Acromegaly treatments do not offer complete remission in 30% of patients. Development of an innovative growth hormone receptor antagonist, pegvisomant, may offer improved disease control as it directly reduces peripheral insulinlike growth factor I synthesis.
Pegvisomant is a mutated growth hormone analogue that prevents functional dimerization of the growth hormone receptor therefore fails to elicit growth hormone -signal transduction pathways and insulinlike growth factor I synthesis and secretion. More than 90% of patients exhibit normal insulinlike growth factor I levels with pegvisomant treatment. Soft-tissue swelling, excessive perspiration, fatigue, and glucose tolerance are markedly improved. Pituitary tumors have enlarged in a few treated patients; some had liver function abnormalities, and all exhibited increased growth hormone levels. Other minor side effects included reversible injection site reactions, musculoskeletal pain, diarrhea, and nausea. Concerns regarding long-term effects include pituitary tumor size progression or development of somatotroph cell hyperplasia, which may be related to the observed increase of circulating growth hormone levels; liver function abnormalities; formation of anti–growth hormone antibodies; and development of growth hormone deficiency. Insulinlike growth factor I measurements are the only reliable monitoring system because growth hormone levels are elevated during drug treatment.
Pegvisomant is most efficacious in reducing insulinlike growth factor I levels in patients with acromegaly, and a careful controlled assessment of long-term effects is required to evaluate its place in the long-term treatment of acromegaly.
aCedars-Sinai Medical Center–UCLA School of Medicine, Los Angeles, California, USA; and bPituitary Center, Los Angeles, California, USA
Correspondence to Shlomo Melmed, MD, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Room 2015, Los Angeles, CA 90048, USA
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