Role of Medical Therapy in the Management of Acromegaly

Abstract

Medical therapy plays an important role in the management of patients with acromegaly and is commonly used adjunctively after surgical resection of the pituitary tumor. Generally, surgery alone provides a 50 to 70% rate of cure; however, the outcome depends on the experience and ability of the surgeon and the characteristics of the tumor. The role of postsurgical medical therapy is to achieve long-term biochemical control of the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis. In some patients, medical therapies may be implemented sooner as primary or preoperative therapy. Somatostatin analogs have been the mainstay of medical therapy for acromegaly. The somatostatin analog octreotide produces normalization of IGF-I in approximately 50% of patients but is associated with gastrointestinal adverse effects, including the development of gallstones. Octreotide requires thrice-daily subcutaneous administration. Long-acting formulations of somatostatin analogs (octreotide LAR, lanreotide) are at least as effective and as well tolerated as short-acting octreotide. Unfortunately, some patients are suboptimally responsive to or become intolerant of these agents. Pegvisomant belongs to a new class of agents known as GH-receptor antagonists. This novel agent competitively binds to the GH receptor, blocking IGF-I production. Pegvisomant is highly effective in achieving normal IGF-I concentrations and in reducing signs and symptoms of acromegaly, even in patients resistant to previous treatments. Pegvisomant has been proved safe and well tolerated and has no effect on gallbladder motility. GH levels remain elevated. Transient elevations in liver enzyme levels require monitoring but rarely necessitate termination of therapy. Normalizing IGF-I concentrations with pegvisomant also may have a beneficial effect on carbohydrate metabolism and cardiovascular risk.