ESPE Abstracts (2016) 86 FC3.5

Septo-optic Dysplasia Spectrum: Pubertal Features of a Large Cohort of Children and Adolescents with Septo-optic Dysplasia, Congenital Hypopituitarism and Optic Nerve Hypoplasia from a Single Centre

Manuela Cerbone, Maria Guemes, Nicola Improda & Mehul T Dattani


London Centre for Pediatric Endocrinology and Diabetes, University College London and Great Ormond Street Hospitals, London, UK


Background: Children with septo-optic dysplasia (SOD) and related disorders can present with either hypogonadotropic hypogonadism or precocious puberty. This phenotypic variability remains unexplained.

Objective and hypotheses: To compare pubertal characteristics of SOD with isolated congenital hypopituitarism (CPHD) and optic nerve hypoplasia (ONH).

Method: Retrospective longitudinal data collection from 259 patients with: SOD (n=171), CPHD (n=53) or ONH (n=35).

Results: In males, under-virilized external genitalia were observed at birth in 70% CPHD, 43% SOD, and 14% ONH (P=0.005). Of males with under-virilized external genitalia, 39% SOD and 100% CPHD were diagnosed with probable GnRH deficiency (P=0.002). Compared with SOD, CPHD had lower testosterone responses to 3 days (P=0.015) and 3 weeks (P=0.056) of HCG, and lower LH (P<0.0001) and FSH (P<0.0001) concentrations on GnRH testing. Spontaneous onset of puberty was observed in 93% ONH (n=14), 82% SOD (n=66) and 45% CPHD (n=15) (P<0.001) and occurred at similar ages in the three groups. A likely diagnosis of GnRH deficiency was made in 28% (n=72) SOD and 75% (n=24) CPHD (P=0.0001). Sex steroid treatment was required in 8% SOD (n=95) and 32% CPHD (n=28) (P<0.002) to start (7 SOD and 7 CPHD) or progress (1 SOD, 2 CPHD) through puberty. 12% of SOD (n=98) and 12% of ONH (n=25) needed treatment for cessation of early/precocious puberty. Premature thelarche occurred in 2 ONH and 5 SOD, premature menarche in 2 SOD and premature adrenarche in 4 SOD and 3 ONH.

Conclusion: Our data demonstrate, particularly in males, a more frequent and severe impairment of GnRH function in CPHD as compared to SOD/ONH in whom GnRH function is often retained with early/precocious puberty and adrenarche. These data suggest that distinct genetic and/or environmental insults at different stages of brain development may dictate the variability of phenotype observed.

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