Acromegaly: Medical Management

Abstract

In recent years, significant advances in the pharmacological options for therapy of acromegaly have been made and thus medical management has a major role in the care of patients with this disease. Disease-specific medical therapies are directed at controlling the excessive hormone secretion i.e. normalizing serum levels of GH and IGF-I. These medical therapies are used predominantly after surgical therapy that was not curative, in some cases also after radiotherapy and in others as primary therapy. Three classes of medication are now available; dopamine agonists, somatostatin analogs and a GH receptor antagonist, pegvisomant. These medications work at different targets along the GH-IGF-I axis and thus treat acromegaly by different mechanisms. Dopamine agonists inhibit pituitary GH secretion by unclear mechanisms, somatostatin analogs activate somatostatin receptors that suppress tumoral GH secretion with the subsequent fall in serum IGF-I levels and pegvisomant blocks peripheral GH action leading to the fall in IGF-I levels. Dopamine agonists are orally active, but have a low rate of success and do not produce significant tumor shrinkage in patients with acromegaly. The clinically available long acting somatostatin analogs, octreotide LAR and lanreotide autogel, comparably normalize IGF-I levels in LIP to two-thirds of patients. The extent of biochemical control achieved with somatostatin analogs is similar when used as adjunctive or primary therapy. Signs and symptoms of acromegaly and other clinical sequelae of the disease generally improve with somatostatin analog therapy, but their effects on glucose tolerance and insulin resistance are variable. Long-acting somatostatin analog use is can be associated with tumor shrinkage, which is greater when they are given as primary therapy. Gastrointestinal complaints are the most common side effects of somatostatin analogs, but do not typically limit their clinical use. Pegvisomant, the GH receptor antagonist, was found, in clinical trials, to normalize IGF-I levels in nearly all patients. Pegvisomant therapy improves the signs and symptoms of acromegaly, reduces insulin resistance and lowers insulin and/or oral agent requirements in patients with diabetes. Liver enzyme elevations, which occur in a small percentage of patients, need to be monitored for, but only rarely limit therapy. In general, tumor size does not change on pegvisomant therapy, but it does not reduce their size and 2-3\% of tumors continue to grow while on this therapy. Treatment of acromegaly often requires use of multiple modalities in order to achieve adequate control of the disease. The approach to medical therapy should be individualized considering disease severity, symptoms, tumor size and location, co-morbid conditions and patient preferences. Recent advances in the options for medical management of acromegaly have now made disease control achievable in all patients with acromegaly.