Pretreatment endocrine disorders due to optic pathway gliomas in pediatric neurofibromatosis type 1: Multicenter study

Context: Up to 20% of children with neurofibromatosis type 1 (NF1) develop low-grade opticpathway gliomas (OPGs) that can result in endocrine dysfunction. Data on prevalence and typeof endocrine disorders in NF1-related OPGs are scarce.Objectives: The aim of the study was to determine the prevalence of endocrine dysfunctions inpatients with NF1 and OPGs and to investigate predictive factors before oncological treatment.Design: Multicenter retrospective study.Settings and patients: Records were reviewed for 116 children (64 females, 52 males) with NF1and OPGs followed at 4 Italian centers.Main outcome measures: We evaluated endocrine function and reviewed brain imaging at thetime of OPG diagnosis before radio-and chemotherapy and/or surgery. OPGs were classifiedaccording to the modified Dodge classification.Results: Thirty-two children (27.6%) with a median age of 7.8 years had endocrine dysfunctionsincluding central precocious puberty in 23 (71.9%), growth hormone deficiency in 3 (9.4%),diencephalic syndrome in 4 (12.5%), and growth hormone hypersecretion in 2 (6.2%). In amultivariate cox regression analysis, hypothalamic involvement was the only independentpredictor of endocrine dysfunctions (hazard ratio 5.02 [1.802-13.983]; P =.002).Conclusions: Endocrine disorders were found in approximately one-third of patients withNeurofibromatosis type 1 and OPGs before any oncological treatment, central precocious puberty being the most prevalent. Sign of diencephalic syndrome and growth hormonehypersecretion, although rare, could be predictive of optic pathway gliomas in NF1. Tumorlocation was the most important predictor of endocrine disorders, particularly hypothalamicinvolvement.