High prevalence of central adrenal insufficiency in patients with Prader-Willi syndrome.
BACKGROUND
The annual death rate of Prader-Willi syndrome (PWS) patients is very high (3%). Many of these deaths are sudden and unexplained.


OBJECTIVE
Because most deaths occur during moderate infections and PWS patients suffer from various hypothalamic insufficiencies, we investigated whether PWS patients suffer from central adrenal insufficiency (CAI) during stressful conditions.


METHODS
Overnight single-dose metyrapone tests were performed. Metyrapone (30 mg/kg) was administered at 2330 h. At 0400, 0600, and 0730 h, ACTH, 11-deoxycortisol, cortisol, and glucose levels were measured. Diurnal salivary cortisol profiles were assessed on a different day at wake-up, 30 min after wake-up, at 1400 h, and at 2000 h.


METHODS
The study was conducted in a pediatric intensive care unit.


METHODS
Patients included 25 randomly selected PWS patients.


METHODS
Patients were considered as having CAI when ACTH levels remained below 33 pmol/liter at 0730 h.


RESULTS
Median (interquartile range) age was 9.7 (6.8-13.6) yr. Fifteen patients (60%) had an insufficient ACTH response (CAI, P < 0.001). There was no significant difference in age, gender, genotype, and body mass index SD score between patients with CAI and those without. Morning salivary cortisol levels and diurnal profiles were normal in all children, suggesting that CAI becomes apparent only during stressful conditions.


CONCLUSIONS
Strikingly, 60% of our PWS patients had CAI. The high percentage of CAI in PWS patients might explain the high rate of sudden death in these patients, particularly during infection-related stress. Based on our data, one should consider treatment with hydrocortisone during acute illness in PWS patients unless CAI has recently been ruled out with a metyrapone test.
de Lind van Wijngaarden
Roderick F A
RF
Dutch Growth Research Foundation and Erasmus University Medical Center/Sophia Children's Hospital, Westzeedijk 106, Rotterdam, The Netherlands. r.delindvanwijngaarden@erasmusmc.nl
Otten
Barto J
BJ
Festen
Dederieke A M
DA
Joosten
Koen F M
KF
de Jong
Frank H
FH
Sweep
Fred C G J
FC
Hokken-Koelega
Anita C S
AC
D000293:Adolescent; D000309:Adrenal Insufficiency / Q000453:epidemiology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D001794:Blood Pressure; D002648:Child; D002675:Child, Preschool; D002940:Circadian Rhythm; D019382:Human Growth Hormone / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008797:Metyrapone; D011218:Prader-Willi Syndrome / Q000150:complications*; D015995:Prevalence
D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone; D008797:Metyrapone