Skeletal and endocrine manifestations of McCune-Albright syndrome in patients with fibrous dysplasia

Abstract

McCune-Albright syndrome (MAS) is defined by a triad of fibrous dysplasia (FD), hyperfunctioning endocrinopathies, and café-au-lait spots. FD, characterized by the fibrous replacement of healthy bone, is a major source of morbidity in MAS. To characterize skeletal involvement and associated endocrinopathies in patients with MAS/FD, we conducted a retrospective review of patients with the diagnosis of both MAS and FD treated at our center between 1989 and 2024. Forty-three patients (29 female; median diagnosis age: 13.1 years) were included, with 41 presenting with polyostotic FD. Among these, 19 had both craniofacial and extracraniofacial involvement, 4 had craniofacial-only, and 18 had extracraniofacial-only disease. The lower extremities were most commonly affected (n=32), followed by the skull (n=25). All patients with lower extremity FD had femoral involvement; 10 had bilateral disease. Chronic pain was reported by 23 patients. Among those with lower extremity FD, 16 had deformities—most commonly leg length discrepancies (n=10) and shepherd’s crook deformities (n=6). Femoral fractures occurred in 21 patients, with higher risk in those with deformities (p=0.006). Precocious puberty occurred at a median age of 4.8 years. Hyperfunctioning endocrinopathies were observed in 17 patients: cortisol excess (n=2), hyperthyroidism (n=8), elevated GH/IGF-1 (n=10), and phosphate wasting (n=6). Hormone levels, age at puberty, and age at diagnosis were not associated with fracture or deformity risk (p>0.05). One patient developed osteosarcoma requiring above-knee amputation. In conclusion, extracraniofacial skeletal disease and endocrinopathies are common in MAS. Coordinated interdisciplinary care is vital to manage deformities and systemic complications.