The relationship between central adrenal insufficiency and sleep-related breathing disorders in children with Prader-Willi syndrome.
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.
de Lind van Wijngaarden
Roderick F A
RF
Dutch Growth Research Foundation, Erasmus University Medical Center/Sophia Children's Hospital, 3016 AH Rotterdam, The Netherlands. r.delindvanwijngaarden@erasmusmc.nl
Joosten
Koen F M
KF
van den Berg
Sandra
S
Otten
Barto J
BJ
de Jong
Frank H
FH
Sweep
C G J Fred
CG
de Weerd
Al W
AW
Hokken-Koelega
Anita C S
AC
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
D008797:Metyrapone