Pretreatment Endocrine Disorders Due to Optic Pathway Gliomas in Pediatric Neurofibromatosis Type 1: Multicenter Study

• Published in: The journal of clinical endocrinology and metabolism 2020-06, Vol.105 (6), p.e2214-e2221
• Main Authors: Santoro, Claudia, Perrotta, Silverio, Picariello, Stefania, Scilipoti, Martina, Cirillo, Mario, Quaglietta, Lucia, Cinalli, Giuseppe, Cioffi, Daniela, Di Iorgi, Natascia, Maghnie, Mohamad, Gallizia, Annalisa, Parpagnoli, Maria, Messa, Federica, De Sanctis, Luisa, Vannelli, Silvia, Marzuillo, Pierluigi, Miraglia Del Giudice, Emanuele, Grandone, Anna
• Format: Article
• Language: English
• Subjects: Adolescent; Chemotherapy; Child; Child, Preschool; Children; Endocrine disorders; Endocrine System Diseases - epidemiology; Endocrine System Diseases - etiology; Endocrine System Diseases - pathology; Female; Follow-Up Studies; Genetic disorders; Glioma; Growth hormones; Humans; Hypothalamus; Infant; Infant, Newborn; Italy - epidemiology; Male; Neurofibromatosis; Neurofibromatosis 1 - physiopathology; Neuroimaging; Neurological disorders; Optic Nerve Glioma - complications; Patients; Physical growth; Prevalence; Prognosis; Puberty; Recklinghausen's disease; Retrospective Studies; Surgery; Survival Rate; Tumors
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgaa138

Up to 20% of children with neurofibromatosis type 1 (NF1) develop low-grade optic pathway gliomas (OPGs) that can result in endocrine dysfunction. Data on prevalence and type of endocrine disorders in NF1-related OPGs are scarce. The aim of the study was to determine the prevalence of endocrine dysfunctions in patients with NF1 and OPGs and to investigate predictive factors before oncological treatment. Multicenter retrospective study. Records were reviewed for 116 children (64 females, 52 males) with NF1 and OPGs followed at 4 Italian centers. We evaluated endocrine function and reviewed brain imaging at the time of OPG diagnosis before radio- and chemotherapy and/or surgery. OPGs were classified according to the modified Dodge classification. Thirty-two children (27.6%) with a median age of 7.8 years had endocrine dysfunctions including 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 a multivariate cox regression analysis, hypothalamic involvement was the only independent predictor of endocrine dysfunctions (hazard ratio 5.02 [1.802-13.983]; P = .002). Endocrine disorders were found in approximately one-third of patients with Neurofibromatosis type 1 and OPGs before any oncological treatment, central precocious puberty being the most prevalent. Sign of diencephalic syndrome and growth hormone hypersecretion, although rare, could be predictive of optic pathway gliomas in NF1. Tumor location was the most important predictor of endocrine disorders, particularly hypothalamic involvement.