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Optimizing Control of Acromegaly: Integrating a Growth Hormone Receptor Antagonist into the Treatment Algorithm

University of North Carolina at Chapel Hill (D.R.C.), Chapel Hill, North Carolina 27599; Division of Endocrinology/Metabolism, Neurology, and Hematology/Oncology (K.C.), Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Hyogo 650-0017, Japan; Department of Medicine (P.U.F.), Columbia University College of Physicians and Surgeons, New York, New York 10032; Pituitary Research Unit (K.K.Y.H.), Garvan Institute of Medical Research, and Department of Endocrinology, St. Vincent’s Hospital, Darlinghurst 2010, Australia; Neuroendocrine Unit (A.K.), Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114; Cedars Sinai Medical Center (S.M.), University of California School of Medicine, Los Angeles, California 90048; Department of Endocrinology (S.M.S., P.J.T.), Christie Hospital, Manchester M20-4BX, United Kingdom; Division of Endocrinology (C.J.S.), Department of Medicine, Charite Campus Mitte, D-80336 Berlin, Germany; and Department of Medicine (M.O.T.), University of Virginia Health System, Charlottesville, Virginia 22908

Address correspondence and reprint requests to: David Clemmons, M.D., Professor of Medicine, University of North Carolina at Chapel Hill, 6111 Thurston-Bowles Building, CB #7170, Chapel Hill, North Carolina 27599. E-mail: endo{at}med.unc.edu.

Acromegaly is associated with significant morbidities and a 2- to 3-fold increase in mortality because of the excessive metabolic action of GH and IGF-I, a marker of GH output. Reductions in morbidity correspond with decreases in IGF-I, and mortality is lowered following normalization of IGF-I or GH levels. Therefore, this has become an important end point. Current guidelines for the treatment of acromegaly have not considered recent advances in medical therapy, in particular, the place of pegvisomant, a GH receptor antagonist. Treatment goals include normalizing biochemical markers, controlling tumor mass, preserving pituitary function, and relieving signs and symptoms. Surgery reduces tumor volume and is considered first-line therapy. Radiation reduces tumor volume and GH and IGF-I levels, but the onset of action is slow and hypopituitarism typically develops. Therefore, pharmacotherapy is often used following surgery or as first-line therapy for nonresectable tumors. Dopamine agonists can be considered in patients exhibiting minimal disease or those with GH-prolactin-cosecreting tumors but will not achieve hormone normalization in most patients. Somatostatin analogs effectively suppress GH and IGF-I in most patients, but intolerance (e.g. diarrhea, cramping, gallstones) can occur. Pegvisomant, the newest therapeutic option, blocks GH action at peripheral receptors, normalizes IGF-I levels, reduces signs and symptoms, and corrects metabolic defects. Pegvisomant does not appear to affect tumor size and has few adverse effects. Pegvisomant is the most effective drug treatment for acromegaly in normalizing IGF-I and producing a clinical response; it is the preferred agent in patients resistant to or intolerant of somatostatin analogs.

This meeting was supported by an unrestricted educational grant from Pharmacia Corporation.

Abbreviations: GHRA, GH receptor antagonist; GTT, glucose tolerance test; LFT, liver function test; PRL, prolactin; SRL, somatostatin receptor ligand.

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