Growth hormone—Insulin‐like growth factor 1 axis hyperactivity on bone fibrous dysplasia in McCune‐Albright Syndrome

Summary Context 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 ( IGF 1) axis hyperactivity on MAS ‐ BFD morbidities and the efficacy of GH excess therapy. Design and patients 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. Results 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 10‐30 mg/mo or with pegvisomant 10‐20 mg/d) was effective in IGF 1 normalization ( IGF 1 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 16 years 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). Conclusions GH ‐ IGF 1 hyperactivity increases risk of morbidities in MAS . Medical therapy is effective in normalizing IGF 1 in most patients, and early treatment during paediatric age is associated with a decreased risk of optic neuropathy and GH ‐secreting adenomas growth.