Evaluation of the hypothalamic-pituitary-adrenal axis and its relationship with central respiratory dysfunction in children with Prader-Willi syndrome Rare endocrinological diseases

Abstract

Background: Children with Prader-Willi Syndrome (PWS) have been considered at risk for central adrenal insufficiency (CAI). Hypothalamic dysregulation has been proposed as a common mechanism underlying both stress-induced CAI and central respiratory dysfunction during sleep. Objective: To evaluate CAI and sleep-related breathing disorders in PWS children. Patients and methods: Retrospective study of cortisol response following either insulin tolerance test (ITT) or glucagon test (GT) in 20 PWS children, and comparison with 33 non- Growth Hormone deficient (GHD) controls. Correlation between sleep related breathing disorders and cortisol response in 11 PWS children who received both investigations. Results: In PWS children, the cortisol peak value showed a significant, inverse correlation with age (Kendall's τ∈=∈-0.411; p∈=∈0.012). A similar though non-significant correlation was present between cortisol increase and age (τ∈=∈-0.232; p∈=∈0.16). Similar correlations were found in controls. In only 1 of 20 PWS children (5 %), ITT was suggestive of CAI. Four patients had an elevated central apnea index but they all exhibited a normal cortisol response. No relationship was found between peak cortisol or cortisol increase and central apnea index (respectively p∈=∈0.94 and p∈=∈0.14) or the other studied polysomnography (PSG) parameters. Conclusions: CAI assessed by ITT/GT is rare in PWS children. Our data do not support a link between CAI and central respiratory dysregulation.