Context The annual death rate of 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 if PWS patients suffer from central adrenal insufficiency (CAI) during stressful conditions.

Design Overnight single-dose metyrapone tests were performed. Metyrapone (30 mg/kg) was administered at 2330 h. At 0400, 0600 h 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 minutes after wake-up, 1400 h and 2000 h.

Setting Pediatric Intensive Care Unit.

Patients 25 randomly selected PWS patients.

Main outcome measure Patients were considered as having CAI when ACTH levels remained below 33 pmol/l at 0730 h.

Results Median (inter-quartile range) age was 9.7 (6.8–13.6) years. Fifteen patients (60%) had an insufficient ACTH response (CAI, p<0.001). There was no significant difference in age, gender, genotype and BMI SDS 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 central adrenal insufficiency. 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.