Growth hormone-Insulin-like growth factor 1 axis hyperactivity on bone fibrous dysplasia in McCune-Albright Syndrome.
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.
['Tessaris|Daniele|D|0000-0002-6484-4371', 'Boyce|Alison M|AM|', 'Zacharin|Margaret|M|', 'Matarazzo|Patrizia|P|', 'Lala|Roberto|R|', 'De Sanctis|Luisa|L|', 'Collins|Michael T|MT|']
D000293:Adolescent D000328:Adult D002648:Child D002675:Child, Preschool D003430:Cross-Sectional Studies D005260:Female D005359:Fibrous Dysplasia, Polyostotic D013006:Growth Hormone D006801:Humans D007223:Infant D007334:Insulin-Like Growth Factor I D008297:Male D015337:Multicenter Studies as Topic D055815:Young Adult
bone fibrous dysplasia McCune-Albright GH hypersecretion octreotide pituitary GSalfa