Highlights & Basics
- Acromegaly is a rare, chronic disease caused by excessive secretion of growth hormone (GH), usually due to a pituitary somatotroph adenoma. It is associated with increased morbidity and premature mortality if not appropriately treated.
- The diagnosis is often delayed. Early recognition and appropriate treatment are crucial for reducing the potentially debilitating complications of the disease.
- Must be screened for in the presence of pituitary adenoma, profuse sweating, acral growth, coarsening of facial features, and when suspected in conjunction with commonly associated conditions, such as carpal tunnel syndrome, arthralgia, glucose intolerance or diabetes mellitus, amenorrhea, hypertension, and sleep apnea.
- Modern surgical and pharmacologic modalities are associated with improved outcomes. Normalization of plasma insulin-like growth factor 1 (IGF-1) and a decrease of plasma GH to below 1 microgram/L bring the mortality rate to normal.
- Monitoring and treatment of the comorbidities associated with acromegaly are essential for improving patient quality of life.
Quick Reference
History & Exam
Key Factors
Other Factors
Diagnostics Tests
Treatment Options
Definition
Epidemiology
Etiology
Pathophysiology
Citations
Fleseriu M, Langlois F, Lim DST, et al. Acromegaly: pathogenesis, diagnosis, and management. Lancet Diabetes Endocrinol. 2022 Nov;10(11):804-26.[Abstract]
Katznelson L, Laws ER Jr, Melmed S, et al; Endocrine Society. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014 Nov;99(11):3933-51.[Abstract][Full Text]
Giustina A, Barkhoudarian G, Beckers A, et al. Multidisciplinary management of acromegaly: a consensus. Rev Endocr Metab Disord. 2020 Dec;21(4):667-78.[Abstract]
Fleseriu M, Biller BMK, Freda PU, et al. A Pituitary Society update to acromegaly management guidelines. Pituitary. 2021 Feb;24(1):1-13.[Abstract][Full Text]
Giustina A, Barkan A, Beckers A, et al. A consensus on the diagnosis and treatment of acromegaly comorbidities: an update. J Clin Endocrinol Metab. 2020 Apr 1;105(4):dgz096.[Abstract]
1. WHO Classification of Tumours Editorial Board. World Health Organization classification of tumours of the central nervous system. 5th ed. Lyon: International Agency for Research on Cancer; 2021.
2. Lopes MBS. The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. Acta Neuropathol. 2017 Oct;134(4):521-35.[Abstract]
3. Louis DN, Perry A, Wesseling P, et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol. 2021 Aug 2;23(8):1231-51.[Abstract][Full Text]
4. Fleseriu M, Langlois F, Lim DST, et al. Acromegaly: pathogenesis, diagnosis, and management. Lancet Diabetes Endocrinol. 2022 Nov;10(11):804-26.[Abstract]
5. Tritos NA, Miller KK. Diagnosis and management of pituitary adenomas: a review. JAMA. 2023 Apr 25;329(16):1386-98.[Abstract]
6. Horvath A, Stratakis CA. Clinical and molecular genetics of acromegaly: MEN-1, Carney complex, McCune-Albright syndrome, familial acromegaly and genetic defects in sporadic tumors. Rev Endocr Metab Disord. 2008;9:1-11.[Abstract]
7. Melmed S. Pituitary-tumor endocrinopathies. N Engl J Med. 2020 Mar 5;382(10):937-50.[Abstract]
8. Lavrentaki A, Paluzzi A, Wass JA, et al. Epidemiology of acromegaly: review of population studies. Pituitary. 2017 Feb;20(1):4-9.[Abstract][Full Text]
9. Crisafulli S, Luxi N, Sultana J, et al. Global epidemiology of acromegaly: a systematic review and meta-analysis. Eur J Endocrinol. 2021 Jul 1;185(2):251-63.[Abstract]
10. Trivellin G, Daly AF, Faucz FR, et al. Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation. N Engl J Med. 2014;371:2363-2374.[Abstract][Full Text]
11. Nachtigall L, Delgado A, Swearingen B, et al. Changing patterns in diagnosis and therapy of acromegaly over two decades. J Clin Endocrinol Metab. 2008 Jun;93(6):2035-41.[Abstract][Full Text]
12. Katznelson L, Laws ER Jr, Melmed S, et al; Endocrine Society. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014 Nov;99(11):3933-51.[Abstract][Full Text]
