title: Time Dependence of Radiation-induced Hypothalamic-Pituitary Axis Dysfunction in Adults Treated for Non-pituitary, Intracranial Neoplasms.
abstract: Hypothalamic-pituitary axis (HPA) dysfunction is a sequela of cranial radiotherapy. The purpose of this study was to use endocrine data from existing publications to characterise the baseline endocrine status, the effects of radiotherapy on the HPA during the first follow-up year and the time dependence of radiation-induced HPA dysfunction in patients treated with radiotherapy for non-pituitary intracranial neoplasms.
  
  
  
  A systematic search of databases was carried out for articles that reported the results of endocrine testing for patients aged 16 years and older who were treated with neurosurgery for non-pituitary intracranial neoplasms or radiotherapy for nasopharyngeal neoplasms. To analyse the radiotherapy-related changes in hormone levels over time, long-term prospective endocrine data from nasopharyngeal studies were normalised to baseline hormone data and fitted to an exponential decay model. This process was repeated with normalisation to year 1 hormone data.
  
  
  
  Eight unique articles met eligibility criteria. HPA dysfunction occurred in 21.6-64.7% of patients who were assessed for endocrinopathies following neurosurgery. Studies on the early effects of radiotherapy on nasopharyngeal patients showed statistically significant changes in growth hormone, luteinizing hormone and follicle stimulating hormone levels during the first year of follow-up. Time dependence modelling showed that normalisation to year 1 hormone levels yield exponential equations with stronger measures of goodness of fit.
  
  
  
  HPA dysfunction in patients treated for non-pituitary intracranial neoplasms is probably a result of both neurosurgery and radiotherapy treatments. Although statistically significant endocrine changes can occur during this first year of follow-up, those documented at year 1 may be more predictive of subsequent HPA dysfunction.
authors.affiliation: Cancer Research UK VoxTox Research Group, University of Cambridge Department of Oncology, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, UK; University of Cambridge Department of Oncology, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: N
authors.initials: N
authors.lastname: Taku
authors.affiliation: Cancer Research UK VoxTox Research Group, University of Cambridge Department of Oncology, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, UK; Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge and National Institute for Health Research Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: M
authors.initials: M
authors.lastname: Gurnell
authors.affiliation: Cancer Research UK VoxTox Research Group, University of Cambridge Department of Oncology, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, UK; University of Cambridge Department of Oncology, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: N
authors.initials: N
authors.lastname: Burnet
authors.affiliation: Cancer Research UK VoxTox Research Group, University of Cambridge Department of Oncology, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, UK; University of Cambridge Department of Oncology, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, UK. Electronic address: rjena@nhs.net.
authors.forename: R
authors.initials: R
authors.lastname: Jena
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000532:radiotherapy*; D016371:Cranial Irradiation / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007027:Hypothalamic Diseases / Q000453:epidemiology / Q000209:etiology*; D007030:Hypothalamo-Hypophyseal System / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000528:radiation effects*; D013997:Time Factors
keywords: Hypopituitarism; non-pituitary intracranial neoplasms; pituitary insufficiency; radiotherapy