cavalli G, et al. Acromegaly and coronary disease: an integrated evaluation of conventional coronary risk factors and coronary calcifications detected by computed tomography. J Clin Endocrinol Metab. 2006;91:3766–72.

    Article  PubMed  CAS  Google Scholar 

  16. Sacca L, Cittadini A, Fazio S. Growth hormone and the heart. Endocr Rev. 1994;15:555–73.

    PubMed  CAS  Google Scholar 

  17. Pereira AM, Van Thiel SW, Lindner JR, et al. Increased prevalence of regurgitant valvular heart disease in acromegaly. J Clin Endocrinol Metab. 2004;89:71–5.

    Article  PubMed  CAS  Google Scholar 

  18. Van der Klaauw AA, Bax JJ, Roelfsema F, et al. Uncontrolled acromegaly is associated with progressive mitral valvular regurgitation. Growth Horm IGF Res. 2006;16:101–7.

    Article  PubMed  Google Scholar 

  19. Colao A, Marek J, Goth MI, et al. No greater incidence or worsening of cardiac valve regurgitation with somatostatin analog treatment of acromegaly. J Clin Endocrinol Metab. 2008;93:2243–8.

    Article  PubMed  CAS  Google Scholar 

  20. Fatti LM, Scacchi M, Lavezzi E, et al. Effects of treatment with somatostatin analogues on QT interval duration in acromegalic patients. Clin Endocrinol. 2006;65:626–30.

    Article  CAS  Google Scholar 

  21. Ayuk J, Clayton RN, Holder G, et al. Growth hormone and pituitary radiotherapy, but not serum insulin-like growth factor-I concentrations, predict excess mortality in patients with acromegaly. J Clin Endocrinol Metab. 2004;89:1613–7.

    Article  PubMed  CAS  Google Scholar 

  22. Sherlock M, Reulen RC, Aragon Alonso A, et al. ACTH deficiency, higher doses of hydrocortisone replacement, and radiotherapy are independent predictors of mortality in patients with acromegaly. J Clin Endocrinol Metab. 2009;94:4216–23.

    Article  PubMed  CAS  Google Scholar 

  23. Resmini E, Minuto F, Colao A, et al. Secondary diabetes associated with principal endocrinopathies: the impact of new treatment modalities. Acta Diabetes. 2009;46:85–95.

    Article  CAS  Google Scholar 

  24. Coculescu M, Niculescu D, Lichiardopol R, et al. Insulin resistance and insulin secretion in non-diabetic acromegalic patients. Exp Clin Endocrinol Metab. 2007;115:308–16.

    Article  CAS  Google Scholar 

  25. Jaffrain-Rea ML, Moroni C, Baldelli R, et al. Relationship between blood pressure and glucose tolerance in acromegaly. Clin Endocrinol. 2001;54:189–95.

    Article  CAS  Google Scholar 

  26. Mercado M, Gonzalez B, Sandoval C, et al. Clinical and biochemical impact of the d3 growth hormone receptor genotype in acromegaly. J Clin Endocrinol Metab. 2008;93:3411–5.

    Article  PubMed  CAS  Google Scholar 

  27. Rajasoorya C, Holdaway IM, Wrightson P, et al. Determinants of clinical outcome and survival in acromegaly. Clin Endocrinol. 1994;41:95–102.

    Article  CAS  Google Scholar 

  28. Arita K, Kurisu K, Tominaga A, et al. Mortality in 154 surgically treated patients with acromegaly – a 10-year follow-up survey. Endocr J. 2003;50:163–72.

    Article  PubMed  Google Scholar 

  29. Puder JJ, Nilavar S, Post KD, et al. Relationship between disease-related morbidity and biochemical markers of activity in patients with acromegaly. J Clin Endocrinol Metab. 2005;90:1972–8.

    Article  PubMed  CAS  Google Scholar 

  30. Hodish I, Barkan A. Long-term effects of pegvisomant in patients with acromegaly. Nat Clin Pract Endocrinol Metab. 2008;4:324–32.

    PubMed  CAS  Google Scholar 

  31. Bex M, Abs R, T’Sjoen G, et al. AcroBel – the Belgian registry on acromegaly: a survey of the “real-life” outcome on 418 acromegalic subjects. Eur J Endocrinol. 2007;157:399–409.