13. Giustina A, Barkhoudarian G, Beckers A, et al. Multidisciplinary management of acromegaly: a consensus. Rev Endocr Metab Disord. 2020 Dec;21(4):667-78.[Abstract]
14. Muhammad A, Neggers SJ, van der Lely AJ. Pregnancy and acromegaly. Pituitary. 2017 Feb;20(1):179-84.[Abstract][Full Text]
15. Ribeiro-Oliveira A Jr, Faje AT, Barkan AL. Limited utility of oral glucose tolerance test in biochemically active acromegaly. Eur J Endocrinol. 2011 Jan;164(1):17-22.[Abstract][Full Text]
16. Fleseriu M, Hashim IA, Karavitaki N, et al. Hormonal replacement in hypopituitarism in adults: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016 Nov;101(11):3888-921.[Abstract][Full Text]
17. Fleseriu M, Bodach ME, Tumialan LM, et al. Congress of Neurological Surgeons systematic review and evidence-based guideline for pretreatment endocrine evaluation of patients with nonfunctioning pituitary adenomas. Neurosurgery. 2016 Oct;79(4):E527-9.[Abstract][Full Text]
18. Freda PU, Beckers AM, Katznelson L, et al; Endocrine Society. Pituitary incidentaloma: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Apr;96(4):894-904.[Abstract][Full Text]
19. Hofman MS, Kong G, Neels OC, et al. High management impact of Ga-68 DOTATATE (GaTate) PET/CT for imaging neuroendocrine and other somatostatin expressing tumours. J Med Imaging Radiat Oncol. 2012 Feb;56(1):40-7.[Abstract]
20. Scangas GA, Laws ER Jr. Pituitary incidentalomas. Pituitary. 2014 Oct;17(5):486-91.[Abstract]
21. D'Arcy R, Courtney CH, Graham U, et al. Twenty-four-hour growth hormone profiling in the assessment of acromegaly. Endocrinol Diabetes Metab. 2017 Dec 27;1(1):e00007.[Abstract][Full Text]
22. Serioli S, Doglietto F, Fiorindi A, et al. Pituitary adenomas and invasiveness from anatomo-surgical, radiological, and histological perspectives: a systematic literature review. Cancers (Basel). 2019 Dec 4;11(12):1936.[Abstract][Full Text]
23. Knosp E, Steiner E, Kitz K, et al. Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery. 1993 Oct;33(4):610-7; discussion 617-8.[Abstract]
24. American College of Radiology. ACR appropriateness criteria: neuroendocrine imaging. 2018 [internet publication].[Full Text]
25. Fleseriu M, Biller BMK, Freda PU, et al. A Pituitary Society update to acromegaly management guidelines. Pituitary. 2021 Feb;24(1):1-13.[Abstract][Full Text]
26. Thomas M, Berni E, Jenkins-Jones S, et al. Insulin-like growth factor-1, growth hormone and disease outcomes in acromegaly: A population study. Clin Endocrinol (Oxf). 2021 Jul;95(1):143-52.[Abstract][Full Text]
27. Giustina A, Barkan A, Beckers A, et al. A consensus on the diagnosis and treatment of acromegaly comorbidities: an update. J Clin Endocrinol Metab. 2020 Apr 1;105(4):dgz096.[Abstract]
28. Melmed S, Kaiser UB, Lopes MB, et al. Clinical biology of the pituitary adenoma. Endocr Rev. 2022 Nov 25;43(6):1003-37.[Abstract][Full Text]
29. Kim J, Hong N, Choi J, et al. Sex differences in mortality in patients with acromegaly: a nationwide cohort study in Korea. Eur J Endocrinol. 2023 Aug 2;189(2):225-34.[Abstract]
30. Asa SL, Ezzat S. An update on pituitary neuroendocrine tumors leading to acromegaly and gigantism. J Clin Med. 2021 May 22;10(11):2254.[Abstract][Full Text]
31. Fahlbusch R, Kleinberg D, Biller B, et al. Surgical debulking of pituitary adenomas improves responsiveness to octreotide lar in the treatment of acromegaly. Pituitary. 2017 Dec;20(6):668-75.[Abstract]
32. Gadelha MR, Wildemberg LE, Kasuki L. The future of somatostatin receptor ligands in acromegaly. J Clin Endocrinol Metab. 2022 Jan 18;107(2):297-308.[Abstract][Full Text]
33. Fleseriu M, Zhang Z, Hanman K, et al. A systematic literature review to evaluate extended dosing intervals in the pharmacological management of acromegaly. Pituitary. 2023 Feb;26(1):9-41.[Abstract][Full Text]
34. Samson SL, Nachtigall LB, Fleseriu M, et al. Maintenance of acromegaly control in patients switching from injectable somatostatin receptor ligands to oral octreotide. J Clin Endocrinol Metab. 2020 Oct 1;105(10):e3785-e97.[Abstract][Full Text]
