ESPE Abstracts (2015) 84 P-2-521

A Novel Entity Characterised by GH Deficiency and Central Precocious Puberty in Two Siblings and their Father, in the Absence of Central Nervous System Defect

Antonis Voutetakisa, Dimitris Chiotisa, Maria Dracopoulou-Vaboulia, Alexandra-Maria Magiakoua, Georgia Chrousosb, George Chrousosa & Catherine Dacou-Voutetakisa

aDepartment of Pediatrics, Division of Endocrinology, Metabolism and Diabetes, Medical School, National and Kapodistrian University of Athens, Athens, Greece; bPediatric Ophthalmology Department, MITERA Childrens’ Hospital, Athens, Greece

Background: The association of GH deficiency (GHD) with central precocious puberty (CPP) has been reported in individuals with central nervous system (CNS) abnormalities, congenital or acquired. Co-existence of GHD and CPP has been rarely reported, always as an isolated, sporadic disorder.

Objective and hypotheses: To present the familial occurrence of combined GHD and CPP.

Method: GH was measured post L DOPA, glucagon and GHRH and gonadotropins were determined post GnRH administration, using established methodology. CNS was evaluated using brain magnetic resonance imaging (MRI).

Results: Two siblings were examined for short stature; a female at age 11 years and her brother at age 8.2 years. The girl, reportedly, had puberty initiation at 6 years and menarche at 7.8 years. Peak GH on two provocative tests was <1 ng/ml with no response to GHRH, while results of GnRH test disclosed CPP. The girl’s pathology wasn’t recognized promptly and received no therapy, reaching a final height of 122 cm (−8 SDS). The boy’s height at age 8.2 years was 107 cm (−4.6 SDS). He entered puberty at age 10 years. He received rhGH and GnRHan and reached a final height of 170 cm (−1.1 SDS), the target height being 161.5±4.5 cm. On provocative testing, the mother had normal GH peak (26 ng/ml), while the father (Ht SDS −3) had low GH (2 ng/ml). There was no evidence of optic nerve atrophy or CNS defect.

Conclusion: The combined familial defect of GHD and CPP most likely represents a novel entity, possibly inherited as an autosomal dominant trait. It should be attributed to a mutated transcription factor affecting both GHRHR and GnRHR or the somatotrophs and gonadotrophs acting in a diverse manner; loss and gain of function respectively. The existence of such complex natural prototypes can act as the key to understand pituitary development and function.