Acromegaly

Medical Therapy

The new AACE guidelines (PDF 93KB) note that major progress has been made in developing pharmacologic agents for acromegaly, which has facilitated more aggressive management of the disease (1). They then review the major classes of pharmacologic therapy available today.

Somatostatin Analogues

Somatostatin analogues, derived from the naturally occurring inhibitory hormone, somatostatin, represent a physiologically based approach to managing acromegaly (1). These analogues act at the site of the tumor to control GH hypersecretion. Octreotide acetate, the only FDA-approved somatostatin analogue, controls GH levels in 50% to 70% of patients, and IGF-1 levels are normalized in 41% to 67% of patients (1, 2). The guidelines conclude that somatostatin analogues are first-line therapy when medical treatment of acromegaly is required.

GH receptor Antagonists

The GH receptor antagonist pegvisomant blocks GH action peripherally by competing with the natural GH molecule for binding at the GH receptor (1). Normalized IGF-1 is achieved in more than 90% of patients.(3) The guidelines conclude that pegvisomant should be used in patients for whom surgical treatment, somatostatin analogues, and dopamine agonists have proved ineffective or for those who are intolerant to somatostatin analogues or for those who have extremely high IGF-1 levels (>900 ng/mL).

Dopamine Agonists

Dopamine agonists such as bromocriptine or cabergoline bind pituitary dopamine-2 (D2) receptors and suppress GH secretion in some patients (4). One study suggests that with the newer agent, cabergoline, IGF-1 control can be achieved in about 1/3 of patients (1). Clinical response to dopamine agonist therapy varies, with prolactin-secreting tumors showing a more favorable response. The AACE guidelines conclude that dopamine agonists are far less effective than somatostatin analogues or GH receptor antagonists. They may be most useful in patients with acromegaly and hyperprolactinemia, or in those with relatively minimal elevations of IGF-1.