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Current Opinion in Endocrinology & Diabetes:
Neuroendocrinology

Pegvisomant: the role of a growth hormone receptor antagonist in the treatment of acromegaly

Ben-Shlomo, Anata; Vivien, Herman-Bonertb; Melmed, Shlomoa

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Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

© 2004 Lippincott Williams & Wilkins, Inc.

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