Pegvisomant for the Treatment of gsp-mediated Growth Hormone Excess in Patients with McCune-Albright Syndrome. [J Clin Endocrinol Metab] Journal article

Context: Growth hormone (GH) excess affects approximately 20% of the patients with McCune-Albright Syndrome (MAS). MAS is caused by sporadic, post zygotic, activating mutations in the GNAS gene, which codes for the cAMP-regulating protein, Gsalpha (gsp oncogene). These same mutations are found in approximately 1/3 of the sporadic cases of acromegaly.
Objective: 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. Setting and
Patients: Five MAS patients with GH excess were treated with 20 mg/day sc injection of pegvisomant for 12 weeks in a randomized, double blind placebo-controlled crossover study at the National Institutes of Health. Main Outcome Measures: The primary measure of efficacy was normalization of insulin growth factor I (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.
Results: Combined mean changes in serum IGF-I at 6 and 12 weeks were -236.4 ng/ml (53%, P < 0.005) and -329.8 ng/ml (62%, P < 0.001), respectively. IGF1BP-3 decreased by 0.8 mg/L (24%, P < 0.01) and 2.9 mg/L (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 the two regimens were similarly effective.
Conclusions: Pegvisomant effectively reduced IGF-I and IGFBP-3 levels in gsp-mediated GH excess but had no effect on FD.

J Clin Endocrinol Metab