In fibrous dysplasia (BFD), normal bone and bone marrow are replaced by fibro-osseous tissue, leading to fracture, deformity and pain. BFD may be isolated, or in association with cutaneous hyperpigmentation and/or hyperfunctioning endocrinopathies, termed McCune-Albright syndrome (MAS). GH hypersecretion has been described in 10%-20% of MAS-BFD patients. Aim of the study was to determine the impact of GH-insulin like growth factor 1 (IGF1) axis hyperactivity on MAS-BFD morbidities and the efficacy of GH excess therapy. A multicentric cross-sectional analysis was conducted on three different MAS cohorts. From 195 MAS patients, 37 subjects (19%) with GH excess were identified and compared with 34 MAS controls without GH hypersecretion. Mean head circumference SDS was significantly higher in GH excess: 4.025 SDS vs 0.683 SDS (P<.0001). The risk of optic neuropathy (Odds ratio 4.231; P=.039), hearing deficit (Odds ratio 2.961; P=.0481), facial asymmetry (Odds ratio 6.563; P=.0192), malignancies (Odds ratio 15.24; P=.0173) were higher in GH excess group. Overall, pharmacotherapy (octreotide alone 10-30mg/mo or with pegvisomant 10-20mg/d) was effective in IGF1 normalization (IGF1 Z-score between -2 and +2 SDS) in 21/29 patients (72.4%) with good compliance to the regimen. Late diagnosis and GH excess treatment after 16years old of age was associated with an increased risk of optic neuropathy (Odds ratio 4.500; P=.0491) and growth of pituitary adenomas (Odds ratio 7.846; P=.050). GH-IGF1 hyperactivity increases risk of morbidities in MAS. Medical therapy is effective in normalizing IGF1 in most patients, and early treatment during paediatric age is associated with a decreased risk of optic neuropathy and GH-secreting adenomas growth.