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

• Published in: Clinical endocrinology (Oxford) Vol. 89; no. 1; pp. 56 - 64
• Main Authors: Tessaris, Daniele, Boyce, Alison M, Zacharin, Margaret, Matarazzo, Patrizia, Lala, Roberto, De Sanctis, Luisa, Collins, Michael T
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.07.2018
• Subjects: Bone dysplasia; bone fibrous dysplasia; Bone marrow; Endocrine disorders; Fibrous dysplasia; GH hypersecretion; Growth factors; Growth hormones; GSalfa; Hyperactivity; Hyperpigmentation; Insulin; Insulin-like growth factor I; McCune‐Albright; Octreotide; Optic neuropathy; Pain; Patients; Pituitary; Tumors; GH hypersecretion; pituitary; octreotide; GSalfa; bone fibrous dysplasia; McCune-Albright
• ISSN: 0300-0664; 1365-2265; 1365-2265
• DOI: 10.1111/cen.13722

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 (IGF1) 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 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 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‐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.