Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Drug Insight: primary medical therapy of acromegaly

Nature Clinical Practice Endocrinology & Metabolism volume 2, pages 109–117 (2006)Cite this article

Abstract

Acromegaly is an insidious disease that, in most cases, is a result of a pituitary adenoma that hypersecretes growth hormone (GH). The goals of therapy are to control excess GH secretion and limit, if not reverse, the long-term medical consequences and risk of premature mortality associated with acromegaly. Surgery is currently the preferred primary therapeutic option because it can lead to rapid reductions in GH levels and prevent mass effects from local tumor growth. Medical therapy is used most often in an adjuvant, secondary role for patients in whom surgery has been unsuccessful. Radiation therapy is most commonly recommended in the setting of failed surgery and lack of adequate control with medical therapy. A role of primary medical therapy for patients de novo has been proposed, particularly with regard to somatostatin analogues. These analogues may control GH levels and reduce tumor volume in up to 50% of subjects, suggesting that they may be efficacious in this context. The use of somatostatin analogues to improve surgical outcome has also been proposed, but there is a lack of randomized trials available to address this issue. Primary medical therapy is well tolerated and further studies are necessary to identify patients who should be targeted for such therapy.

Key Points

  • The goal of therapy for acromegaly is to control both growth-hormone hypersecretion and tumor size; this leads to reversal of, or improvement in, the long-term morbidity and mortality associated with this disease

  • Medical therapy is largely relegated to an adjuvant role for patients who have active disease following surgical intervention

  • Medical therapy, especially with somatostatin analogues, has been proposed as primary, de novo therapy for acromegaly, in lieu of surgery

  • As discussed in this review, somatostatin analogues can be effective as primary medical therapy

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Alexander L et al. (1980) Epidemiology of acromegaly in the Newcastle region. Clin Endocrinol (Oxf) 12: 71–79

    CAS  Google Scholar 

  2. Colao A et al. (2004) Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev 25: 102–152

    CAS  PubMed  Google Scholar 

  3. Katznelson L (2005) Diagnosis and treatment of acromegaly. Growth Horm IGF Res 15 (Suppl 1): S31–S35

    CAS  PubMed  Google Scholar 

  4. Melmed S (1990) Acromegaly. N Engl J Med 322: 966–977

    CAS  PubMed  Google Scholar 

  5. Molitch ME (1992) Clinical manifestations of acromegaly. Endocrinol Metab Clin North Am 21: 597–614

    CAS  PubMed  Google Scholar 

  6. Colao A et al. (2000) Cardiovascular effects of depot long-acting somatostatin analog Sandostatin LAR in acromegaly. J Clin Endocrinol Metab 85: 3132–3140

    CAS  PubMed  Google Scholar 

  7. Colao A et al. (2004) The heart: an end-organ of GH action. Eur J Endocrinol 151 (Suppl 1): S93–S101

    CAS  PubMed  Google Scholar 

  8. Grunstein RR et al. (1991) Sleep apnea in acromegaly. Ann Intern Med 115: 527–532

    CAS  PubMed  Google Scholar 

  9. Colao A et al. (2003) Reversal of acromegalic cardiomyopathy in young but not in middle-aged patients after 12 months of treatment with the depot long-acting somatostatin analogue octreotide. Clin Endocrinol (Oxf) 58: 169–176

    CAS  Google Scholar 

  10. Grunstein RR et al. (1994) Effect of octreotide, a somatostatin analog, on sleep apnea in patients with acromegaly. Ann Intern Med 121: 478–483

    CAS  PubMed  Google Scholar 

  11. Jenkins PJ (2004) Acromegaly and cancer. Horm Res 62 (Suppl 1): 108–115

    CAS  PubMed  Google Scholar 

  12. Pollak MN et al. (2004) Insulin-like growth factors and neoplasia. Nat Rev Cancer 4: 505–518

    CAS  PubMed  Google Scholar 

  13. Ron E et al. (1991) Acromegaly and gastrointestinal cancer. Cancer 68: 1673–1677

    CAS  PubMed  Google Scholar 

  14. Delhougne B et al. (1995) The prevalence of colonic polyps in acromegaly: a colonoscopic and pathological study in 103 patients. J Clin Endocrinol Metab 80: 3223–3226

