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.