    Article  PubMed  CAS  Google Scholar 

  32. Biermasz NR, Pereira AM, Smit JWA, et al. Morbidity after long-term remission for acromegaly: persisting joint-related complaints cause reduced quality of life. J Clin Endocrinol Metab. 2005;90:2731–9.

    Article  PubMed  CAS  Google Scholar 

  33. Dons RF, Rosselet P, Pastakia B, et al. Arthropathy in acromegalic patients before and after treatment: a long-term follow-up study. Clin Endocrinol. 1988;28:515–24.

    Article  CAS  Google Scholar 

  34. Maffei P, Schiavon F, Ragazzi R, et al. Shoulder arthropathy in acromegaly. Abstracts of the 85th annual meeting US endocrinol society. 2003. p. P1–639.

    Google Scholar 

  35. Mazziotti G, Bianchi A, Bonadonna S, et al. Prevalence of vertebral fractures in men with acromegaly. J Clin Endocrinol Metab. 2008;93:4649–55.

    Article  PubMed  CAS  Google Scholar 

  36. Colao A, Cannavo S, Marzullo P, et al. Twelve months of treatment with octreotide-LAR reduces joint thickness in acromegaly. Eur J Endocrinol. 2003;148:31–8.

    Article  PubMed  CAS  Google Scholar 

  37. Roddam AW, Allen NE, Appleby P, et al. Insulin-like growth factors, their binding proteins, and prostate cancer risk: an analysis of individual patient data from 12 prospective studies. Ann Int Med. 2008;149:461–71.

    PubMed  Google Scholar 

  38. Renehan AG, Zwahlen M, Minder C, et al. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. 2004;363:1346–53.

    Article  PubMed  CAS  Google Scholar 

  39. Orme SM, McNally RJ, Cartwright RA, et al. Mortality and cancer incidence in acromegaly: a retrospective cohort study. United Kingdom Acromegaly Study Group. J Clin Endocrinol Metab. 1998;83:2730–4.

    Article  PubMed  CAS  Google Scholar 

  40. Renehan A, Bhaskar P, Painter JE, et al. The prevalence and characteristics of colorectal neoplasia in acromegaly. J Clin Endocrinol Metab. 2000;85:3417–24.

    Article  PubMed  CAS  Google Scholar 

  41. Bengtsson B-A, Eden S, Ernest I, et al. Epidemiology and long-term survival in acromegaly. Acta Med Scand. 1988;223:327–35.

    Article  PubMed  CAS  Google Scholar 

  42. Jones A. Radiation oncogenesis in relation to the treatment of pituitary tumours. Clin Endocrinol. 1991;35:379–97.

    Article  CAS  Google Scholar 

  43. Rokkas T, Pistiolas D, Sechopoulos P, et al. Risk of colorectal neoplasm in patients with acromegaly: a meta-analysis. World J Gastroenterol. 2008;14:3484–9.

    Article  PubMed  Google Scholar 

  44. Van Haute FRB, Taboada GF, Correa LL, et al. Prevalence of sleep apnea and metabolic abnormalities in patients with acromegaly and analysis of cephalometric parameters by magnetic resonance imaging. Eur J Endocrinol. 2008;158:459–65.

    Article  PubMed  Google Scholar 

  45. Sze L, Schmid C, Bloch KE, et al. Effect of transsphenoidal surgery on sleep apnoea in acromegaly. Eur J Endocrinol. 2007;156:321–9.

    Article  PubMed  CAS  Google Scholar 

  46. Wright AD, Hill DM, Lowy C, et al. Mortality in acromegaly. Q J Med. 1970;39:1–16.

    PubMed  CAS  Google Scholar 

  47. Bates AS, Van’t Hoff W, Jones JM, et al. An audit of outcome of treatment in acromegaly. Q J Med. 1993;86:293–9.

    PubMed  CAS  Google Scholar 

  48. Levy MJ, Matharu MS, Meeran K, et al. The clinical characteristics of headache in patients with pituitary tumours. Brain. 2005;128:1921–30.

    Article  PubMed  CAS  Google Scholar 

  49. Mestron A, Webb SM, Astorga R, et al. Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de Acromegalia, REA). Eur J Endocrinol. 2004;151:439–46.

