Growth hormone—Insulin‐like growth factor 1 axis hyperactivity on bone fibrous dysplasia in McCune‐Albright Syndrome. (17th May 2018)

• Record Type: Journal Article
• Authors: Tessaris, Daniele; Boyce, Alison M; Zacharin, Margaret; Matarazzo, Patrizia; Lala, Roberto; De Sanctis, Luisa; Collins, Michael T
• Is Part Of: Clinical endocrinology. Volume 89:Number 1(2018)
• Page Start: 56
• Page End: 64
• Publication Date: 2018-05-17
• Subjects: bone fibrous dysplasia -- GH hypersecretion -- GSalfa -- McCune‐Albright -- octreotide -- pituitary; Endocrinology -- Periodicals; 616.4005
• DOI: 10.1111/cen.13722
• Languages: English
• ISSNs: 0300-0664

Abstract

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.