Acromegaly is associated with significant morbidities and a 2- to 3-fold increase in mortality because of the excessive metabolic action of GH and
IGF-I, a marker of GH output. Reductions in morbidity correspond with decreases in
IGF-I, and mortality is lowered following normalization of
IGF-I or GH levels. Therefore, this has become an important end point. Current guidelines for the treatment of
acromegaly have not considered recent advances in medical
therapy, in particular, the place of
pegvisomant, a GH receptor antagonist. Treatment goals include normalizing
biochemical markers, controlling
tumor mass, preserving pituitary function, and relieving signs and symptoms. Surgery reduces
tumor volume and is considered first-line
therapy. Radiation reduces
tumor volume and GH and
IGF-I levels, but the onset of action is slow and
hypopituitarism typically develops. Therefore,
pharmacotherapy is often used following surgery or as first-line
therapy for nonresectable
tumors.
Dopamine agonists can be considered in patients exhibiting minimal disease or those with GH-
prolactin-cosecreting
tumors but will not achieve
hormone normalization in most patients.
Somatostatin analogs effectively suppress GH and
IGF-I in most patients, but intolerance (e.g.
diarrhea, cramping,
gallstones) can occur.
Pegvisomant, the newest therapeutic option, blocks GH action at peripheral receptors, normalizes
IGF-I levels, reduces signs and symptoms, and corrects metabolic defects.
Pegvisomant does not appear to affect
tumor size and has few adverse effects.
Pegvisomant is the most effective
drug treatment for
acromegaly in normalizing
IGF-I and producing a clinical response; it is the preferred agent in patients resistant to or intolerant of
somatostatin analogs.