de Lind van Wijngaarden RF et al. (2008) High prevalence of central adrenal insufficiency in patients with Prader–Willi syndrome. J Clin Endocrinol Metab [doi:10.1210/jc.2007-2294]

Prader–Willi syndrome (PWS) is a genetic disorder characterized by hypotonia, short stature, hyperphagia, obesity, hypogonadism, and delayed psychomotor development. The annual death rate in patients with PWS is ∼3% and many of these deaths are sudden and unexplained. Patients with PWS have hypothalamic dysregulation and de Lind van Wijngaarden et al. hypothesized that affected patients suffer from central adrenal insufficiency (CAI) during stressful conditions such as infections, which increases their risk of sudden death.

Metyrapone blocks cortisol synthesis and causes a sudden increase in demand for adrenocorticotropic hormone (ACTH) production, which mimics stress. The researchers performed a single-dose metyrapone test in 25 children with PWS who did not have any intercurrent illnesses at the time of the study. All patients (mean age 9.7 years) received metyrapone at 2330 h and fasting blood samples were taken for the analysis of ACTH, 11-deoxycortisol, cortisol and glucose at 0730 h the following day. In 16 of the 25 children, diurnal salivary cortisol profiles were also assessed.

The test results showed that 15 (60%) patients had an insufficient ACTH response and were, therefore, considered as having CAI during stressful conditions. Cortisol suppression did not differ between children with CAI and those without. All the children had normal diurnal rhythms of cortisol secretion.

The authors suggest that, unless CAI has been ruled out by a metyrapone test, hydrocortisone treatment should be considered in patients with PWS during stressful conditions.