Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Treatment of acromegaly

Shlomo Melmed, MD
Laurence Katznelson, MD
Section Editor
Peter J Snyder, MD
Deputy Editor
Kathryn A Martin, MD


Acromegaly is almost always caused by a somatotroph (growth hormone [GH]-secreting) adenoma of the pituitary gland and is associated with increased morbidity and mortality. As a result, almost all patients should be treated, even those who are asymptomatic and those in whom the disorder does not seem to be progressing. One exception is a patient with a short life expectancy who is not expected to live long enough to benefit from therapy.

The treatment of acromegaly will be reviewed here. The clinical manifestations and diagnosis of acromegaly are discussed separately. (See "Causes and clinical manifestations of acromegaly" and "Diagnosis of acromegaly".)


The goals of therapy in patients with acromegaly are to lower the serum insulin-like growth factor-1 (IGF-1) concentration to within the normal range for the patient's age and gender, control adenoma size and reduce mass effects, improve symptoms, and reverse metabolic abnormalities such as diabetes mellitus [1]. (See "Causes and clinical manifestations of acromegaly", section on 'Metabolic'.)

In addition to lowering IGF-1, another biochemical goal is to lower the serum growth hormone (GH) concentration to <1.0 mcg/L as measured by immunoradiometric or chemiluminescent assay, as this also correlates with control of acromegaly. [2]. However, the IGF-1 criterion may be better since some patients who appear to have active disease clinically and by elevated IGF-1 concentration have serum GH values that suppress to <1.0 mcg/L [3,4]. Serum IGF-1 concentrations also correlate better than serum GH with insulin sensitivity in patients with acromegaly [5]. (See 'Biochemical outcomes' below.)

When serum GH and IGF-1 concentrations decline to normal [6], the characteristic soft tissue overgrowth and related symptoms gradually recede and the metabolic abnormalities, such as diabetes mellitus, improve. In addition, life expectancy returns to that of the general population [7,8]. However, bony abnormalities generally do not regress and joint symptoms persist. (See 'Amelioration of symptoms' below.)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Dec 08, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Melmed S. Acromegaly pathogenesis and treatment. J Clin Invest 2009; 119:3189.
  2. Katznelson L, Laws ER Jr, Melmed S, et al. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2014; 99:3933.
  3. Freda PU, Post KD, Powell JS, Wardlaw SL. Evaluation of disease status with sensitive measures of growth hormone secretion in 60 postoperative patients with acromegaly. J Clin Endocrinol Metab 1998; 83:3808.
  4. Dimaraki EV, Jaffe CA, DeMott-Friberg R, et al. Acromegaly with apparently normal GH secretion: implications for diagnosis and follow-up. J Clin Endocrinol Metab 2002; 87:3537.
  5. Puder JJ, Nilavar S, Post KD, Freda PU. Relationship between disease-related morbidity and biochemical markers of activity in patients with acromegaly. J Clin Endocrinol Metab 2005; 90:1972.
  6. Melmed S. Medical progress: Acromegaly. N Engl J Med 2006; 355:2558.
  7. Swearingen B, Barker FG 2nd, Katznelson L, et al. Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J Clin Endocrinol Metab 1998; 83:3419.
  8. 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.
  9. Freda PU, Wardlaw SL, Post KD. Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly. J Neurosurg 1998; 89:353.
  10. Ronchi CL, Giavoli C, Ferrante E, et al. Prevalence of GH deficiency in cured acromegalic patients: impact of different previous treatments. Eur J Endocrinol 2009; 161:37.
  11. Ross DA, Wilson CB. Results of transsphenoidal microsurgery for growth hormone-secreting pituitary adenoma in a series of 214 patients. J Neurosurg 1988; 68:854.
  12. Ciric I, Ragin A, Baumgartner C, Pierce D. Complications of transsphenoidal surgery: results of a national survey, review of the literature, and personal experience. Neurosurgery 1997; 40:225.
  13. Barker FG 2nd, Klibanski A, Swearingen B. Transsphenoidal surgery for pituitary tumors in the United States, 1996-2000: mortality, morbidity, and the effects of hospital and surgeon volume. J Clin Endocrinol Metab 2003; 88:4709.
  14. Ahmed M, Kanaan I, Rifai A, et al. An unusual treatment-related complication in a patient with growth hormone-secreting pituitary tumor. J Clin Endocrinol Metab 1997; 82:2816.
