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This version published online on February 26, 2008
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2007-2294
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Submitted on October 15, 2007
Accepted on February 19, 2008

High prevalence of central adrenal insufficiency in patients with Prader-Willi syndrome

Roderick F.A. de Lind van Wijngaarde M.Sc.*, Barto J. Otten M.D., Ph.D., Dederieke A.M. Festen M.D., Koen F.M. Joosten M.D., Ph.D., Frank H. de Jong M.Sc., Ph.D., Fred C.G.J. Sweep M.Sc., Ph.D., and Anita C.S. Hokken-Koelega M.D., Ph.D.

Dutch Growth Research Foundation, Rotterdam, The Netherlands; Erasmus University Medical Center / Sophia Children's Hospital, Department of Pediatric Endocrinology, Rotterdam, The Netherlands; Radboud University Nijmegen Medical Center, Department of Pediatric Endocrinology, Nijmegen, The Netherlands; Erasmus University Medical Center / Sophia Children's Hospital, Department of Pediatric Intensive Care, Rotterdam, The Netherlands; Erasmus University Medical Center, Department of Internal Medicine, Laboratory of Endocrinology, Rotterdam, The Netherlands; Radboud University Nijmegen Medical Center, Department of Chemical Endocrinology, Nijmegen, The Netherlands

* To whom correspondence should be addressed. E-mail: r.delindvanwijngaarden{at}erasmusmc.nl; delind@kindengroei.nl.

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.
Key words: Prader-Willi syndrome • children • sudden death • adrenal insufficiency • metyrapone test • cortisol




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eLetters:

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Interpreting central adrenal insufficiency in PWS
Aaron L. Carrel, et al.
JCEM Online, 22 Jun 2008 [Full text]
Interpreting central adrenal insufficiency in PWS
Roderick F.A. de Lind van Wijngaarden, et al.
JCEM Online, 29 Aug 2008 [Full text]

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