Background: Poor temperature regulation in PraderWilli syndrome (PWS) suggests dysautonomia probably secondary to hypothalamic dysfunction. Autonomic nervous system (ANS) has control over orexigenic ghrelin.
Objective and hypotheses: We aim to assess ANS function in PWS and its association with acyl ghrelin.
Method: We recruited 16 genetically-confirmed children with PWS and 16 controls. Exclusion criteria were diabetes mellitus, psycho-trophic medications, and other hypothalamic pathologies. Subsidized GH therapy for children with PWS became available before the study and became an unavoidable confounder for the study. We performed a mixed meal study to assess ANS and ghrelin statuses. Orthostatic change in pulse rate (PR), and blood pressure (BP) expressed as per cent change of PR (%ΔPR), BP (%ΔBP) were used to access ANS function. PR and BP increase soon after standing from recumbent position by increasing sympathetic vasomotor tone. Sympathetic and parasympathetic nervous systems are stimulated after a meal. We examined %ΔPR and %ΔBP at 15 and 30 s after standing from a lying, at fasting, and post-prandial periods. We measured plasma gastrin, catecholamines (Pcat) and urinary catecholamines (Ucat) to complement cardiovascular data.
Results: Post-prandial %ΔPR at both 15 and 30 s were significantly lower in PWS group than controls. %Δ systolic BP and diastolic BP were not different in both groups. Post-prandial plasma gastrin and Ucat were higher in PWS group than controls but Pcat were not different in two groups. Fasting plasma acyl ghrelin (AG) was higher in PWS but it decreased to similar level of controls at 120 min after a meal. Fasting AG is negatively correlated to fasting %ΔPR at 30 s (r=−0.52, P=0.04).
Conclusion: In PWS, there is measureable sympathetic dysfunction indicated by poor orthostatic pulse change. Higher gastrin and Ucat suggest poor vagal function similar to post-vagotomy state. Because of ANS dysfunction, fasting ghrelin was high.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology