title: Prevalence and risk factors of radiation-induced growth hormone deficiency in childhood cancer survivors: a systematic review.
abstract: BACKGROUND
  Growth hormone deficiency (GHD) is usually the first and most frequent endocrine problem occurring after cranial radiotherapy (CRT). The aim of this systematic review was to evaluate the existing evidence of the prevalence and risk factors of radiation-induced GHD in childhood cancer survivors.
  
  
  METHODS
  MEDLINE, EMBASE and CENTRAL were searched for studies reporting on radiation-induced GHD in childhood cancer survivors. Information about study characteristics, prevalence and risk factors was abstracted and the quality of each study was assessed. A meta-regression analysis was performed.
  
  
  RESULTS
  The prevalence of radiation-induced GHD was estimated in 33 studies. Most studies had methodological limitations. The prevalence varied considerably between 0% and 90.9%. Selecting only the studies with adequate peak GH cut-off limits (<5 microg/L) resulted in 3 studies. In these studies the prevalence ranged from 29.0% to 39.1%, with a pooled prevalence of 35.6%. Higher CRT dose and longer follow-up time have been suggested to be the main risk factors of GHD by studies included in this review. The meta-regression analysis showed that the wide variation in the prevalence of GHD could be explained by differences in maximal CRT dose.
  
  
  CONCLUSIONS
  GHD is a frequent consequence after CRT in childhood cancer survivors. The prevalence of radiation-induced GHD ranged from 29.0% to 39.1% when selecting only studies with adequate peak GH cut-off limits. Higher CRT dose and longer follow-up time are the main risk factors. More well-designed studies are needed to accurately estimate the prevalence of GHD and to define the exact CRT threshold dose.
authors.affiliation: Department of Paediatric Oncology, Emma Children's Hospital/Academic Medical Center, F8 Noord, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands. r.l.mulder@amc.uva.nl
authors.forename: Renée L
authors.initials: RL
authors.lastname: Mulder
authors.forename: Leontien C M
authors.initials: LC
authors.lastname: Kremer
authors.forename: Hanneke M
authors.initials: HM
authors.lastname: van Santen
authors.forename: Jan Lucas
authors.initials: JL
authors.lastname: Ket
authors.forename: A S Paul
authors.initials: AS
authors.lastname: van Trotsenburg
authors.forename: Caro C E
authors.initials: CC
authors.lastname: Koning
authors.forename: Antoinette Y N
authors.initials: AY
authors.lastname: Schouten-van Meeteren
authors.forename: Huib N
authors.initials: HN
authors.lastname: Caron
authors.forename: Sebastian J C M M
authors.initials: SJ
authors.lastname: Neggers
authors.forename: Elvira C
authors.initials: EC
authors.lastname: van Dalen
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D009369:Neoplasms / Q000532:radiotherapy*; D015995:Prevalence; D011832:Radiation Injuries / Q000209:etiology* / Q000378:metabolism*; D011878:Radiotherapy / Q000009:adverse effects; D012307:Risk Factors; D017741:Survivors; D055815:Young Adult
chemical_list: D019382:Human Growth Hormone