The effects of 12 months of growth hormone replacement therapy on cardiac autonomic tone in adults with growth hormone deficiency

OBJECTIVES: Growth hormone deficiency (GHD) in adults is associated with a cluster of cardiovascular risk factors. Some abnormalities of cardiac structure and function have been reported in adult patients with GHD, but there are few data related to cardiac autonomic tone. Non-invasive assessment of cardiac autonomic status can be achieved by heart rate variability (HRV), which can be measured by using time-domain or frequency-domain variables. To our knowledge, short-term (6 months) effects of GH replacement therapy (GHRT) on HRV in a limited number of patients have been evaluated prospectively in only two previous studies. The present study was therefore designed to investigate the effects of GHD and 12 months of GHRT on cardiac autonomic tone in a larger number of adult patients with severe GHD. PATIENTS AND METHODS: HRV measurement, by using time-domain variables, was performed in 22 patients with GHD (eight men, 14 women; mean age 45.4 +/- 2.4 years) and 22 healthy controls (nine men, 13 women; mean age 40.8 +/- 1.8 years) at baseline. The time-domain variables (sympathetically influenced parameters SDNN and SDANN and parasympathetically influenced parameters RMSSD and PNN50) were derived from 24-h electrocardiogram (ECG) recordings. In the patient group, cardiac autonomic tone was re-evaluated after 6 and 12 months of GHRT. RESULTS: Mean baseline values of SDNN and SDANN were significantly higher (higher values mean lower sympathetic activity) in GHD patients than in healthy controls (P < 0.05), but mean baseline values of RMSSD and PNN50 did not differ significantly in healthy controls and patients. After 6 and 12 months of GHRT, mean SDNN and SDANN were decreased significantly when compared with the baseline values before GHRT (P < 0.05). However, mean RMSSD and PNN50 did not differ significantly from baseline. When SDNN and SDANN measurements were evaluated individually for each patient, after 12 months of GHRT both of the sympathetically influenced parameters decreased in 90% of the patients. CONCLUSIONS: These data indicate that sympathetic tone is decreased in adult patients with severe GHD. Additionally, an increment in sympathetic activity and normalization of sympathovagal balance have been demonstrated after 6 and 12 months of GHRT. This result suggests that, at least at the doses used in this study, GHRT improves sympathetic tone, without an obvious arrhythmogenic effect.