    CAS  PubMed  Google Scholar 

  15. Bengtsson BA et al. (1988) Epidemiology and long-term survival in acromegaly. A study of 166 cases diagnosed between 1955 and 1984. Acta Med Scand 223: 327–335

    CAS  PubMed  Google Scholar 

  16. Abosch A et al. (1998) Trans-sphenoidal microsurgery for growth hormone-secreting pituitary adenomas: initial outcome and long-term results. J Clin Endocrinol Metab 83: 3411–3418

    CAS  PubMed  Google Scholar 

  17. Swearingen B et al. (1998) Long-term mortality after trans-sphenoidal surgery and adjunctive therapy for acromegaly. J Clin Endocrinol Metab 83: 3419–3426

    CAS  PubMed  Google Scholar 

  18. Holdaway IM et al. (2004) Factors influencing mortality in acromegaly. J Clin Endocrinol Metab 89: 667–674

    CAS  PubMed  Google Scholar 

  19. Barker FG Jr et al. (2003) Trans-sphenoidal surgery for pituitary tumors in the United States, 1996–2000: mortality, morbidity, and the effects of hospital and surgeon volume. J Clin Endocrinol Metab 88: 4709–4719

    CAS  PubMed  Google Scholar 

  20. Fahlbusch R et al. (1992) Surgical management of acromegaly. Endocrinol Metab Clin North Am 21: 669–692

    CAS  PubMed  Google Scholar 

  21. Nomikos P et al. (2005) The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical 'cure'. Eur J Endocrinol 152: 379–387

    CAS  PubMed  Google Scholar 

  22. Sheaves R et al. (1996) Outcome of trans-sphenoidal surgery for acromegaly using strict criteria for surgical cure. Clin Endocrinol (Oxf) 45: 407–413

    CAS  Google Scholar 

  23. Biermasz NR et al. (2000) Long-term follow-up results of postoperative radiotherapy in 36 patients with acromegaly. J Clin Endocrinol Metab 85: 2476–2482

    CAS  PubMed  Google Scholar 

  24. Powell JS et al. (2000) Outcome of radiotherapy for acromegaly using normalization of insulin-like growth factor I to define cure. J Clin Endocrinol Metab 85: 2068–2071

    CAS  PubMed  Google Scholar 

  25. Barkan AL et al. (1997) Pituitary irradiation is ineffective in normalizing plasma insulin-like growth factor I in patients with acromegaly. J Clin Endocrinol Metab 82: 3187–3191

    CAS  PubMed  Google Scholar 

  26. Landolt AM et al. (1998) Stereotactic radiosurgery for recurrent surgically treated acromegaly: comparison with fractionated radiotherapy. J Neurosurg 88: 1002–1008

    CAS  PubMed  Google Scholar 

  27. Castinetti F et al. (2005) Outcome of gamma knife radiosurgery in 82 patients with acromegaly: correlation with initial hypersecretion. J Clin Endocrinol Metab 90: 4483–4488

    CAS  PubMed  Google Scholar 

  28. Freda PU et al. (2005) Long-acting somatostatin analog therapy of acromegaly: a meta-analysis. J Clin Endocrinol Metab 90: 4465–4473

    CAS  PubMed  Google Scholar 

  29. Colao A et al. (1996) Prediction of efficacy of octreotide therapy in patients with acromegaly. J Clin Endocrinol Metab 81: 2356–2362

