Pegvisomant therapy for acromegaly

Abstract

Despite traditional, multimodality therapy that consisted of surgery, radiotherapy and medical therapies, many patients with acromegaly could not be adequately treated. Pegvisomant is a novel growth hormone receptor antagonist that became available for the treatment of acromegaly in 2003. This drug is a growth hormone variant that has nine mutations to human growth hormone. These give it high affinity for the growth hormone receptor as well as disrupting growth hormone receptor dimerization, with the net effect being antagonism of growth hormone at its receptor. Traditional methods of therapy for acromegaly treat the disease by reducing pituitary tumor secretion of growth hormone and, thus, lowering serum insulin-like growth factor-I levels. Pegvisomant, by contrast, blocks the actions of circulating growth hormone excess, but does not lower serum growth hormone levels. Its efficacy, therefore, is assessed by monitoring serum insulin-like growth factor-I levels. In clinical trials, pegvisomant has been shown to effectively normalize insulin-like growth factor-I levels in up to 97% of patients and to improve acromegaly-related signs and symptoms, and morbidities such as insulin resistance. As the action of pegvisomant does not rely on the tumor’s receptor profile, it can be effective even in patients resistant to somatostatin analog therapy. Individually tailored therapy guided by serum insulin-like growth factor-I normalization goals and improvement in clinical signs and symptoms should be undertaken while growth hormone deficiency should be avoided. Pegvisomant is very well tolerated, but liver transaminase levels need to be monitored during therapy. As pegvisomant does not shrink pituitary tumors, the underlying rate of tumor growth may continue on this therapy and periodic pituitary imaging needs to be conducted during therapy.

Keywords::

• acromegaly
• pegvisomant