  15. Fahlbusch R, Honegger J, Buchfelder M. Surgical management of acromegaly. Endocrinol Metab Clin North Am 1992; 21:669.
  16. Jenkins D, O'Brien I, Johnson A, et al. The Birmingham pituitary database: auditing the outcome of the treatment of acromegaly. Clin Endocrinol (Oxf) 1995; 43:517.
  17. Feelders RA, Bidlingmaier M, Strasburger CJ, et al. Postoperative evaluation of patients with acromegaly: clinical significance and timing of oral glucose tolerance testing and measurement of (free) insulin-like growth factor I, acid-labile subunit, and growth hormone-binding protein levels. J Clin Endocrinol Metab 2005; 90:6480.
  18. Sze L, Schmid C, Bloch KE, et al. Effect of transsphenoidal surgery on sleep apnoea in acromegaly. Eur J Endocrinol 2007; 156:321.
  19. Colao A, Marzullo P, Vallone G, et al. Reversibility of joint thickening in acromegalic patients: an ultrasonography study. J Clin Endocrinol Metab 1998; 83:2121.
  20. Biermasz NR, Pereira AM, Smit JW, 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.
  21. Wexler T, Gunnell L, Omer Z, et al. Growth hormone deficiency is associated with decreased quality of life in patients with prior acromegaly. J Clin Endocrinol Metab 2009; 94:2471.
  22. Miller KK, Wexler T, Fazeli P, et al. Growth hormone deficiency after treatment of acromegaly: a randomized, placebo-controlled study of growth hormone replacement. J Clin Endocrinol Metab 2010; 95:567.
  23. Norrman LL, Johannsson G, Sunnerhagen KS, Svensson J. Baseline characteristics and the effects of two years of growth hormone (GH) replacement therapy in adults with GH deficiency previously treated for acromegaly. J Clin Endocrinol Metab 2008; 93:2531.
  24. Caron P, Broussaud S, Bertherat J, et al. Acromegaly and pregnancy: a retrospective multicenter study of 59 pregnancies in 46 women. J Clin Endocrinol Metab 2010; 95:4680.
  25. Cheng S, Grasso L, Martinez-Orozco JA, et al. Pregnancy in acromegaly: experience from two referral centers and systematic review of the literature. Clin Endocrinol (Oxf) 2012; 76:264.
  26. van der Lely AJ, Gomez R, Heissler JF, et al. Pregnancy in acromegaly patients treated with pegvisomant. Endocrine 2015; 49:769.
  27. Frankenne F, Closset J, Gomez F, et al. The physiology of growth hormones (GHs) in pregnant women and partial characterization of the placental GH variant. J Clin Endocrinol Metab 1988; 66:1171.
  28. Eriksson L, Frankenne F, Edèn S, et al. Growth hormone 24-h serum profiles during pregnancy--lack of pulsatility for the secretion of the placental variant. Br J Obstet Gynaecol 1989; 96:949.
  29. Grynberg M, Salenave S, Young J, Chanson P. Female gonadal function before and after treatment of acromegaly. J Clin Endocrinol Metab 2010; 95:4518.
  30. Starke RM, Raper DM, Payne SC, et al. Endoscopic vs microsurgical transsphenoidal surgery for acromegaly: outcomes in a concurrent series of patients using modern criteria for remission. J Clin Endocrinol Metab 2013; 98:3190.
  31. Babu H, Ortega A, Nuno M, et al. Long-Term Endocrine Outcomes Following Endoscopic Endonasal Transsphenoidal Surgery for Acromegaly and Associated Prognostic Factors. Neurosurgery 2017; 81:357.
  32. Ben-Shlomo A, Melmed S. Clinical review 154: The role of pharmacotherapy in perioperative management of patients with acromegaly. J Clin Endocrinol Metab 2003; 88:963.
  33. Jane JA Jr, Starke RM, Elzoghby MA, et al. Endoscopic transsphenoidal surgery for acromegaly: remission using modern criteria, complications, and predictors of outcome. J Clin Endocrinol Metab 2011; 96:2732.
  34. Hofstetter CP, Mannaa RH, Mubita L, et al. Endoscopic endonasal transsphenoidal surgery for growth hormone-secreting pituitary adenomas. Neurosurg Focus 2010; 29:E6.
  35. Kreutzer J, Vance ML, Lopes MB, Laws ER Jr. Surgical management of GH-secreting pituitary adenomas: an outcome study using modern remission criteria. J Clin Endocrinol Metab 2001; 86:4072.
