MON-247 Clinical Characterization of Female Peripheral Precocious Puberty Due to McCune-Albright Syndrome

Abstract

Background: McCune-Albright syndrome (MAS) is a rare and sporadic disease caused by a post-zygotic mutation in GNAS1 gene. It is characterized by the classical triad of polyostotic fibrous dysplasia, café-au-lait skin spots and peripheral precocious puberty (PPP). However, clinical presentation of MAS is highly variable depending on mosaic tissue distribution of mutant-bearing cells. Due to the low prevalence of MAS, detailed data of clinical and laboratory presentation are scarce. Aim: To describe the clinical and hormonal features of PPP due to MAS from a single tertiary center. Patients and Methods: The medical records of girls with PPP due to MAS diagnosed and treated from 1990 and 2018 were systematically revised. We analyzed initial clinical presentation, Tanner stage, gonadotropins and estradiol levels, and pelvic ultrasound findings of a MAS cohort. Results: From a total of 37 patients (35 girls and 2 boys) with clinical diagnosis of MAS, 14 (37.8%) female patients presented PPP. The first clinical manifestation was thelarche in 12/14 (85.7%), followed by vaginal bleeding in 7/14 (50%), and pubarche in 5/14 (35.7%). The mean height (SDS) was 109 ± 35 cm (SDS: 1.3 ± 1.6). All girls had Tanner-staging ≥ B2 (ranging from B2-B4) and 8/14 (57.1%) had pubarche. Fibrous bone dysplasia was detected in 9/14 (64.2%) by bone scintigraphy and café-au-lait skin spots were found in 10/14 (71.4%) of these girls. Menarche occurred at mean age of 3.75 ± 2 yr (2 - 7.2 yr). Mean basal LH and FSH were 0.36 ± 0.24 IU/L and 1.27± 1.0 IU/L, respectively. Estradiol levels ranged from < 13 to 783 pg/mL (mean 96.8 pg/mL). Basal estradiol levels were at prepubertal range in 8/14 (57%) on several occasions. All girls underwent a GnRH-analogue stimulated test showing a prepubertal LH response (2.9 ± 2.1 IU/L); 2 patients showed completely suppressed basal and stimulated gonadotropin levels. Uni- or bilateral ovarian cysts were identified in 9/14 patients (64.2%) being bilateral in 50% of them. Mean ovarian volumes were 2.63 ± 1.4 cm³ for right and 2.05 ± 1.9 cm³ for left ovarian, with mean cyst volumes ranging from 2.7 to 45 cm3. Other endocrine hyperfunctions were not identified in this MAS cohort. Conclusion: PPP in girls with MAS has a heterogeneous clinical presentation. It was characterized by menarche at very early age as a first sign associated with variable values of estradiol levels (pre- and pubertal) and ovarian sizes. Pediatric endocrinologists must be aware of atypical clinical and laboratory presentation of PPP due to MAS.