Acromegaly medications (Mechanism of Action)

The indications for medical treatment of acromegaly include patients who are deemed high risk for transsphenoidal surgery, and invasive macroadenoma with parasellar extension but no mass effect. Also, patients with McCune-Albright syndrome either due to the absence of an anatomic lesion (remember, this occurs as a result of constitutive activation of the Gs alpha subunit of the GPCR) or presence of significant cranial fibrous dysplasia. Due to the high remission rates after surgery for those with microadenomas, medical therapy should not be selected as the primary treatment in this patient subset.

Somatostatin analogs

Somatostatin analogs (SSAs) are a class of drugs that bind to and activate somatostatin receptors (SSTRs). Somatostatin is a naturally occurring hormone that inhibits the secretion of growth hormone (GH) from the somatotroph cells in the pituitary gland. The use of SSAs for the treatment of acromegaly was first reported in the early 1980s. Since then, several SSAs have been developed and are now used clinically. The currently available SSAs include octreotide (octreotide short release), somatuline (lanreotide), and sandostatin (octreotide long-acting release). All three of these agents are approved by the United States Food and Drug Administration (FDA) for the treatment of acromegaly.


Pegvisomant is a relatively new medication used in the treatment of acromegaly, pegvisomant’s mechanism of action is unique in that it targets the growth hormone receptor (GHR) directly. pegvisomant structurally mimics growth hormone (GH), allowing it to bind and occupy the GH receptor pocket. This prevents GH from binding and activating the GHR, thus halting the downstream signaling cascade that leads to cell proliferation. Additionally, pegvisomant does not activate the GHR itself (termed an antagonistic action), rather it induces defective dimerization of the receptor, preventing subsequent signal transduction pathways.


Cabergoline is a dopamine agonist that has been shown to be effective in the treatment of growth hormone (GH)-secreting tumors. The mechanism by which cabergoline exerts its effects is not completely understood, but it is thought to work via the downregulation of D2 receptors. This is significant because GH-secreting tumors express D2R receptors to varying degrees, which determines their response to dopaminergic agonists. Indeed, the responsiveness of D2R’s on somatotroph tumors depends on their sensitivity and the concentration of circulating GH.


Images(s) Courtesy


Kindly Let Us Know If This Was helpful? Thank You!

About the Author MyEndoConsult

The MyEndoconsult Team. A group of physicians dedicated to endocrinology and internal medicine education.

{"email":"Email address invalid","url":"Website address invalid","required":"Required field missing"}