title: Neuroendocrine Morbidity After Pediatric Optic Gliomas: A Longitudinal Analysis of 166 Children Over 30 Years.
abstract: BACKGROUND
  Fifty percent of pediatric low-grade gliomas affect the optic pathway, hypothalamus, and suprasellar areas (OP/HSGs), resulting in significant long-term neuroendocrinopathy.
  
  
  OBJECTIVE
  This study aimed to dissect tumor- from treatment-related risk factors for OP/HSG-associated neuroendocrinopathy.
  
  
  METHODS
  This was a retrospective case notes analysis of 166 children with newly diagnosed OP/HSGs at our quaternary center between 1980 and 2010 by multivariate Cox, linear, and logistic regression.
  
  
  RESULTS
  Patients were of median (range) age 4.9 (0.2-15.4) years at diagnosis and followed up for 8.3 (0.04-26.8) years. Despite high 20-year overall survival (81.0%), progression-free and endocrine event-free survival (EEFS) were 47.2 and 20.8%, respectively. EEFS declined up to 15 years post-diagnosis, with hypothalamic involvement (P < .001) being implicated more than radiotherapy (P = .008) in earlier endocrinopathy; the reverse being true of its density (radiotherapy P < .001; hypothalamic involvement P = .006). GH deficiency (GHD) was most common (40.3%), followed by central precocious puberty (CPP, 26.0%), gonadotropin (GnD; 20.4%), TSH (13.3%), and ACTH (13.3%) deficiencies. GHD increased with later treatment eras (P < .01), but replacement did not increase progression. CPP was associated with future GnD (P < .05). Posterior pituitary dysfunction (PPD; 7.2%) occurred in 57.9% after only biopsies or shunt procedures, and was associated with 6/13 deaths; 50.2% became obese. Tumor extent, surgery, and increased endocrinopathy, rather than radiotherapy, predicted visuocognitive morbidity.
  
  
  CONCLUSIONS
  This first longitudinal OP/HSG-specific study demonstrates that hypothalamo-pituitary dysfunction evolves hierarchically over decades. Tumor location predicts its speed of onset and radiotherapy its density. GnD can evolve from previous CPP, whereas life-threatening PPD can occur after any surgery. Our data suggest that recent radiation-avoiding chemotherapeutic strategies have increased GHD without improving survival.
authors.affiliation: Section for Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (H.-W.G.), University College London Institute of Child Health, London WC1N 1EH, United Kingdom; The London Center for Pediatric Endocrinology & Diabetes (H.-W.G., H.A.S.), Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, United Kingdom; Department of Neurosurgery (K.P., K.A., R.H.), Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, United Kingdom; and Children and Young People's Cancer Services (M.N.G.), University College London Hospitals NHS Foundation Trust, London NW1 2PG, United Kingdom.
authors.forename: Hoong-Wei
authors.initials: HW
authors.lastname: Gan
authors.affiliation: Section for Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (H.-W.G.), University College London Institute of Child Health, London WC1N 1EH, United Kingdom; The London Center for Pediatric Endocrinology & Diabetes (H.-W.G., H.A.S.), Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, United Kingdom; Department of Neurosurgery (K.P., K.A., R.H.), Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, United Kingdom; and Children and Young People's Cancer Services (M.N.G.), University College London Hospitals NHS Foundation Trust, London NW1 2PG, United Kingdom.
authors.forename: Kim
authors.initials: K
authors.lastname: Phipps
authors.affiliation: Section for Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (H.-W.G.), University College London Institute of Child Health, London WC1N 1EH, United Kingdom; The London Center for Pediatric Endocrinology & Diabetes (H.-W.G., H.A.S.), Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, United Kingdom; Department of Neurosurgery (K.P., K.A., R.H.), Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, United Kingdom; and Children and Young People's Cancer Services (M.N.G.), University College London Hospitals NHS Foundation Trust, London NW1 2PG, United Kingdom.
authors.forename: Kristian
authors.initials: K
authors.lastname: Aquilina
authors.affiliation: Section for Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (H.-W.G.), University College London Institute of Child Health, London WC1N 1EH, United Kingdom; The London Center for Pediatric Endocrinology & Diabetes (H.-W.G., H.A.S.), Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, United Kingdom; Department of Neurosurgery (K.P., K.A., R.H.), Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, United Kingdom; and Children and Young People's Cancer Services (M.N.G.), University College London Hospitals NHS Foundation Trust, London NW1 2PG, United Kingdom.
authors.forename: Mark Nicholas
authors.initials: MN
authors.lastname: Gaze
authors.affiliation: Section for Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (H.-W.G.), University College London Institute of Child Health, London WC1N 1EH, United Kingdom; The London Center for Pediatric Endocrinology & Diabetes (H.-W.G., H.A.S.), Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, United Kingdom; Department of Neurosurgery (K.P., K.A., R.H.), Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, United Kingdom; and Children and Young People's Cancer Services (M.N.G.), University College London Hospitals NHS Foundation Trust, London NW1 2PG, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Hayward
authors.affiliation: Section for Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Programme (H.-W.G.), University College London Institute of Child Health, London WC1N 1EH, United Kingdom; The London Center for Pediatric Endocrinology & Diabetes (H.-W.G., H.A.S.), Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, United Kingdom; Department of Neurosurgery (K.P., K.A., R.H.), Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, United Kingdom; and Children and Young People's Cancer Services (M.N.G.), University College London Hospitals NHS Foundation Trust, London NW1 2PG, United Kingdom.
authors.forename: Helen Alexandra
authors.initials: HA
authors.lastname: Spoudeas
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D004700:Endocrine System Diseases / Q000150:complications*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007027:Hypothalamic Diseases / Q000150:complications*; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D020339:Optic Nerve Glioma / Q000150:complications*