Endocrine Abstracts

Adult growth hormone deficiency (GHD) is widely acknowledged for its association with heightened mortality, primarily linked to an increased risk of cardiovascular complications. Endothelin-1 (ET-1) is implicated in various cardiovascular conditions, including hypertension, atherosclerosis, and heart failure, where imbalances in its levels or signaling have been identified. Despite the distinct primary functions of growth hormone and endothelin within the body, both hormones assume a pivotal role in the intricate regulation of growth and developmental processes. Specifically, endothelin significantly contributes to the meticulous orchestration of blood flow regulation, exerting an indirect influence on the delivery of essential nutrients and oxygen to tissues. This intricate interplay carries profound implications for the sophisticated coordination of growth and metabolism within the organism. Furthermore, a critical non-traditional cardiovascular risk factor involves the heightened concentration of asymmetric dimethylarginine (ADMA), a potent inhibitor of nitric oxide synthase that contributes to vascular endothelial dysfunction. Elevated ADMA levels coincide with increased vascular tension, higher blood pressure, and the activation of numerous pro-atherogenic mechanisms. These include platelet aggregation, monocyte adhesion, smooth muscle cell proliferation, extracellular matrix expansion, and lipid accumulation in macrophages - elements that collectively contribute to the development of atherosclerosis. Consequently, this study aims to evaluate the effectiveness of recombinant human growth hormone (rhGH) in mitigating levels of ET-1 and ADMA in patients with GHD. The study focuses on assessing the efficacy of rhGH therapy in enhancing levels of ET-1 and reducing ADMA. The study encompassed 10 patients diagnosed with GHD who underwent a 12-month course of rhGH therapy. Measurements of ET-1 and ADMA levels were taken prior to the commencement of the therapy, at the 6-month mark, and at the conclusion of the 12-month period. Statistical analysis involved repeated-measures ANOVA and post hoc tests with Bonferroni correction.

Results: After 12 months of rhGH therapy, a significant decrease in the levels of ET-1 (P=0.04) was observed. Additionally, a statistically significant negative correlation between IGF-1 and ADMA levels were observed both after 6 and 12 months of therapy (r=-0.65, P=0.02; R-0.65, P=0.01, respectively). Post hoc tests confirmed significant differences between individual observation periods. The findings of this research suggest a potential link between growth hormone replacement therapy and a reduction in cardiovascular risk through its impact on ET-1 and ADMA levels. These results have the potential to contribute to the improvement of rhGH replacement therapy protocols, exerting a broader influence on the cardiovascular well-being of individuals undergoing such interventions.