  36. Biermasz NR, van Dulken H, Roelfsema F. Ten-year follow-up results of transsphenoidal microsurgery in acromegaly. J Clin Endocrinol Metab 2000; 85:4596.
  37. Freda PU, Nuruzzaman AT, Reyes CM, et al. Significance of "abnormal" nadir growth hormone levels after oral glucose in postoperative patients with acromegaly in remission with normal insulin-like growth factor-I levels. J Clin Endocrinol Metab 2004; 89:495.
  38. Cozzi R, Montini M, Attanasio R, et al. Primary treatment of acromegaly with octreotide LAR: a long-term (up to nine years) prospective study of its efficacy in the control of disease activity and tumor shrinkage. J Clin Endocrinol Metab 2006; 91:1397.
  39. Shimon I, Yan X, Taylor JE, et al. Somatostatin receptor (SSTR) subtype-selective analogues differentially suppress in vitro growth hormone and prolactin in human pituitary adenomas. Novel potential therapy for functional pituitary tumors. J Clin Invest 1997; 100:2386.
  40. Taboada GF, Luque RM, Neto LV, et al. Quantitative analysis of somatostatin receptor subtypes (1-5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR. Eur J Endocrinol 2008; 158:295.
  41. Fougner SL, Casar-Borota O, Heck A, et al. Adenoma granulation pattern correlates with clinical variables and effect of somatostatin analogue treatment in a large series of patients with acromegaly. Clin Endocrinol (Oxf) 2012; 76:96.
  42. Melmed S. New therapeutic agents for acromegaly. Nat Rev Endocrinol 2016; 12:90.
  43. Thapar K, Kovacs KT, Stefaneanu L, et al. Antiproliferative effect of the somatostatin analogue octreotide on growth hormone-producing pituitary tumors: results of a multicenter randomized trial. Mayo Clin Proc 1997; 72:893.
  44. Losa M, Ciccarelli E, Mortini P, et al. Effects of octreotide treatment on the proliferation and apoptotic index of GH-secreting pituitary adenomas. J Clin Endocrinol Metab 2001; 86:5194.
  45. Caron P, Beckers A, Cullen DR, et al. Efficacy of the new long-acting formulation of lanreotide (lanreotide Autogel) in the management of acromegaly. J Clin Endocrinol Metab 2002; 87:99.
  46. Giustina A, Mazziotti G, Cannavò S, et al. High-Dose and High-Frequency Lanreotide Autogel in Acromegaly: A Randomized, Multicenter Study. J Clin Endocrinol Metab 2017; 102:2454.
  47. Giustina A, Bonadonna S, Bugari G, et al. High-dose intramuscular octreotide in patients with acromegaly inadequately controlled on conventional somatostatin analogue therapy: a randomised controlled trial. Eur J Endocrinol 2009; 161:331.
  48. Murray RD, Melmed S. A critical analysis of clinically available somatostatin analog formulations for therapy of acromegaly. J Clin Endocrinol Metab 2008; 93:2957.
  49. Larkin S, Reddy R, Karavitaki N, et al. Granulation pattern, but not GSP or GHR mutation, is associated with clinical characteristics in somatostatin-naive patients with somatotroph adenomas. Eur J Endocrinol 2013; 168:491.
  50. Kiseljak-Vassiliades K, Shafi S, Kerr JM, et al. Clinical implications of growth hormone-secreting tumor subtypes. Endocrine 2012; 42:18.
  51. Heck A, Ringstad G, Fougner SL, et al. Intensity of pituitary adenoma on T2-weighted magnetic resonance imaging predicts the response to octreotide treatment in newly diagnosed acromegaly. Clin Endocrinol (Oxf) 2012; 77:72.
  52. Puig-Domingo M, Resmini E, Gomez-Anson B, et al. Magnetic resonance imaging as a predictor of response to somatostatin analogs in acromegaly after surgical failure. J Clin Endocrinol Metab 2010; 95:4973.
  53. Bevan JS, Atkin SL, Atkinson AB, et al. 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 2002; 87:4554.
  54. Freda PU. Somatostatin analogs in acromegaly. J Clin Endocrinol Metab 2002; 87:3013.
  55. Lamberts SW, Zweens M, Verschoor L, del Pozo E. A comparison among the growth hormone-lowering effects in acromegaly of the somatostatin analog SMS 201-995, bromocriptine, and the combination of both drugs. J Clin Endocrinol Metab 1986; 63:16.
