Growth Hormone excess in patients with McCune-Albright Syndrome: a literature systematic review and pooled data analysis

Abstract Growth hormone (GH) excess in Fibrous dysplasia/McCune-Albright (FD/MAS) syndrome has detrimental effects on Craniofacial fibrous dysplasia (CFD), leading to visual and hearing impairment, therefore early diagnosis and treatment is paramount. Current data on early clinical manifestations and management is scarce. A systematic search retrieved studies reporting diagnosis and management of GH excess in FD/MAS. 184 patients from 101 publications were included. Clinical presentation ranged from asymptomatic to clinically overt GH excess. Craniofacial fibrous dysplasia was present in 174 patients (98.9%), with progressive facial asymmetry being the most reported clinical sign. Median age at FD/MAS diagnosis was 12 years (IQR 6–25), whereas in most patients GH excess was diagnosed in the third decade (median 22 years; IQR 11–33). GH was unsuppressed on suppression testing in 64 (83.1%), while 13 (16.9%) had a paradoxical increase. Four patients had unsuppressed GH despite normal IGF1 levels. Pituitary imaging revealed a normal gland in 20.5%, diffuse pituitary hyperplasia in 9.6%, and a pituitary adenoma in 69.9%. Hyperprolactinemia was the most common associated endocrinopathy (72.1%). Medical therapy was the most frequent first-line treatment. Surgery was limited by craniofacial fibrous dysplasia, and radiotherapy poses a risk of malignant transformation in FD. Clinicians should maintain a high index of suspicion for GH excess, particularly, though not exclusively, in patients with craniofacial fibrous dysplasia progression. Systematic reporting in dedicated registries, rather than in isolated case reports, is essential to improve understanding and management.