35. Fleseriu M, Molitch M, Dreval A, et al. MPOWERED trial open-label extension: long-term efficacy and safety data for oral octreotide capsules in acromegaly. J Clin Endocrinol Metab. 2023 Nov 17;108(12):3214-22.[Abstract][Full Text]
36. Colao A, Bronstein MD, Freda P, et al. Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab. 2014 Mar;99(3):791-9.[Abstract][Full Text]
37. Cuevas-Ramos D, Fleseriu M. Pasireotide: a novel treatment for patients with acromegaly. Drug Des Devel Ther. 2016 Jan 11;10:227-39.[Abstract]
38. Gadelha MR, Bronstein MD, Brue T, et al; Pasireotide C2402 Study Group. Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2014 Nov;2(11):875-84.[Abstract]
39. Bronstein MD, Fleseriu M, Neggers S, et al; Pasireotide C2305 Study Group. Switching patients with acromegaly from octreotide to pasireotide improves biochemical control: crossover extension to a randomized, double-blind, phase III study. BMC Endocr Disord. 2016 Apr 2;16:16.[Abstract]
40. Schmid HA, Brue T, Colao A, et al. Effect of pasireotide on glucose- and growth hormone-related biomarkers in patients with inadequately controlled acromegaly. Endocrine. 2016 Jul;53(1):210-9.[Abstract]
41. Fleseriu M, Rusch E, Geer EB. Safety and tolerability of pasireotide long-acting release in acromegaly-results from the acromegaly, open-label, multicenter, safety monitoring program for treating patients who have a need to receive medical therapy (ACCESS) study. Endocrine. 2017 Jan;55(1):247-55.[Abstract][Full Text]
42. Ezzat S, Caspar-Bell GM, Chik CL, et al. Predictive markers for postsurgical medical management of acromegaly: a systematic review and consensus treatment guideline. Endocr Pract. 2019 Apr;25(4):379-93.[Abstract]
43. Fleseriu M, Führer-Sakel D, van der Lely AJ, et al. More than a decade of real-world experience of pegvisomant for acromegaly: ACROSTUDY. Eur J Endocrinol. 2021 Aug 27;185(4):525-38.[Abstract][Full Text]
44. Hannon MJ, Barkan AL, Drake WM. The role of radiotherapy in acromegaly. Neuroendocrinology. 2016;103(1):42-9.[Abstract][Full Text]
45. Sims-Williams HP, Rajapaksa K, Yianni J, et al. Long-term safety of gamma knife radiosurgery (SRS) for acromegaly. Pituitary. 2021 Oct;24(5):724-36.[Abstract][Full Text]
46. Gheorghiu ML. Updates in outcomes of stereotactic radiation therapy in acromegaly. Pituitary. 2017 Feb;20(1):154-68.[Abstract]
47. Alonso CE, Bunevicius A, Trifiletti DM, et al. Safety and efficacy of repeat radiosurgery for acromegaly: an international multi-institutional study. J Neurooncol. 2019 Nov;145(2):301-7.[Abstract]
48. Franck SE, Muhammad A, van der Lely AJ, et al. Combined treatment of somatostatin analogues with pegvisomant in acromegaly. Endocrine. 2016 May;52(2):206-13.[Abstract][Full Text]
49. Almeida JP, Ruiz-Treviño AS, Liang B, et al. Reoperation for growth hormone-secreting pituitary adenomas: report on an endonasal endoscopic series with a systematic review and meta-analysis of the literature. J Neurosurg. 2018 Aug;129(2):404-16.[Abstract][Full Text]
50. Stone JC, Clark J, Cuneo R, et al. Estrogen and selective estrogen receptor modulators (SERMs) for the treatment of acromegaly: a meta-analysis of published observational studies. Pituitary. 2014 Jun;17(3):284-95.[Abstract]
51. Balili I, Barkan A. Tamoxifen as a therapeutic agent in acromegaly. Pituitary. 2014 Dec;17(6):500-4.[Abstract]
52. Duarte FH, Jallad RS, Bronstein MD. Clomiphene citrate for treatment of acromegaly not controlled by conventional therapies. J Clin Endocrinol Metab. 2015 May;100(5):1863-9.[Abstract]
53. Pita-Gutierrez F, Pertega-Diaz S, Pita-Fernandez S, et al. Place of preoperative treatment of acromegaly with somatostatin analog on surgical outcome: a systematic review and meta-analysis. PLoS One. 2013 Apr 25;8(4):e61523.[Abstract][Full Text]
54. Zhang L, Wu X, Yan Y, et al. Preoperative somatostatin analogs treatment in acromegalic patients with macroadenomas. A meta-analysis. Brain Dev. 2015 Feb;37(2):181-90.[Abstract]
