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Medical Therapy for Acromegaly

Medical Therapy

Medication for acromegaly may decrease the secretion of GH and the subsequent production of IGF-1, reduce the size of the tumour, and control symptoms. Drug therapy has been used to shrink large tumours before surgery. Medical therapies include dopamine agonists, GH receptor antagonists, and somatostatin analogues.¹

Dopamine Agonists

Dopamine has a paradoxical effect on pituitary function in acromegalic patients: it stimulates GH release in normal subjects but suppresses GH release in acromegalic patients. Dopamine agonists bind to pituitary dopamine type 2 (D2) receptors and suppress GH secretion in some patients with acromegaly.² Oral dopamine agonists are only effective in less than 15% of patients.³ In selected patients with coexistent hyperprolactinaemia, however, dopamine agonists may sometimes be effective.⁴ Combined use of SRL and dopamine agonist therapy may improve therapeutic efficacy. Long-acting depot SRL preparations and longer-acting dopaminergic agents are preferred over the short-acting agents.⁵ Newer dopaminergic agents such as cabergoline appear to be promising.³

GH Receptor Antagonists

GH receptor antagonists are a relatively new class of pharmaceutical agents. Pegvisomant, the currently available agent, is a pegylated growth hormone analogue that both enhances affinity for the growth hormone receptor and prevents functional growth hormone–receptor signaling.³ Pegvisomant is used in patients with resistance to or intolerance of somatostatin analogues. The drug should be used in patients with resistant diabetes and those who do not have central compressive symptoms.³ The long-term effects of these drugs on tumour growth are still under investigation.⁴

Somatostatin Analogues

Somatostatin is a brain hormone that inhibits GH release. Octreotide is a synthetic form of somatostatin used in the treatment of acromegaly. Sandostatin^® LAR^®, a longer-acting slow-release form of octreotide, is available for the treatment of acromegaly.^3,6

Sandostatin LAR is administered intramuscularly once monthly (compared with 3 times a day for the standard formulation of octreotide). Efficacy of the slow-release form of octreotide in the control of GH, IGF-1, and clinical symptoms is similar to that of the Sandostatin^® Injection, and has been used as a safe and effective treatment for acromegaly for over 10 years.^3,6

The goals of therapy are to reduce GH and IGF-1 production, reduce tumour volume, and provide symptom relief—Sandostatin LAR provides proven efficacy in acromegaly.⁷

References: 1. Giustina A, Barkan A, Casanueva FF, et al. Criteria for cure of acromegaly: a consensus statement. J Clin Endocrinol Metab. 2000;85:526-529. 2. Melmed S, Jackson I, Kleinberg D, Klibanski A. Current treatment guidelines for acromegaly. J Clin Endocrinol Metab. 1998;83:2646-2652. 3. Melmed S. Medical progress: acromegaly. N Engl J Med. 2006;355:2558-2573. 4. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services. Acromegaly. Bethesda, MD: National Institutes of Health; 2008. NIH publication 08-3924. 5. Melmed S, Casanueva FF, Cavagnini F, et al; for the Acromegaly Treatment Consensus Workshop Participants. Guidelines for acromegaly management. J Clin Endocrinol Metab. 2002;87:4054-4058. 6. About Sandostatin Website. Novartis Core Labeling Text. Available at: http://www.sandostatin.com/about_sandostatin/novartis_core_summary/index.html. Accessed March 16, 2009. 7. Mercado M, Borges F, Bouterfa H, et al; on behalf of the SMS995B2401 Study Group. A prospective, multicentre study to investigate the efficacy, safety and tolerability of octreotide LAR (long-acting repeatable octreotide) in the primary therapy of patients with acromegaly. Clin Endocrinol. 2007;66:859-868.