PatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.
Growth hormone (GH) stimulates the production of insulin-like growth factor 1 (IGF-1), which is produced in the liver and many other tissues. IGF-1 is the main mediator of the actions of GH.
- Acromegaly is usually caused by excessive secretion of GH by a pituitary tumour (macroadenoma or microadenoma).
- Other rare causes include increased GH-releasing hormone (GHRH) from hypothalamic tumours, and ectopic GHRH or GH from non-endocrine tumours - eg, lung cancer, cancer of the pancreas, carcinoid tumours, medullary carcinoma of the thyroid.
Acromegaly causes an overgrowth of all organ systems, bones, joints and soft tissues.
- The prevalence is estimated at 1:140,000-250,000.
- It is most often diagnosed in middle-aged adults (average age 40 years).
- Men and women are equally affected.
- Due to the insidious onset and slow progression, acromegaly is often diagnosed up to ten years and sometimes even longer after its onset.
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Often an insidious onset and symptoms may precede the diagnosis by several years.
- Due to tumour:
- Visual field defects: the most common defect is a bitemporal hemianopia.
- Due to excess of GH:
- Gradual change in appearance due to the effects on cartilage and soft tissues: enlargement of hands and feet (increase in ring and shoe size), frontal bossing, thickening of the nose, enlarged tongue (macroglossia), growth of the jaw (prognathism), and coarsening of facial features.
- Macroglossia may cause obstructive sleep apnoea leading to daytime tiredness.
- Excessive sweating and oily skin, with development of skin tags. Women may have mild hirsutism.
- Articular overgrowth of synovial tissue and arthropathy leading to arthritis (widespread osteoarthritis of the weight-bearing joints), back pain and kyphosis.
- Visceral hypertrophy - eg, heart, liver, thyroid (with a multinodular goitre), prostate and kidneys.
- Nerve compression symptoms may occur, especially carpal tunnel syndrome.
- Cardiac features include hypertension, left ventricular hypertrophy, cardiomyopathy and arrhythmias.
- Due to associated hyperprolactinaemia - eg, galactorrhoea, amenorrhoea.
- Hypopituitarism: decreased secretion of anterior pituitary hormones and compression of pituitary stalk.
See also separate article on Pituitary Function Tests.
- Visual field tests.
- Blood glucose; serum phosphate, urinary calcium and serum triglycerides may also be raised.
- Assessment of GH:
- Random GH: often not diagnostic because of episodic secretion and short half-life of the hormone.
- Glucose tolerance test: GH is normally inhibited by glucose. If the glucose load fails to suppress the GH level below 0.3 mcg/L and the IGF-1 level is elevated then the diagnosis of acromegaly can be confirmed.
- IGF-1: long half-life and so is a useful measurement to assess GH secretion and therefore screen for acromegaly and monitor the effect of therapy.
- IGF-binding protein-3 (IGFBP-3): is the main binding protein for circulating IGF and is increased in acromegaly. Can be useful in the diagnosis of acromegaly.
- GHRH concentration can be obtained if clinically indicated.
- Assessment of other pituitary hormones: prolactin, adrenal, thyroid, and gonadal hormones.
- MRI scan of pituitary and hypothalamus: more sensitive than CT scan.
- CT scan: for lung, pancreatic, adrenal or ovarian tumours that may secrete ectopic GH or GHRH.
- Total body scintigraphy with radio-labelled OctreoScan® (somatostatin) to aid localisation of the tumour.
- Cardiac assessment: electrocardiogram, echocardiogram.
Screening for colorectal cancerBecause patients with acromegaly have an increased prevalence of colorectal adenomas and cancer, it is recommended that patients with acromegaly should be offered regular colonoscopy screening, starting at the age of 40 years. The frequency of repeat colonoscopy should depend on the findings at the original screening and the activity of the underlying acromegaly:
- Patients with an adenoma at first screening or elevated serum IGF-1 level above the maximum of the age-corrected normal range should be offered three-yearly screening.
- Patients with a negative first colonoscopy or a hyperplastic polyp or normal GH/IGF-1 levels should be offered screening every 5-10 years.
See also the separate article on Screening for the Early Detection of Colorectal Cancer.
Pseudo-acromegaly is the presence of a similar physical appearance in the absence of elevated GH or IGF-1. Causes of pseudo-acromegaly include insulin resistance associated with hyperinsulinaemia and minoxidil treatment.
The aim of management is to control the symptoms caused by the local effects of the tumour and due to the excess hormone production, and to normalise hormone levels. No single treatment is completely effective in achieving these aims and so a combination of treatments is required.
- Trans-sphenoidal surgery is the treatment of choice in most cases.
- However, endoscopic trans-sphenoidal treatment for GH-secreting pituitary adenomas has shown similar outcomes for non-invasive macroadenomas compared with traditional microsurgical techniques.
- Patients with residual disease can then be offered adjuvant drug treatment.
- Patients may need drug treatment after surgery in order to reduce GH levels.
- Radiotherapy is used for refractory disease, as an adjuvant for large invasive tumours and when surgery is contra-indicated.
- Somatostatin analogues:
- Octreotide and lanreotide are analogues of the hypothalamic release-inhibiting hormone somatostatin.
