Normal cortisol response on low-dose synacthen (1 microg) test in children with Prader Willi syndrome.

Abstract

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. 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 T4. 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 μg Synacthen. Post-Synacthen cortisol levels were measured at 30 min, and a cortisol level above 500 nmol/liter was considered normal. 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%. Our result suggests that CAI is rare in children with PWS.