• Clinical science

Acromegaly

Summary

Acromegaly is a condition in which benign pituitary adenomas lead to an excess secretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). In adults, whose epiphyseal plates are closed, the disease causes enlarged hands and feet, coarsened facial features, and pathological growth of internal organs. If the condition occurs in children, before epiphyseal plate closure, it is known as gigantism, which is discussed in a separate article. The first step in diagnosing acromegaly is to measure IGF-1 levels. Further testing includes an oral glucose tolerance test (OGTT) with assessment of GH levels, and evaluation of pituitary tumors via cranial MRI. Management consists of transsphenoidal adenomectomy for operable tumors, or GH-inhibiting medication and radiotherapy if surgery is contraindicated or unsuccessful. Adequate treatment is vital to reduce the risk of complications, such as cardiovascular disease and cerebral aneurysms, as these may considerably increase mortality.

Epidemiology

  • Prevalence: 1–9/100,000 in the US [1]
  • Age of onset: 3rd decade of life (mean age at diagnosis usually 40–45 years) [1]
  • Sex: = [1]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Pathophysiology

Excess GH secretion before the conclusion of longitudinal growth (i.e., prior to epiphyseal plate closure) leads to pituitary gigantism with a possible height of ≥ 2 m. After epiphyseal plate closure, GH excess causes acromegaly, but no change in height!

Clinical features

Consider acromegaly in patients who report having had to increase hat, shoe, glove, and ring sizes in the past!

Diagnostics

  • Hormone analysis [5][6]
    • Serum IGF-1 concentration: the best single test
    • OGTT with baseline GH and measure GH after 2 hours: the most specific test
      • If GH suppressed: acromegaly ruled out
      • If GH not suppressed: confirmed acromegaly; conduct pituitary MRI to determine the source of excess GH
  • Pituitary MRI [5][6]
    • Imaging modality of choice
    • Usually shows a visible mass: confirmed GH-secreting pituitary adenoma
    • If normal: screen for an extrapituitary cause (e.g., CT scan of the chest and abdomen, measure GHRH)

Differential diagnoses

The differential diagnoses listed here are not exhaustive.

Treatment

Transsphenoidal adenomectomy is the method of choice for treating acromegaly. In patients with inoperable tumors or unsuccessful surgery, medication and radiotherapy are indicated to reduce tumor size and limit the effects of GH and IGF-1. [5][6]

Danger of hypopituitarism following surgery or radiotherapy!

Complications

Complications lead to increased mortality. [8]

We list the most important complications. The selection is not exhaustive.

  • 1. Broder MS, Chang E, Cherepanov D, Neary MP, Ludlam WH. INCIDENCE AND PREVALENCE OF ACROMEGALY IN THE UNITED STATES: A CLAIMS-BASED ANALYSIS. Endocrine Practice. 2016; 22(11): pp. 1327–1335. doi: 10.4158/ep161397.or.
  • 2. Katznelson L, Laws ER, Melmed S, et al. Acromegaly: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism. 2014; 99(11): pp. 3933–3951. doi: 10.1210/jc.2014-2700.
  • 3. Ghazi AA, Amirbaigloo A, Dezfooli AA, et al. Ectopic acromegaly due to growth hormone releasing hormone. Endocrine. 2012; 43(2): pp. 293–302. doi: 10.1007/s12020-012-9790-0.
  • 4. Hasan W, Cowen T, Barnett PS, Elliot E, Coskeran P, Bouloux PM. The sweating apparatus in growth hormone deficiency following treatment with r-hGH and in acromegaly. Auton Neurosci. 2001; 89(1-2): pp. 100–109. doi: 10.1016/S1566-0702(01)00257-0.
  • 5. Katznelson L, Atkinson J, Cook D, Ezzat S, Hamrahian A, Miller K. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Acromegaly-2011 Update. Endocrine Practice. 2011; 17(Supplement 4): pp. 1–44. doi: 10.4158/ep.17.s4.1.
  • 6. Melmed S, Bronstein MD, Chanson P, et al. A Consensus Statement on acromegaly therapeutic outcomes. Nature Reviews Endocrinology. 2018; 14(9): pp. 552–561. doi: 10.1038/s41574-018-0058-5.
  • 7. Rowland NC, Aghi MK. Radiation treatment strategies for acromegaly. Neurosurg Focus. 2010; 29(4): p. E12. doi: 10.3171/2010.7.FOCUS10124.
  • 8. Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev. 2004; 25(1): pp. 102–152. doi: 10.1210/er.2002-0022.
  • 9. Capatina C, Wass JA. 60 Years of Neuroendocrinology: Acromegaly. J Endocrinol. 2015; 226(2): pp. T141–160. doi: 10.1530/JOE-15-0109.
  • 10. Dworakowska D, Grossman AB. Colonic Cancer and Acromegaly. Frontiers in Endocrinology. 2019; 10. doi: 10.3389/fendo.2019.00390.
last updated 10/20/2020
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