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Causes and clinical manifestations of acromegaly

Shlomo Melmed, MD
Section Editor
Peter J Snyder, MD
Deputy Editor
Kathryn A Martin, MD


Acromegaly is the clinical syndrome that results from excessive secretion of growth hormone (GH) [1]. Its annual incidence is six per million people [2]. The mean age at diagnosis is 40 to 45 years.

The causes and clinical features of acromegaly will be reviewed here. The laboratory diagnosis and treatment of acromegaly are discussed separately. (See "Diagnosis of acromegaly" and "Treatment of acromegaly".)


The most common cause of acromegaly is a somatotroph (growth hormone [GH]-secreting) adenoma of the anterior pituitary. These adenomas account for about one-third of all hormone-secreting pituitary adenomas (table 1). GH excess that occurs before fusion of the epiphyseal growth plates in a child or adolescent is called pituitary gigantism. (See "Pituitary gigantism".)

An activating mutation of the alpha subunit of the guanine nucleotide stimulatory protein (Gs-alpha) gene is found in approximately 40 percent of somatotroph adenomas [3-5]. These mutations result in constitutive activation of adenylyl cyclase, which may play a role in both cell division in and excessive GH secretion by these adenomas.

The pituitary tumor transforming gene is also overexpressed in most human somatotroph adenomas [6]. It also appears to play a role in tumor invasiveness, since expression is increased in tumors that invade the sphenoid bone.

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Literature review current through: Sep 2017. | This topic last updated: Oct 14, 2015.
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