- GH-secreting pituitary tumours can expand during treatment and patients should therefore be monitored for signs of tumour expansion - eg, regular assessment of visual fields.
- Dopamine agonists:
- Bromocriptine, cabergoline and quinagolide are effective but are less effective than somatostatin analogues.
- Chronic use of ergot-derived dopamine agonists is associated with a risk of fibrosis, particularly cardiac fibrosis. Cardiac valvulopathy should be excluded by echocardiography before treatment with cabergoline or bromocriptine. Patients commenced on cabergoline should be monitored for signs of cardiac fibrosis during treatment, including echocardiography within 3–6 months of starting treatment and subsequently at 6–12-month intervals. Treatment should be stopped if echocardiography shows new or worsened valvular regurgitation, valvular restriction or valve leaflet thickening.
- However dopamine agonists remain a useful adjunct in the management of acromegaly.
- Tumours that also secrete prolactin have a better response rate to dopamine agonists.
- Genetically modified analogue of human GH and is a highly selective GH receptor antagonist.
- Has been shown to normalise IGF-1 levels in 90-100% of patients.
- A long term study found that pegvisomant is an effective and safe medical treatment for patients with acromegaly.
- GH levels increase during treatment and no decrease in tumour size is seen.
- Pegvisomant is licensed for the treatment of acromegaly in patients with inadequate response to surgery, radiotherapy or somatostatin analogues.
- Hypertension, ischaemic heart disease, cardiac failure, cerebrovascular disease.
- Acromegalic arthropathy, which affects up to 70% of patients and involves both the axial and peripheral skeleton.
- Obstructive sleep apnoea.
- Increased incidence of colonic polyps and adenocarcinoma of the colon.
- Patients may develop hypopituitarism immediately after surgery, or several years after radiotherapy.
- Damage caused by the tumour may result in hyperprolactinaemia and deficiencies of glucocorticoids, sex steroids and thyroid hormone.
- Pregnancy in women with active or uncontrolled acromegaly may be associated with an increased risk of gestational diabetes and gravid hypertension.
- High levels of GH, even when the patient has no symptoms, are associated with a 2- to 3-fold increase in mortality.
- The post-treatment GH concentration is probably the best predictor of survival and life expectancy outcomes can be stratified according to the post-treatment GH concentration. If GH secretion is controlled then life expectancy merges with that of the matched general population.
- Tumour size: microadenoma (tumour less than 10 mm) is associated with a better prognosis than macroadenoma, mainly because persistence of disease after surgery is more common with macroadenomas.
- Hypertension, cardiovascular disease, diabetes and long duration of symptoms are also poor prognostic factors.
Further reading & references
- Chanson P, Salenave S; Acromegaly. Orphanet J Rare Dis. 2008 Jun 25;3:17. doi: 10.1186/1750-1172-3-17.
- Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups; British Society of Gastroenterology (May 2010 update from 2002)
- Sam AH, Tan T, Meeran K; Insulin-mediated "pseudoacromegaly". Hormones (Athens). 2011 Apr-Jun;10(2):156-61.
- Ghazi A, Khosla S, Becker K; Acromegaloid facial appearance: case report and literature review. Case Rep Endocrinol. 2013;2013:970396. doi: 10.1155/2013/970396. Epub 2013 Feb 28.
- Buchfelder M, Schlaffer S; Surgical treatment of pituitary tumours. Best Pract Res Clin Endocrinol Metab. 2009 Oct;23(5):677-92.
- Campbell PG, Kenning E, Andrews DW, et al; Outcomes after a purely endoscopic transsphenoidal resection of growth hormone-secreting pituitary adenomas. Neurosurg Focus. 2010 Oct;29(4):E5. doi: 10.3171/2010.7.FOCUS10153.
- British National Formulary
- Manjila S, Wu OC, Khan FR, et al; Pharmacological management of acromegaly: a current perspective. Neurosurg Focus. 2010 Oct;29(4):E14. doi: 10.3171/2010.7.FOCUS10168.
- Position statement on the use of dopamine agonists in endocrine disorders; Society for Endocrinology (Feb 2009 - reviewed Nov 2011)
- 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 May;97(5):1589-97. doi: 10.1210/jc.2011-2508. Epub 2012 Feb 22.
- Melmed S, Casanueva FF, Klibanski A, et al; A consensus on the diagnosis and treatment of acromegaly complications. Pituitary. 2013 Sep;16(3):294-302. doi: 10.1007/s11102-012-0420-x.
- Ayuk J, Sheppard MC; Growth hormone and its disorders. Postgrad Med J. 2006 Jan;82(963):24-30.
- Caron P, Broussaud S, Bertherat J, et al; Acromegaly and pregnancy: a retrospective multicenter study of 59 pregnancies in J Clin Endocrinol Metab. 2010 Oct;95(10):4680-7. Epub 2010 Jul 21.
- Kauppinen-Makelin R, Sane T, Reunanen A, et al; A nationwide survey of mortality in acromegaly. J Clin Endocrinol Metab. 2005 Jul;90(7):4081-6. Epub 2005 May 10.
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.
Dr Colin Tidy
Dr Colin Tidy
Dr Adrian Bonsall