Endocrine Abstracts

Introduction: McCune-Albright syndrome (MAS) is a rare disorder characterized by skeletal lesions, skin hyperpigmentation, and hyperfunctioning endocrinopathies. It is due to the postzygotic gain-of-function mutations in GNAS1, which encodes the α-subunit of the Gs signaling protein.

Case 1: A 13 year old boy presented initially with a femur fracture at the age of 5.5 years following minor injury. Café au lait patches were noted. Bone scan and skeletal survey revealed multiple FD involving the skull, long bones and pelvis. GNAS1 mutation analysis was negative. Peripheral precocious puberty was identified at the age of 6 years which subsequently trigged central puberty needing treatment with a combination of Bicalutamide, Anastrazole and GnRH analogues. He was noted to have asymmetrical testes with bilateral microlithiasis and the tumours markers were negative. He was tall with increased height velocity, high IGF1 and IGFBP3 and non-suppressed growth hormone to OGTT which was managed with monthly Lanreotide injections. He was also diagnosed with hypophosphatemic rickets with elevated FGF23 (140RU/ml), which was managed with phosphate supplements and 1α Calcidol. Prolactin levels have been persistently high but he is asymptomatic. He is currently 13 years old and has completed the treatment for early puberty and growth hormone excess. Management of hypophosphatemic rickets continues to be a challenge and Burosumab treatment is being considered.

Case 2: A 1.5year old baby girl presented with episodic vaginal bleeding since the age of 3 months, associated with breast development. Café au lait patches were noted and GNAS1 mutation was identified. Estradiol was high with suppressed LH and FSH. Cystic lesions with multiple daughter cysts and a 4.7 cm pear shaped uterus with endometrial thickness of 2.2mm were noted in the ultrasound. She was started on Letrozole with good clinical effect and subsequent imaging revealed regression of ovarian cysts with reduction of uterine and ovarian size.

Conclusion: MAS could present with a wide range of phenotypic features and could pose challenges in management especially when there is multisystem involvement. A close surveillance for evolving skeletal and extra skeletal complications is necessary.