SAT-380 Screening for Central Adrenal Insufficiency in Children with Prader-Willi Syndrome (PWS) with Single Collection Of ACTH and Cortisol Levels

Abstract

Baseline a.m ACTH and Cortisol levels in Children with Prader-Willi-syndrome are no different from general population. Moris Angulo, MD1 & Mariano Castro-Magaña, MD1 1Dept of Peds, NYU-Winthrop Hospital, New York, NY Background Prader-Willi syndrome (PWS) is a multi-system genetic disorder resulting from the lack of expression of the paternal genes from chromosome 15q11.2-q13 due to paternal deletion, uniparental disomy (UPD) or an imprinting center defect. Many of their features are explained by hypothalamic dysfunction, therefore individuals with PWS are at high risk for pituitary hormonal deficiency. When the pituitary begins to fail, there is generally a specific sequential failure of pituitary hormones, starting with GH, continuing through LH and FSH deficiency, and culminating in loss of TSH and ACTH. Generally, ACTH is the last to be lost. A high prevalence (60%) of central adrenal insufficiency (CAI) however, has been reported in Prader-Willi syndrome (PWS) using the metyrapone test. Many children, including infants have undergone stimulation testing to confirm or rule out CAI. Several studies however, using same test and other different testing methods including insulin tolerance test (ITT), low dose/high dose ACTH stimulation, glucagon stimulation tests have reported differing results with prevalence between 0 to 7·5%. Previous study has shown that basal cortisol is closely correlated with adrenal response to stimulation. Methods: We studied 105 children with genetic diagnosis of PWS, age 2 to__years. (60 males and 45 females) after basal Cortisol and ACTH level collected at 0800 h. Sixty eight children (60 %) had deletion I and II, 24 (23%)UPD and 13 had only positive DNA Methylation testing . All participant were already on GH treatment without illness or any other stressful condition during testing. Results: All had normal morning Cortisol and ACTH level but 2 children, age 2 and 5 years with low and 4 y.o. male with increased cortisol level. These 3 children had normal ACTH level. Repeat sample after a week, revealed normal both Cortisol and ACTH level. Conclusion: suggesting that clinically significant adrenal insufficiency in PWS is rare