    Article  PubMed  CAS  Google Scholar 

  50. Beauregard C, Truong U, Hardy J, et al. Long-term outcome and mortality after transsphenoidal adenomectomy for acromegaly. Clin Endocrinol. 2003;58:86–91.

    Article  Google Scholar 

  51. Trepp R, Stettler C, Zwahlen M, et al. Treatment outcomes and mortality of 94 patients with acromegaly. Acta Neurochir (Wien). 2005;147:243–51.

    Article  CAS  Google Scholar 

  52. Kauppinen-Makelin R, Sane T, Reunanen A, et al. A nationwide survey of mortality in acromegaly. J Clin Endocrinol Metab. 2005;90:4081–6.

    Article  PubMed  Google Scholar 

  53. Alexander L, Appleton D, Hall R, et al. Epidemiology of acromegaly in the Newcastle region. Clin Endocrinol. 1980;12:71–9.

    Article  CAS  Google Scholar 

  54. Dekkers OM, Biermasz NR, Pereira AM, et al. Mortality in acromegaly: a meta-analysis. J Clin Endocrinol Metab. 2008;93:61–7.

    Article  PubMed  CAS  Google Scholar 

  55. Holdaway IM, Bolland MJ, Gamble GD. A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly. Eur J Endocrinol. 2008;159:89–95.

    Article  PubMed  CAS  Google Scholar 

  56. Bengtsson BA, Jonsson B, Nilsson B. Increased mortality in acromegaly is mainly caused by cardiovascular diseases. Abstracts of the 81st annual scientific meeting US endocrine society. 1999. p. P3–648.

    Google Scholar 

  57. Etxabe J, Gaztambide S, Latorre P, et al. Acromegaly: an epidemiological study. J Endocrinol Invest. 1993;16:181–7.

    PubMed  CAS  Google Scholar 

  58. Abosch A, Tyrrell JB, Lamborn KR, et al. Transsphenoidal microsurgery for growth hormone-secreting pituitary adenomas: initial outcome and long-term results. J Clin Endocrinol Metab. 1998;83:3411–8.

    Article  PubMed  CAS  Google Scholar 

  59. Biermasz NR, Dekker FW, Pereira AM, et al. Determinants of survival in treated acromegaly in a single center: predictive value of serial insulin-like growth factor I measurements. J Clin Endocrinol Metab. 2004;89:2789–96.

    Article  PubMed  CAS  Google Scholar 

  60. Shimatsu A, Yokogoshi Y, Saito S, et al. Long-term survival and cardiovascular complications in patients with acromegaly and pituitary gigantism. J Endocrinol Invest. 1998;21:55–7.

    Google Scholar 

  61. Swearingen B, Barker FG, Katznelson L, et al. Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J Clin Endocrinol Metab. 1998;83:3419–26.

    Article  PubMed  CAS  Google Scholar 

  62. Holdaway IM. Excess mortality in acromegaly. Horm Res. 2007;68 Suppl 5:166–72.

    Article  PubMed  Google Scholar 

  63. Sherlock M, Aragon Alonso A, Reulen RC, et al. Monitoring disease activity using GH and IGF-I in the follow-up of 501 patients with acromegaly. Clin Endocrinol. 2009;71:74–81.

    Article  CAS  Google Scholar 

  64. Freda PU. Monitoring of acromegaly: what should be performed when GH and IGF-I levels are discrepant? Clin Endocrinol. 2009;71:166–70.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology, Greenlane Clinical Centre and Auckland Hospital, Greenlane Road West, 92189, Auckland, New Zealand

    Ian M. Holdaway

Authors
  1. Ian M. Holdaway
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ian M. Holdaway .

Editor information

Editors and Affiliations

  1. Princess Alexandra Hospital &, The University of Queensland, Centres for Health Research, Ipswich Road Woolloongabba 199, Brisbane, 4102, Queensland, Australia

    Ken Ho

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Holdaway, I.M. (2011). Mortality and Morbidity in Acromegaly: Impact of Disease Control. In: Ho, K. (eds) Growth Hormone Related Diseases and Therapy. Contemporary Endocrinology. Humana Press. https://doi.org/10.1007/978-1-60761-317-6_16

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-317-6_16

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-60761-316-9

  • Online ISBN: 978-1-60761-317-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation