The relationship between central adrenal insufficiency and sleep-related breathing disorders in children with Prader-Willi syndrome

J Clin Endocrinol Metab. 2009 Jul;94(7):2387-93. doi: 10.1210/jc.2008-2808. Epub 2009 Apr 21.

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.

Design: 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.

Setting: 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Insufficiency / complications*
  • Adrenal Insufficiency / diagnosis*
  • Adrenal Insufficiency / epidemiology
  • Child
  • Child, Preschool
  • Diagnostic Techniques, Endocrine
  • Female
  • Humans
  • Male
  • Metyrapone / pharmacology
  • Metyrapone / therapeutic use
  • Polysomnography
  • Prader-Willi Syndrome / complications*
  • Prader-Willi Syndrome / epidemiology
  • Sleep / drug effects
  • Sleep Apnea Syndromes / complications*
  • Sleep Apnea Syndromes / diagnosis
  • Sleep Apnea Syndromes / epidemiology

Substances

  • Metyrapone