55. Fleseriu M, Hoffman AR, Katznelson L, et al. American Association of Clinical Endocrinologists and American College of Endocrinology disease state clinical review: management of acromegaly patients: what is the role of pre-operative medical therapy? Endocr Pract. 2015 Jun;21(6):668-73.[Abstract]
56. Gadelha MR, Gordon MB, Doknic M, et al. ACROBAT edge: safety and efficacy of switching injected SRLs to oral paltusotine in patients with acromegaly. J Clin Endocrinol Metab. 2023 Apr 13;108(5):e148-59.[Abstract][Full Text]
57. ClinicalTrials.gov. A study to evaluate the safety and efficacy of paltusotine for the treatment of acromegaly (PATHFNDR-1). ClinicalTrials.gov Identifier: NCT04837040. Sep 2023 [internet publication].[Full Text]
58. ClinicalTrials.gov. A trial to assess efficacy and safety of octreotide subcutaneous depot in patients with acromegaly. ClinicalTrials.gov Identifier: NCT04076462. Jun 2023 [internet publication].[Full Text]
59. ClinicalTrials.gov. A trial to assess the long-term safety of octreotide subcutaneous depot in patients with acromegaly. ClinicalTrials.gov Identifier: NCT04125836. Aug 2023 [internet publication].[Full Text]
60. van der Lely AJ, Gomez R, Pleil A, et al. Development of ACRODAT®, a new software medical device to assess disease activity in patients with acromegaly. Pituitary. 2017 Dec;20(6):692-701.[Abstract][Full Text]
61. Giustina A, Bevan JS, Bronstein MD, et al. SAGIT®: clinician-reported outcome instrument for managing acromegaly in clinical practice--development and results from a pilot study. Pituitary. 2016 Feb;19(1):39-49.[Abstract][Full Text]
62. Kreitschmann-Andermahr I, Buchfelder M, Kleist B, et al. Predictors of quality of life in 165 patients with acromegaly: results from a single-center study. Endocr Pract. 2017 Jan;23(1):79-88.[Abstract]
63. Geraedts VJ, Andela CD, Stalla GK, et al. Predictors of quality of life in acromegaly: no consensus on biochemical parameters. Front Endocrinol (Lausanne). 2017 Mar 3;8:40.[Abstract][Full Text]
64. Kimball A, Dichtel LE, Yuen KCJ, et al. Quality of life after long-term biochemical control of acromegaly. Pituitary. 2022 Jun;25(3):531-9.[Abstract][Full Text]
65. Broersen LHA, Zamanipoor Najafabadi AH, Pereira AM, et al. Improvement in symptoms and health-related quality of life in acromegaly patients: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2021 Jan 23;106(2):577-87.[Abstract][Full Text]
66. Carmichael JD, Bonert VS, Nuño M, et al. Acromegaly clinical trial methodology impact on reported biochemical efficacy rates of somatostatin receptor ligand treatments: a meta-analysis. J Clin Endocrinol Metab. 2014 May;99(5):1825-33.[Abstract][Full Text]
67. Potorac I, Petrossians P, Daly AF, et al. T2-weighted MRI signal predicts hormone and tumor responses to somatostatin analogs in acromegaly. Endocr Relat Cancer. 2016 Nov;23(11):871-81.[Abstract]
68. Muhammad A, van der Lely AJ, Delhanty PJD, et al. Efficacy and safety of switching to pasireotide in patients with acromegaly controlled with pegvisomant and first-generation somatostatin analogues (PAPE study). J Clin Endocrinol Metab. 2018 Feb 1;103(2):586-95.[Abstract]
69. Donoho DA, Bose N, Zada G, et al. Management of aggressive growth hormone secreting pituitary adenomas. Pituitary. 2017 Feb;20(1):169-78.[Abstract]
70. Melmed S, Bronstein MD, Chanson P, et al. A consensus statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol. 2018 Sep;14(9):552-61.[Abstract][Full Text]
71. Fleseriu M, Barkan A, Del Pilar Schneider M, et al. Prevalence of comorbidities and concomitant medication use in acromegaly: analysis of real-world data from the United States. Pituitary. 2022 Apr;25(2):296-307.[Abstract][Full Text]
72. 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 May;92(5):1743-7.[Abstract][Full Text]
73. Kasuki L, Maia B, Gadelha MR. Acromegaly and colorectal neoplasm: an update. Front Endocrinol (Lausanne). 2022 Jun 20;13:924952.[Abstract][Full Text]