    CAS  PubMed  Google Scholar 

  30. Bevan JS et al. (2002) Primary medical therapy for acromegaly: an open, prospective, multicenter study of the effects of subcutaneous and intramuscular slow-release octreotide on growth hormone, insulin-like growth factor-I, and tumor size. J Clin Endocrinol Metab 87: 4554–4563

    CAS  PubMed  Google Scholar 

  31. Saveanu A et al. (2002) Demonstration of enhanced potency of a chimeric somatostatin-dopamine molecule, BIM-23A387, in suppressing growth hormone and prolactin secretion from human pituitary somatotroph adenoma cells. J Clin Endocrinol Metab 87: 5545–5552

    CAS  PubMed  Google Scholar 

  32. Colao A et al. (1997) Effect of different dopaminergic agents in the treatment of acromegaly. J Clin Endocrinol Metab 82: 518–523

    CAS  PubMed  Google Scholar 

  33. Abs R et al. (1998) Cabergoline in the treatment of acromegaly: a study in 64 patients. J Clin Endocrinol Metab 83: 374–378

    CAS  PubMed  Google Scholar 

  34. Trainer PJ et al. (2000) Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med 342: 1171–1177

    CAS  PubMed  Google Scholar 

  35. van der Lely AJ et al. (2001) Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet 358: 1754–1759

    CAS  PubMed  Google Scholar 

  36. Herman-Bonert VS et al. (2000) Growth hormone receptor antagonist therapy in acromegalic patients resistant to somatostatin analogs. J Clin Endocrinol Metab 85: 2958–2961

    CAS  PubMed  Google Scholar 

  37. van der Lely AJ et al. (2001) Control of tumor size and disease activity during cotreatment with octreotide and the growth hormone receptor antagonist pegvisomant in an acromegalic patient. J Clin Endocrinol Metab 86: 478–481

    CAS  PubMed  Google Scholar 

  38. Barkan AL et al. (2005) Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant. J Clin Endocrinol Metab 90: 5684–5691

    CAS  PubMed  Google Scholar 

  39. Holdaway IM (2004) Treatment of acromegaly. Horm Res 62 (Suppl 3): 79–92

    CAS  PubMed  Google Scholar 

  40. Feenstra J et al. (2005) Combined therapy with somatostatin analogues and weekly pegvisomant in active acromegaly. Lancet 365: 1644–1646

    CAS  PubMed  Google Scholar 

  41. Ayuk J et al. (2004) Efficacy of sandostatin LAR (long-acting somatostatin analogue) is similar in patients with untreated acromegaly and in those previously treated with surgery and/or radiotherapy. Clin Endocrinol (Oxf) 60: 375–381

    CAS  Google Scholar 

  42. Newman CB et al. (1998) Octreotide as primary therapy for acromegaly. J Clin Endocrinol Metab 83: 3034–3040

    CAS  PubMed  Google Scholar 

  43. Lucas T et al. (2003) Preoperative lanreotide treatment for GH-secreting pituitary adenomas: effect on tumour volume and predictive factors of significant tumour shrinkage. Clin Endocrinol (Oxf) 58: 471–481

    CAS  Google Scholar 

  44. Amato G et al. (2002) Long-term effects of lanreotide SR and octreotide LAR on tumour shrinkage and GH hypersecretion in patients with previously untreated acromegaly. Clin Endocrinol (Oxf) 56: 65–71

    CAS  Google Scholar 

  45. Melmed S et al. (2005) A critical analysis of pituitary tumor shrinkage during primary medical therapy in acromegaly. J Clin Endocrinol Metab 90: 4405–4410

    CAS  PubMed  Google Scholar 

  46. Bevan JS (2005) Clinical review: the antitumoral effects of somatostatin analog therapy in acromegaly. J Clin Endocrinol Metab 90: 1856–1863

    CAS  PubMed  Google Scholar 

  47. Resmini E et al. (2005) Pituitary tumor disappearance in a patient with newly diagnosed acromegaly primarily treated with octreotide LAR. J Endocrinol Invest 28: 166–169

