Management of acromegaly: Is there a role for primary medical therapy?

Abstract

Acromegaly is a chronic, debilitating disease caused by chronic growth hormone (GH) hypersecretion which results in chronic medical comorbidities, poor quality of life and high mortality rates. Successful treatment can improve clinical signs and symptoms and normalize mortality rates. Over 95% of acromegaly is caused by a somatotroph adenoma of the pituitary, and the first-line treatment is generally transsphenoidal surgery, which can be curative in 50-60% of patients. Nonetheless, high rates of persistent acromegaly following surgery and the limited efficacy of radiation therapy necessitate chronic medical treatment for many patients. Somatostatin analogues have become the preferred first-line medical therapy for many practitioners, as they achieve better biochemical and direct tumor control than the dopamine agonists, and long-acting preparations make once monthly administration possible. Cabergoline, a dopamine agonist, offers a lower-cost option and may be effective in patients with a pituitary tumor that co-secretes GH and prolactin. Pegvisomant is a GH receptor antagonist that produces exceptional biochemical response rates but lacks any direct effects on the tumor, which may limit its effectiveness as life-long monotherapy. Combinations of these three drug classes have not been rigorously studied, and preliminary trials do not suggest improved clinical outcomes. While medical treatment options for acromegaly have significantly improved over the last 30 years, limitations remain, and a multi-specialty team approach is necessary for the effective long-term management of patients with acromegaly.