In 98 percent of cases, the overproduction of GH is caused by a pituitary adenoma. The rate of GH production and the aggressiveness of the tumour vary from patient to patient. Generally, more aggressive tumours are seen in younger patients.

Most pituitary adenomas occur spontaneously and are not genetically inherited. A genetic mutation in a single pituitary cell is the cause of many pituitary adenomas. This mutation, which is not present at birth but is acquired during life, occurs in a gene that regulates the transmission of chemical signals within pituitary cells, resulting in increased cell division and tumour formation.

Other rare causes of acromegaly include tumours of the pancreas, lungs, and adrenal glands. These tumours either produce GH themselves or, more frequently, they produce growth hormone-releasing hormone (GHRH), which stimulates the pituitary to make growth hormone, resulting in excessive levels of GH. In patients with these types of tumours, elevated levels of GHRH can be detected in the blood, ruling out pituitary defects as the cause of acromegaly.

It is important to note that the pituitary gland may still be enlarged in patients with GHRH-producing, non-pituitary tumours, and this enlargement may be mistaken for a tumour. Careful analysis of all pituitary tumours removed from patients with acromegaly is important so that a tumour elsewhere in the body is not overlooked.

Several rare hereditary syndromes also may cause acromegaly:

• McCune-Albright syndrome
• Multiple endocrine neoplasia (MEN) type 1
• Familial acromegaly
• Carney syndrome