    CAS  PubMed  Google Scholar 

  48. Abe T and Ludecke DK (2001) Effects of preoperative octreotide treatment on different subtypes of 90 GH-secreting pituitary adenomas and outcome in one surgical centre. Eur J Endocrinol 145: 137–145

    CAS  PubMed  Google Scholar 

  49. Colao A et al. (2001) Long-term effects of depot long-acting somatostatin analog octreotide on hormone levels and tumor mass in acromegaly. J Clin Endocrinol Metab 86: 2779–2786

    CAS  PubMed  Google Scholar 

  50. Lundin P et al. (1997) Long-term octreotide therapy in growth hormone-secreting pituitary adenomas: evaluation with serial MR. AJNR Am J Neuroradiol 18: 765–772

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Danila DC et al. (2001) Somatostatin receptor-specific analogs: effects on cell proliferation and growth hormone secretion in human somatotroph tumors. J Clin Endocrinol Metab 86: 2976–2981

    CAS  PubMed  Google Scholar 

  52. Rickels MR and Snyder PJ (2004) Cabergoline decreases somatotroph adenoma size: a case report. Pituitary 7: 107–110

    PubMed  Google Scholar 

  53. Petrossians P et al. (2005) Gross total resection or debulking of pituitary adenomas improves hormonal control of acromegaly by somatostatin analogs. Eur J Endocrinol 152: 61–66

    CAS  PubMed  Google Scholar 

  54. Colao A et al. (1997) Effect of octreotide pretreatment on surgical outcome in acromegaly. J Clin Endocrinol Metab 82: 3308–3314

    CAS  PubMed  Google Scholar 

  55. Yin J et al. (2005) Effect of preoperative use of long-acting octreotide on growth hormone secreting pituitary adenoma and trans-sphenoidal surgery. Chin Med Sci J 20: 23–26

    CAS  PubMed  Google Scholar 

  56. Tamura M et al. (1998) Preoperative treatment of growth hormone-producing pituitary adenoma with continuous subcutaneous infusion of octreotide. Endocr J 45: 269–275

    CAS  PubMed  Google Scholar 

  57. Barkan AL et al. (1988) Preoperative treatment of acromegaly with long-acting somatostatin analog SMS 201-995: shrinkage of invasive pituitary macroadenomas and improved surgical remission rate. J Clin Endocrinol Metab 67: 1040–1048

    CAS  PubMed  Google Scholar 

  58. Tachibana E et al. (1999) Preoperative short-term administration of octreotide for facilitating trans-sphenoidal removal of invasive growth hormone-secreting macroadenomas. Neurol Med Chir (Tokyo) 39: 496–499

    CAS  Google Scholar 

  59. Stevenaert A and Beckers A (1996) Presurgical octreotide: treatment in acromegaly. Metabolism 45 (Suppl 1): 72–74

    CAS  PubMed  Google Scholar 

  60. Biermasz NR et al. (1999) Direct postoperative and follow-up results of trans-sphenoidal surgery in 19 acromegalic patients pretreated with octreotide compared to those in untreated matched controls. J Clin Endocrinol Metab 84: 3551–3555

    CAS  PubMed  Google Scholar 

  61. Kristof RA et al. (1999) Does octreotide treatment improve the surgical results of macro-adenomas in acromegaly? A randomized study. Acta Neurochir (Wien) 141: 399–405

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Associate Professor of Neurosurgery and Medicine at Stanford University School of Medicine, Stanford, USA

    Laurence Katznelson

Authors
  1. Laurence Katznelson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Laurence Katznelson.

Ethics declarations

Competing interests

The author receives support from the Speakers Bureau, Pfizer, and Unrestricted Education Grants from Novartis and Ipsen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Katznelson, L. Drug Insight: primary medical therapy of acromegaly. Nat Rev Endocrinol 2, 109–117 (2006). https://doi.org/10.1038/ncpendmet0096

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpendmet0096

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing