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Acromegaly

A rare condition that occurs when the pituitary gland produces excess growth hormone, often leading to abnormal growth of bones and tissues.1

A hormonal disorder that causes noticeable physical changes

Acromegaly is a rare and progressive endocrine disorder characterized by the dysregulation of growth hormone (GH) secretion, resulting in the overproduction of insulin-like growth factor 1 (IGF-1).1-3 It is often referred to as somatotroph adenoma or growth hormone excess, given the presence of too much growth hormone.4

Acromegaly is differentiated from gigantism depending on whether excess GH production occurs before (gigantism) or after (acromegaly) growth plates are fused.1

Causes of acromegaly, the release of excess GH, can be divided into:1,3

Primary GH excess
  • Somatrotroph GH-secreting adenoma of the pituitary gland (most common)
  • Pituitary adenomas that secrete multiple hormones and GH-cell carcinomas
Ectopic or Iatrogenic 
GH excess
  • Ectopic GH excess – GH is produced outside the pituitary gland or in an abnormal location by other tumors such as lymphoma and pancreatic-islet cell tumors
  • Iatrogenic GH excess – GH is produced due to excessive GH administration (medical intervention or treatment)
Excess growth hormone-releasing hormone (GHRH)
  • Not as common, acromegaly is caused by excess GHRH as a result of hypothalamic or ectopic tumors

Prevalence

It is estimated that acromegaly has an incidence of 4 per million, per year,2 with an increased incidence of mortality compared to the general population.2,5 There are approximately 25,000 patients afflicted with acromegaly in the United States.6

Onset is usually in the third or fourth decade of life, with a mean age ranging between 40 (for men) and 45 (for women) years.1,3

Despite its relatively small incidence, this rare disorder can be treated using various treatment modalities.

Etiology

Acromegaly is mainly caused by a benign somatotroph GH-secreting adenoma of the anterior pituitary gland.7 However, there are rare instances in which malignant pituitary tumors are present. Other etiologies include hypothalamic and ectopic neuroendocrine tumors that stimulate pituitary somatotrophs, inducing excess secretion of GH.3

The result of dysregulated GH secretion has a causal effect on the overproduction of IGF-1 leading to physical deformities and systemic burden in people with acromegaly.7 GH is responsible for physical growth; too much of this hormone causes bones, cartilage, body organs, and other tissues to grow disproportionately large.8

Excess GH and IGF-1 lead to a biochemical imbalance and the clinical manifestations of acromegaly, usually due to a benign somatotrophic pituitary adenoma4, 13, 14

somatic-growth

Cardiovascular Focus:
Acromegaly has been associated with an increased incidence of cardiovascular disease. Given this increase, it is critical to initiate treatment to minimize cardiovascular risk.9 There is a breadth of data to suggest disease control of acromegaly reduces the likelihood of the development of coronary heart disease.10

Diabetes Focus:
Diabetes mellitus is a frequent complication of acromegaly with a prevalence of 12-37%.11 Both GH and IGF-1 play an important role in glucose regulation.12

Chronic excess of GH impacts:12

  • Insulin sensitivity
  • Increases gluconeogenesis
  • Reduces glucose uptake into cells
  • Alters pancreatic ß cell function

As a result of the complications arising from chronic excess of GH, alterations in glucose metabolism are commonly associated with acromegaly. Hence, the increased cardiovascular risk and mortality.12

Identification Diagnosis

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REFERENCES: 1. Adigun OO, Nguyen M, Fox TJ, et al. Acromegaly. [Updated 2023 Feb 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431086/. 2. Dekkers OM, Biermasz NR, Pereira AM et al. Mortality in acromegaly: a metaanalysis. J Clin Endocrinol Metab. 2008;93: 61–67. doi: 10.1210/jc.2007-1191. 3. Ogedegbe OJ, Cheema AY, Khan MA, et al. A Comprehensive Review of Four Clinical Practice Guidelines of Acromegaly. Cureus. 2022;Sep 3;14(9):e28722. doi: 10.7759/cureus.28722. 4. Christofides EA. Clinical importance of achieving biochemical control with medical therapy in adult patients with acromegaly. Patient Prefer Adherence. 2016 Jul 13;10:1217-25. doi: 10.2147/PPA.S102302. 5. Kauppinen-Makelin R, Sane T, Reunanen A, et al. A nationwide survey of mortality in acromegaly. J Clin Endocrinol Metab. 2005;90:4081–4086. doi: 10.1210/jc.2004-1381. 6. Broder MS, Chang E, Cherepanov D, Neary MP, Ludlam WH. Incidence and prevalence of acromegaly in the United States: a claims-based analysis. Endocr Pract. 2016 Nov;22(11):1327-1335. doi: 10.4158/EP161397.OR. 7. Daniel CP, Wagner MJ, Borne GE, et al. Acromegaly: Pathophysiological Considerations and Treatment Options Including the Evolving Role of Oral Somatostatin Analogs. Pathophysiology. 2023 Sep 1;30(3):377-388. doi: 10.3390/pathophysiology30030029. 8. Acromegaly. National Institute of Diabetes and Digestive and Kidney Diseases. Last updated January 2020. Accessed February 10, 2024. https://www.niddk.nih.gov/health-information/endocrine-diseases/acromegaly. 9. Fukuda I, Hizuka N, Muraoka T, et al. Clinical features and therapeutic outcomes of acromegaly during the recent 10 years in a single institution in Japan. Pituitary. 2014 Feb;17(1):90-5. doi: 10.1007/s11102-013-0472-6. 
10. Berg C, Petersenn S, Lahner H, et al. Investigative Group of the Heinz Nixdorf Recall Study and the German Pegvisomant Observational Study Board and Investigators. Cardiovascular risk factors in patients with uncontrolled and long-term acromegaly: comparison with matched data from the general population and the effect of disease control. J Clin Endocrinol Metab. 2010 Aug;95(8):3648-56. doi: 10.1210/jc.2009-2570. 11. Hannon AM, Thompson CJ, Sherlock M. Diabetes in Patients With Acromegaly. Curr Diab Rep. 2017 Feb;17(2):8. doi: 10.1007/s11892-017-0838-7. 12. Ferraù F, Albani A, Ciresi A, Giordano C, Cannavò S. Diabetes Secondary to Acromegaly: Physiopathology, Clinical Features and Effects of Treatment. Front Endocrinol (Lausanne). 2018 Jul 6;9:358. doi: 10.3389/fendo.2018.00358. 13. Carmichael JD, Bonert VS, Nuño, M, Ly D, Melmed S. Acromegaly clinical trial methodology impact on reported biochemical efficacy rates of somatostatin receptor ligand treatments: a meta-analysis. J Clin Endocrinol Metab. 2014;99(5):1825-1833. 14. Carroll PV, Jenkins PJ. Acromegaly. In: Feingold KR, Anawalt B, Boyce A, et al, eds. Endotext [Internet]. South Dartmouth, MA: MDText.com, Inc.; 2016.