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

Abstract

Context 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. Objectives 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. Design Multicenter retrospective study. Settings and patients Records were reviewed for 116 children (64 females, 52 males) with NF1 and OPGs followed at 4 Italian centers. Main outcome measures 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. Results 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). Conclusions 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.

Non-Oncological Neuroradiological Manifestations in NF1 and Their Clinical Implications

“…NF1 patients are known to be prone to CNS tumor development, and the natural history of optic pathway glioma as well as non-optic tumors has been largely described in the literature [ 8 , 9 , 10 , 11 ]. Besides tumor-related manifestations, NF1 is also characterized by a wide spectrum of CNS alterations, with variable impacts on functioning and life quality, which can be observed to varying degrees in up to 70% patients [ 12 , 13 ].…”

Retrospective Multicentric Study on Non-Optic CNS Tumors in Children and Adolescents with Neurofibromatosis Type 1

“…Twenty-eight patients were followed at the Neurofibromatosis Referral Center of the "Luigi Vanvitelli" University of Campania, Italy, and seven at Dana Children's Hospital, Tel Aviv Sourasky Medical Center, Israel. Some of the patients described in the present report were included in other previously published studies [6,[22][23][24]. Patient demographics and clinical data are summarized in Table 1.…”

“…The most common CNS tumor is optic pathway glioma (OPG), which is also a hallmark and diagnostic criteria of NF1 [5]. A low-grade glioma (LGG) is usually indolent and is only rarely life-threatening, but may also present more aggressive behavior and be responsible for significant morbidity [6,7]. In contrast, CNS tumors in adults with NF1 tend to be of higher histological grade and have a worse prognosis than those occurring in children [8][9][10].…”

Endocrine Conditions in Neurofibromatosis 1

“…The association of NF1 with endocrinopathies has been reported since 1920 [3]. The data on the incidence and prevalence of endocrine disorders in NF1 are scarce [4]. The most common endocrine disorders in NF1 are short stature with or without growth hormone deficiency (GHD), central precocious puberty, growth hormone excess (GHE).…”