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- Title
Pegvisomant for the treatment of gsp-mediated growth hormone excess in patients with McCune-Albright syndrome.
- Authors
Akintoye, Sunday O.; Kelly, Marilyn H.; Brillante, Beth; Cherman, Natasha; Turner, Sarah; Butman, John A.; Robey, Pamela G.; Collins, Michael T.
- Abstract
<bold>Context: </bold>GH excess affects approximately 20% of the patients with McCune-Albright syndrome (MAS). MAS is caused by sporadic, postzygotic, activating mutations in the GNAS gene, which codes for the cAMP-regulating protein, G(s)alpha (gsp oncogene). These same mutations are found in approximately one third of the sporadic cases of acromegaly.<bold>Objective: </bold>We examined efficacy of the GH receptor antagonist, pegvisomant, in controlling gsp oncogene-mediated GH excess and skeletal disease (fibrous dysplasia of bone) associated with MAS.<bold>Setting and Patients: </bold>Five MAS patients with GH excess were treated with 20 mg/d sc injection of pegvisomant for 12 wk in a randomized, double-blind, placebo-controlled crossover study at the National Institutes of Health.<bold>Main Outcome Measures: </bold>The primary measure of efficacy was normalization of IGF-I. Secondary outcome measures were reduction in serum IGF binding protein-3 (IGFBP-3), improvement of fatigue and sweating, and reduction in markers of bone metabolism and bone pain.<bold>Results: </bold>Combined mean changes in serum IGF-I at 6 and 12 wk were -236.4 ng/ml (53%, P < 0.005) and -329.8 ng/ml (62%, P < 0.001), respectively. IGFBP-3 decreased by 0.8 mg/liter (24%, P < 0.01) and 2.9 mg/liter (37%, P < 0.005), respectively. There were no significant changes in signs and symptoms of acromegaly or markers of bone metabolism and bone pain, nor was there a significant change in pituitary size. Retrospective comparison of the degree of control achieved with pegvisomant vs. other medications (long-acting octreotide +/- dopamine agonist) in the same group showed that the two regimens were similarly effective.<bold>Conclusions: </bold>Pegvisomant effectively reduced IGF-I and IGFBP-3 levels in gsp-mediated GH excess but had no effect on fibrous dysplasia.
- Subjects
BONE metabolism; CARRIER proteins; CELL receptors; COMPARATIVE studies; CROSSOVER trials; FATIGUE (Physiology); FIBROUS dysplasia of bone; MAGNETIC resonance imaging; RESEARCH methodology; MEDICAL cooperation; MEMBRANE proteins; GENETIC mutation; PAIN; PERSPIRATION; PITUITARY gland; PLACEBOS; RESEARCH; RESEARCH funding; SOMATOMEDIN; CHROMOGRANINS; EVALUATION research; HUMAN growth hormone; RANDOMIZED controlled trials; TREATMENT effectiveness; BLIND experiment; THERAPEUTICS
- Publication
Journal of Clinical Endocrinology & Metabolism, 2006, Vol 91, Issue 8, p2960
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2005-2661