ESPE Abstracts

Background: The clinical manifestations of McCune-Albright syndrome (MAS) are diverse, typically including fibrous dysplasia (FD), café au lait spots, and endocrine hyperfunction, most commonly gonadotropin-independent precocious puberty (GIPP). Management of endocrinopathies in MAS varies by the affected organs. Treatment options for GIPP include clinical observation, aromatase inhibitors (AIs), ketoconazole, medroxyprogesterone acetate, selective estrogen receptor modulators, or pure estrogen receptor blockers. For Cushing syndrome (CS), ketoconazole and metyrapone can be utilized. Patients with FD can be treated with medical treatments with intravenous bisphosphonates, denosumab, or burosumab, as well as surgical interventions to correct and prevent deformities and decompress nerves.

Objective: To describe the clinical characteristics and management outcomes of patients with MAS.

Methods: Clinical data of six MAS patients from a tertiary center in Thailand were obtained.

Results: The most common initial presentation was thelarche with vaginal bleeding, observed in three of six cases, followed by bone pain/deformity resulting from FD, seen in two of six cases. Interestingly, one patient manifested solely neonatal CS without other features of MAS and subsequently developed GIPP at 1.1 years of age. In this instance, diagnostic confirmation was facilitated through genetic testing. Another patient who initially presented with craniofacial FD also developed GIPP. Overall, GIPP manifested in five of six patients, with the age of onset ranging from 1.1 to 6.6 years. Among these, two progressed to secondary central precocious puberty (CPP). One patient with FD alongside café au lait spots was diagnosed with CPP, without a history of GIPP. FD developed totally in four of six patients, with only one exhibiting concurrent hypophosphatemic rickets. No other endocrinopathies were identified in this cohort. In terms of treatment, four girls with GIPP were successfully treated with letrozole, a second-generation AI, confirmed by a regression of breast tissue and ovarian cysts, menstrual cessation, and decreased estradiol levels. Neither ovarian cyst torsion nor signs of androgen excess were noted. The patient with CS and subsequent GIPP was treated with ketoconazole to simultaneously suppress cortisol and estrogen production. Patients experiencing CPP were treated with GnRH agonists. Patients with FD were treated with intravenous bisphosphonates, and some required surgical intervention.

Conclusion: MAS naturally manifests a broad spectrum of phenotypes over time, and timely intervention for endocrinopathies and FD optimizes clinical outcomes. In this series, GIPP was successfully treated with AIs. Ketoconazole may be considered if CS coexists with GIPP. GnRH agonists can be administered in cases of CPP.