  56. Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev 2004; 25:102.
  57. Grunstein RR, Ho KK, Sullivan CE. Effect of octreotide, a somatostatin analog, on sleep apnea in patients with acromegaly. Ann Intern Med 1994; 121:478.
  58. Herrmann BL, Wessendorf TE, Ajaj W, et al. Effects of octreotide on sleep apnoea and tongue volume (magnetic resonance imaging) in patients with acromegaly. Eur J Endocrinol 2004; 151:309.
  59. Lim MJ, Barkan AL, Buda AJ. Rapid reduction of left ventricular hypertrophy in acromegaly after suppression of growth hormone hypersecretion. Ann Intern Med 1992; 117:719.
  60. Colao A, Cuocolo A, Marzullo P, et al. Effects of 1-year treatment with octreotide on cardiac performance in patients with acromegaly. J Clin Endocrinol Metab 1999; 84:17.
  61. Maison P, Tropeano AI, Macquin-Mavier I, et al. Impact of somatostatin analogs on the heart in acromegaly: a metaanalysis. J Clin Endocrinol Metab 2007; 92:1743.
  62. Melmed S, Sternberg R, Cook D, et al. A critical analysis of pituitary tumor shrinkage during primary medical therapy in acromegaly. J Clin Endocrinol Metab 2005; 90:4405.
  63. Colao A, Pivonello R, Auriemma RS, et al. Predictors of tumor shrinkage after primary therapy with somatostatin analogs in acromegaly: a prospective study in 99 patients. J Clin Endocrinol Metab 2006; 91:2112.
  64. Lamberts SW, van der Lely AJ, de Herder WW, Hofland LJ. Octreotide. N Engl J Med 1996; 334:246.
  65. Grasso LF, Auriemma RS, Pivonello R, Colao A. Adverse events associated with somatostatin analogs in acromegaly. Expert Opin Drug Saf 2015; 14:1213.
  66. Mazziotti G, Floriani I, Bonadonna S, et al. Effects of somatostatin analogs on glucose homeostasis: a metaanalysis of acromegaly studies. J Clin Endocrinol Metab 2009; 94:1500.
  67. Colao A, Bronstein MD, Freda P, et al. Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab 2014; 99:791.
  68. Melmed S, Popovic V, Bidlingmaier M, et al. Safety and efficacy of oral octreotide in acromegaly: results of a multicenter phase III trial. J Clin Endocrinol Metab 2015; 100:1699.
  69. Pradhananga S, Wilkinson I, Ross RJ. Pegvisomant: structure and function. J Mol Endocrinol 2002; 29:11.
  70. Jehle S, Reyes CM, Sundeen RE, Freda PU. Alternate-day administration of pegvisomant maintains normal serum insulin-like growth factor-I levels in patients with acromegaly. J Clin Endocrinol Metab 2005; 90:1588.
  71. Parkinson C, Burman P, Messig M, Trainer PJ. Gender, body weight, disease activity, and previous radiotherapy influence the response to pegvisomant. J Clin Endocrinol Metab 2007; 92:190.
  72. Trainer PJ, Drake WM, Katznelson L, et al. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med 2000; 342:1171.
  73. Biering H, Saller B, Bauditz J, et al. Elevated transaminases during medical treatment of acromegaly: a review of the German pegvisomant surveillance experience and a report of a patient with histologically proven chronic mild active hepatitis. Eur J Endocrinol 2006; 154:213.
  74. van der Lely AJ, Biller BM, Brue T, et al. Long-term safety of pegvisomant in patients with acromegaly: comprehensive review of 1288 subjects in ACROSTUDY. J Clin Endocrinol Metab 2012; 97:1589.
  75. Buhk JH, Jung S, Psychogios MN, et al. Tumor volume of growth hormone-secreting pituitary adenomas during treatment with pegvisomant: a prospective multicenter study. J Clin Endocrinol Metab 2010; 95:552.
  76. Trainer PJ. ACROSTUDY: the first 5 years. Eur J Endocrinol 2009; 161 Suppl 1:S19.
  77. Bonert VS, Kennedy L, Petersenn S, et al. Lipodystrophy in patients with acromegaly receiving pegvisomant. J Clin Endocrinol Metab 2008; 93:3515.
