Growth Hormone Treatment, Cardiovascular Risk and Autonomic Maturation in Children and Adolescents with Growth Hormone Deficiency or Born Small for Gestational Age

Abstract

Introduction: The impact of growth hormone therapy in children with short stature on cardiovascular prognosis seems to be unpredictable from big databases. The enhanced cardiovascular risk in this group of patients may be related to adverse autonomic imprinting by early life stress. Autonomic dysfunction and possible effects of growth hormone therapy on the autonomic nervous system can be measured easily by calculating heart rate variability (HRV) from Holter electrocardiogram monitoring. Methods: We performed HRV analysis prior to growth hormone therapy (N = 33), within the first year of growth hormone therapy between 4 and 10 years of age (N = 19), at least a further HRV measurement between 10 and 15 years (N = 30). Additional measurements were performed before and after cessation of growth hormone therapy (N = 14). Data were compared to untreated pediatric patients with short stature and to age matched healthy controls. Results: Untreated patients with short stature due to growth hormone deficiency or intrauterine growth restriction in early childhood have significantly increased heart rates most of all at night and concomitantly reduced global HRV indicated as Standard Deviation of Normal to Normal Intervals (SDNN). Growth hormone treated adolescents and the untreated patients with short stature show significantly elevated mean heart rates and concomitantly reduced vagus activities measured as reduced Route Mean Square Standard Deviation (RMSSD). After cessation of growth hormone treatment SDNN significantly increases and heart rate decreases to normal values in formerly treated patients with catch-up growth. Conclusion: There is a comparable autonomic dysfunction in treated and untreated children with short stature as an indicator for enhanced cardiovascular risk. After cessation of growth hormone therapy, we found a significant improvement of reduced HRV to normal values.