Endocrine Abstracts

McCune-Albright Syndrome (MAS) is a rare congenital sporadic disorder due to an embryonic post-zygotic somatic mutation in the GNAS1 gene, defined by the triad of peripheral precocious puberty (PPP), unilateral café-au-lait spots and fibrous dysplasia (FD) of bone. PPP or precocious pseudopuberty is the most common endocrinopathy seen in MAS. Other hyperfunctioning endocrinopathies include hyperthyroidism, acromegaly, FGF23-mediated hypophosphatemia and neonatal hypercortisolism. A 2.6-year old girl with history of a recent 15 mm left ovarian cyst was admitted for repeated vaginal bleeding and slightly elevated growth rate. Physical examination: bilateral thelarche Tanner stage 3, menarche, advanced stature + 0.94 S.D. towards the mean, lumbosacral, café-au-lait spots without axillary-pubic hair or bone deformities. MAS was assessed. Hormonal evaluation: basaline estradiol (E2) values fluctuated between 10.7–71.5 pg/ml, with reduced serum gonadotrophin (LH ≤ 0.13 mUI/ml, FSH ≤ 0.21 mUI/ml), normal TSH, FT4, PRL, IGF1, basal cortisol, testosterone, DHEAS, 25-OH vitamin D, slightly elevated 17-OH progesterone (2.6 ng/ml), low PTH (14 pg/ml) associated with normal serum phosphorus and calcium, high alkaline phosphatase (599U/l) and osteocalcin (66.7 ng/ml). The first Diphereline stimulation test (DST) 0.1 mg SC showed LH = 0.68 mUIm/l at 4 h. The 6 month DST was positive with an increasing tendency of gonadotrophin suggesting central puberty (LH and FSH at 4 h were 4.5 mU/ml respectively 7.19 mU/ml) and E2 = 68.8 pg/ml at 24 h. Abdominal ultrasound: enlarged uterus of 7.5 cc, 41 mm, thickened endometrium, no ovarian cysts, normal adrenal glands. Breast ultrasound: 13.6/15.8 mm right and 16.7/15.5 mm left breast buds. Bone age: 4 years old. Cranial CT scan and pelvic, bilateral femur and knee X-rays: polyostotic fibrous dysplasia of the neuro- and viscerocranium, bilateral iliac and femoral neck and left proximal tibial osteosclerosis areas. Pituitary MRI and thyroid ultrasound were normal. The prescribed treatment consisted of Letrozole 1.5 mg/m²/day associated with Diphereline 1.87 mg/28 days and 1-alphacalcidol 0.25 µg/day. One month later, follow-up revealed: disappearance of vaginal bleedings and normal E2. PPP in girls results from autonomous ovarian tissue activation with recurrent estrogen-secreting ovarian cysts. Due to prolonged exposure to high E2 levels with maturation of the hypothalamic-pituitary axis, PPP may progress to central precocious puberty (CPP). Treatment includes aromatase inhibitors alone or in combination with gonadotropin-releasing hormone agonists. FD is associated with increased osteoclastic activity and elevation of biochemical markers of bone turnover. Bisphosphonates have been alleged to improve FD symptoms in MAS. As the age of onset and the severity of the MAS clinical manifestations are variable, close long-term follow-up and periodical screening are required. Therefore MAS management is challenging and involves a multidisciplinary team.