  78. Feenstra J, de Herder WW, ten Have SM, et al. Combined therapy with somatostatin analogues and weekly pegvisomant in active acromegaly. Lancet 2005; 365:1644.
  79. Trainer PJ, Ezzat S, D'Souza GA, et al. A randomized, controlled, multicentre trial comparing pegvisomant alone with combination therapy of pegvisomant and long-acting octreotide in patients with acromegaly. Clin Endocrinol (Oxf) 2009; 71:549.
  80. Madsen M, Poulsen PL, Orskov H, et al. Cotreatment with pegvisomant and a somatostatin analog (SA) in SA-responsive acromegalic patients. J Clin Endocrinol Metab 2011; 96:2405.
  81. Sandret L, Maison P, Chanson P. Place of cabergoline in acromegaly: a meta-analysis. J Clin Endocrinol Metab 2011; 96:1327.
  82. Abs R, Verhelst J, Maiter D, et al. Cabergoline in the treatment of acromegaly: a study in 64 patients. J Clin Endocrinol Metab 1998; 83:374.
  83. Loeffler JS, Shih HA. Radiation therapy in the management of pituitary adenomas. J Clin Endocrinol Metab 2011; 96:1992.
  84. Landolt AM, Haller D, Lomax N, et al. Octreotide may act as a radioprotective agent in acromegaly. J Clin Endocrinol Metab 2000; 85:1287.
  85. Castinetti F, Taieb D, Kuhn JM, et al. Outcome of gamma knife radiosurgery in 82 patients with acromegaly: correlation with initial hypersecretion. J Clin Endocrinol Metab 2005; 90:4483.
  86. Pollock BE, Jacob JT, Brown PD, Nippoldt TB. Radiosurgery of growth hormone-producing pituitary adenomas: factors associated with biochemical remission. J Neurosurg 2007; 106:833.
  87. Jenkins PJ, Bates P, Carson MN, et al. Conventional pituitary irradiation is effective in lowering serum growth hormone and insulin-like growth factor-I in patients with acromegaly. J Clin Endocrinol Metab 2006; 91:1239.
  88. Powell JS, Wardlaw SL, Post KD, Freda PU. Outcome of radiotherapy for acromegaly using normalization of insulin-like growth factor I to define cure. J Clin Endocrinol Metab 2000; 85:2068.
  89. Barrande G, Pittino-Lungo M, Coste J, et al. Hormonal and metabolic effects of radiotherapy in acromegaly: long-term results in 128 patients followed in a single center. J Clin Endocrinol Metab 2000; 85:3779.
  90. Cozzi R, Barausse M, Asnaghi D, et al. Failure of radiotherapy in acromegaly. Eur J Endocrinol 2001; 145:717.
  91. Epaminonda P, Porretti S, Cappiello V, et al. Efficacy of radiotherapy in normalizing serum IGF-I, acid-labile subunit (ALS) and IGFBP-3 levels in acromegaly. Clin Endocrinol (Oxf) 2001; 55:183.
  92. Thalassinos NC, Tsagarakis S, Ioannides G, et al. Megavoltage pituitary irradiation lowers but seldom leads to safe GH levels in acromegaly: a long-term follow-up study. Eur J Endocrinol 1998; 138:160.
  93. Jezková J, Marek J, Hána V, et al. Gamma knife radiosurgery for acromegaly--long-term experience. Clin Endocrinol (Oxf) 2006; 64:588.
  94. Ronchi CL, Attanasio R, Verrua E, et al. Efficacy and tolerability of gamma knife radiosurgery in acromegaly: a 10-year follow-up study. Clin Endocrinol (Oxf) 2009; 71:846.
  95. Lee CC, Vance ML, Xu Z, et al. Stereotactic radiosurgery for acromegaly. J Clin Endocrinol Metab 2014; 99:1273.
  96. Petit JH, Biller BM, Coen JJ, et al. Proton stereotactic radiosurgery in management of persistent acromegaly. Endocr Pract 2007; 13:726.
  97. Brada M, Ford D, Ashley S, et al. Risk of second brain tumour after conservative surgery and radiotherapy for pituitary adenoma. BMJ 1992; 304:1343.
  98. Tsang RW, Laperriere NJ, Simpson WJ, et al. Glioma arising after radiation therapy for pituitary adenoma. A report of four patients and estimation of risk. Cancer 1993; 72:2227.
  99. Sherlock M, Reulen RC, Alonso AA, 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.
  100. 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.