Normal Cortisol Response on Low-Dose Synacthen (1 μg) Test in Children with Prader Willi Syndrome

Introduction: It has been postulated that central adrenal insufficiency (CAI), resulting from hypothalamic dysfunction, may contribute to the increased unexplained death rates in Prader Willi syndrome (PWS). A study using the overnight metyrapone test reported a 60% prevalence of CAI in children with PWS. We used a low-dose Synacthen test to screen for CAI in children with PWS. Methods: We studied 41 children with genetic diagnosis of PWS [20 males; mean age, 7.68 (+/- 5.23) yr] in five pediatric endocrinology centers in Australasia. All participants were randomly selected, and none had a history of Addisonian crisis. Ten of the cohort were receiving sex hormone therapy, 19 were receiving GH, and four were receiving T-4. Their mean body mass index z-score was +/- 1.48 (+/- 1.68). Baseline morning ACTH and cortisol levels were measured, followed by iv administration of 1 mu g Synacthen. Post-Synacthen cortisol levels were measured at 30 min, and a cortisol level above 500 nmol/liter was considered normal. Results: The mean baseline ACTH and cortisol were 15 (+/- 14) ng/liter and 223 (+/- 116) nmol/liter, respectively. The mean 30-min plasma cortisol was 690 (+/- 114) nmol/liter, and the average increase from baseline was 201%. Conclusions: Our result suggests that CAI is rare in children with PWS. (J Clin Endocrinol Metab 95: E464-E467, 2010)