Keith E. Friend, MD


Cancer Control. 2002;9(3) 

In This Article

Abstract and Introduction

Background: The treatment of acromegaly can be challenging. Despite a multimodality approach (surgery, radiation, dopamine agonists, somatostatin analogs), many patients do not achieve normalization of serum insulin-like growth factor I (IGF-I) concentrations.
Methods: The author discusses the characteristics and indications of pegvisomant therapy for patients with acromegaly and compares the use of this newly developed GH receptor antagonist with other pharmacological agents such as somatostatin and dopamine agonists.
Results: Therapy with pegvisomant allows serum IGF-I concentrations to be normalized in up to 97% of patients with acromegaly, including those who have failed other treatment modalities. With this agent, circulating GH levels increase as a result of the drop in IGF-I levels. The rise is rapid (within 2 weeks) and does not appear to be progressive over time.
Conclusions: Published studies have shown pegvisomant to have efficacy in the treatment of acromegaly. As it appears to be well tolerated and safe, this novel compound may be an important therapeutic option for patients with acromegaly. Additional study of this novel agent and its mode of action is warranted.

Acromegaly is a relatively rare disease caused by the hypersecretion of growth hormone (GH). It almost always occurs as a result of a benign adenoma in the anterior portion of the pituitary gland. Patients with acromegaly have been reported to have an increased morbidity and mortality when compared with the general population.[1,2,3,4] The clinical manifestations of uncontrolled acromegaly include soft-tissue swelling, joint pain, nerve entrapment, glucose intolerance, hypertension, and cardiac disease.[5,6,7]

The primary biochemical goal of acromegaly treatment is to restore the GH/IGF-I axis to normal. Because GH release is highly pulsatile, serum concentrations vary throughout the day. Thus, the use of random serum GH concentrations is not reliable to determine if acromegaly is present or adequately controlled. However, the GH-stimulated peptide insulin-like growth factor-I (IGF-I) is present in the serum in more steady concentrations. IGF-I represents an excellent integrative marker of total GH secretion and should therefore be used as the primary biomarker of acromegaly control. In adequately controlled patients, IGF-I levels should fall into the normal age-and gender-adjusted normal range.