title: The relationship between central adrenal insufficiency and sleep-related breathing disorders in children with Prader-Willi syndrome.
abstract: BACKGROUND
  The annual death rate of patients with Prader-Willi syndrome (PWS) is high (3%). Many deaths of children are sudden and unexplained. Sleep apneas have been suggested to play a role in sudden deaths. Recently, we discovered that 60% of patients with PWS suffer from central adrenal insufficiency (CAI) during stress.
  
  
  OBJECTIVE
  The aim was to study the relationship between CAI and sleep-related breathing disorders.
  
  
  METHODS
  In 20 children with PWS who underwent a metyrapone test (30 mg/kg at 2330 h), sleep-related breathing was evaluated by polysomnography before the metyrapone test. In addition, we recorded sleep-related breathing in 10 children with PWS during their metyrapone test. CAI was diagnosed when ACTH levels during the metyrapone test were below 33 pmol/liter at 0730 h. All tests were performed during healthy condition.
  
  
  METHODS
  The study was conducted in a pediatric intensive care unit and specialized sleep center.
  
  
  RESULTS
  Median (interquartile range) age was 8.4 yr (6.5-10.2). After metyrapone administration, median (interquartile range) central apnea index (number/hour) increased significantly from 2.2 (0.4-4.7) to 5.2 (1.5-7.9) (P = 0.007). The increase tended to be higher in children with CAI [2.8 (2.0-3.9) vs. 1.0 (-0.2 to 2.6); P = 0.09]. During polysomnography before the metyrapone test, sleep-related breathing was worse in children with CAI, who had a significantly higher central apnea index and tended to have a lower minimum oxygen saturation compared to those without CAI (P = 0.03 and P = 0.07).
  
  
  CONCLUSIONS
  In children with PWS, the central apnea index increased significantly after metyrapone administration, particularly in those with CAI during stress. In addition, children with CAI had a higher central apnea index compared to those without several months before the metyrapone test.
authors.affiliation: Dutch Growth Research Foundation, Erasmus University Medical Center/Sophia Children's Hospital, 3016 AH Rotterdam, The Netherlands. r.delindvanwijngaarden@erasmusmc.nl
authors.forename: Roderick F A
authors.initials: RF
authors.lastname: de Lind van Wijngaarden
authors.forename: Koen F M
authors.initials: KF
authors.lastname: Joosten
authors.forename: Sandra
authors.initials: S
authors.lastname: van den Berg
authors.forename: Barto J
authors.initials: BJ
authors.lastname: Otten
authors.forename: Frank H
authors.initials: FH
authors.lastname: de Jong
authors.forename: C G J Fred
authors.initials: CG
authors.lastname: Sweep
authors.forename: Al W
authors.initials: AW
authors.lastname: de Weerd
authors.forename: Anita C S
authors.initials: AC
authors.lastname: Hokken-Koelega
mesh_terms: D000309:Adrenal Insufficiency / Q000150:complications* / Q000175:diagnosis* / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D003940:Diagnostic Techniques, Endocrine; D005260:Female; D006801:Humans; D008297:Male; D008797:Metyrapone / Q000494:pharmacology / Q000627:therapeutic use; D017286:Polysomnography; D011218:Prader-Willi Syndrome / Q000150:complications* / Q000453:epidemiology; D012890:Sleep / Q000187:drug effects; D012891:Sleep Apnea Syndromes / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology
chemical_list: D008797:Metyrapone