15th September 2024

Acromegaly

Acromegaly is a disorder characterised by excessive secretion of growth hormone (GH), leading to increased hepatic production of insulin-like growth factor 1 (IGF-1). Most cases are diagnosed from 40 to 60 and are caused by anterior pituitary adenomas, which include both macroadenomas (>1 cm) and microadenomas (<1 cm). Hereditary conditions such as multiple endocrine neoplasia type 1, which involves hyperplasia of endocrine organs, and McCune-Albright syndrome, characterised by autonomous endocrine function, can lead to acromegaly. Additionally, other iatrogenic tumours, including lymphoma and pancreatic islet cell tumours, can result in excess GH production. When GH excess occurs before the end of puberty, while the epiphyseal growth plates are still open, the condition is termed gigantism.

Clinical features

There are a wide range of features caused by excess GH and the direct effects of adenoma. The onset tends to be slow, taking years to manifest. Below is a concise summary of the main features and complications.

Investigations

An oral glucose tolerance test (OGTT) is used to confirm the diagnosis. This test involves administering a 75 g oral glucose load, which should suppress GH in normal individuals. IGF-1 levels are used as a screening test and can aid in the diagnosis. IGF-1 is preferred over GH due to its lower variability.

If the blood tests confirm elevated GH levels through the OGTT, an MRI is the preferred imaging method for detecting a pituitary tumour. If no adenoma is identified, cross-sectional imaging of the body should be conducted to identify an ectopic source.

Additionally, pituitary function tests should be performed as acromegaly may affect other pituitary hormones and formal visual testing to assess the extent of the visual field defect. Echocardiogram, sleep studies and isotope bone scans should be considered as acromegaly has many systemic complications.

Management

Transsphenoidal surgery is typically the first line treatment option in micro and macroadenomas.  If levels of these hormones are still too high or begin to rise again, further treatment with radiotherapy and medications is required.

The three main types of medications used are the following:

• Somatostatin analogues (octreotide, lanreotide)
• Dopamine agonists (bromocriptine)
• Growth hormone-receptor antagonists (pegvisomant)

Post-operative complications of transsphenoidal surgery include vasopressin deficiency, which occurs in the first few days, and SIADH, which tends to occur after a week and is mostly transient.

References

• Melmed S, Katznelson L. UpToDate [Internet]. Snyder P, Martin K, editors. UpToDate. 2024. Available from: https://www.uptodate.com/contents/causes-and-clinical-manifestations-of-acromegaly#references