Endocrine Abstracts

Background: McCune Albright syndrome (MAS) is a rare mosaic genetic disorder affecting 1/100 000 to 1/1 000 000 of the population. It arises from a somatic gain-of-function mutation in GNAS gene. The clinical picture is complex and includes fibrous dysplasia (FD), café-au-lait spots, precocious puberty and other hyperactive endocrinopathies. The degree of FGF23 overproduction is correlated with FD severity, and frank hypophosphatemia occurs only in patients with extensive skeletal involvement, resulting in frequent fractures, pain, increased propensity for deformities, and muscle weakness. Burosumab is a monoclonal antibody that targets FGF23, indicated for the treatment of hypophosphatemic rickets and tumor-induced osteomalacia caused by overproduction of FGF23. To date, there is no evidence on the effectiveness and safety of burosumab treatment in adults with FD/MAS.

Case presentation: A 27-year-old male with MAS was under the care of the Endocrinology Department for persistent hypophosphatemia despite treatment with oral phosphate supplements and alfacalcidol. MAS was diagnosed at the age of 6 years and his medical history included precocious puberty, multiple fractures, skeletal deformities, muscle weakness and exacerbated skeletal pain due to severe FD. The patient was diagnosed with GH excess at the age of 22 years and has been treated with pasireotide 40 mg every 4 weeks i.m. with normalization of IGF-1 level for age and sex. Because of persistent hypophosphatemia (serum phosphate 0.38 mmol/l) resulting from FGF23 excess (serum FGF23 495kRU/L normal <100), bone pain and frequent fractures, the treatment with burosumab has been attempted (1 mg/kg body weight s.c. every 4 weeks). Over the 10-month course of treatment, the patient reported improved general well-being, reduced bone pain and increased muscle strength. Normalization of serum phosphate 0.87 mmol/l, PTH 51.6 pg/ml and significant reduction in alkaline phosphatase levels from 1022.2 U/l to 592.6 U/l were achieved. No adverse effects of the short-term therapy were observed.

Conclusions: This is the first reported case of burosumab treatment in an adult patient with FGF23-related hypophosphatemia in MAS. In our case, positive effects of the therapy were observed, both in terms of the patient’s reported well-being and in terms of calcium-phosphate balance and bone markers. However, a longer follow-up in a larger group of adult patients with MAS seems necessary.