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The Endothelium in Acromegaly
Pietro Maffei1, Francesca Dassie1, Alexandra Wennberg2
1Clinica Medica 3, Department of Medicine (DIMED), Padua University Hospital, Padua, Italy.
Insights
Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) excess can cause endothelial dysfunction, impacting cardiovascular health in acromegaly patients. Further research is needed to understand this link fully.
Area of Science:
- Endocrinology
- Cardiovascular Medicine
- Vascular Biology
Background:
- Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) excess, as seen in acromegaly, are linked to cardiovascular complications.
- The endothelium plays a critical role in atherosclerosis and cardiovascular dysfunction, potentially serving as an early marker.
Purpose of the Study:
- To review the relationship between GH/IGF-1 excess and endothelial function.
- To explore mechanisms linking GH/IGF-1 excess to endothelial dysfunction and cardiovascular risk in acromegaly.
Main Methods:
- Review of basic science studies and clinical evidence on GH/IGF-1 excess and the endothelium.
- Examination of various arterial districts, including microvascular and major vessels.
- Analysis of preclinical markers of atherosclerosis and their relation to endothelial dysfunction.
Main Results:
- GH/IGF-1 excess promotes endothelial dysfunction through increased proliferation, impaired progenitor cells, oxidative stress, and reduced antioxidant defenses.
- These alterations are associated with atherosclerosis development in the general population.
- Preclinical atherosclerosis markers appear impaired in acromegaly, partly due to endothelial dysfunction, though the overall cardiovascular complication link remains debated.
Conclusions:
- Endothelial dysfunction is a significant consequence of GH/IGF-1 excess, mediated by multiple mechanisms.
- Understanding the pathophysiology of endothelial dysfunction in acromegaly is crucial for assessing cardiovascular disease risk.
- Further investigation is needed to fully elucidate the association between acromegaly, endothelial dysfunction, and cardiovascular complications.
Abstract:
Growth hormone (GH) and insulin like growth factor-1 (IGF-1) excess induce well-known deleterious effects on the cardiovascular system, especially after long-term exposition. Acromegaly, a condition of chronic GH and IGF-1 hypersecretion, is frequently associated to cardiovascular complications, although recent studies have shown a reduction in the prevalence of these comorbidities in well-controlled patients and a mortality risk similar to normal aging population. Many factors could contribute to the increased cardiovascular risk of acromegaly patients. Among these factors, the endothelium plays a key role in the pathogenesis of atherosclerotic plaques and could be considered an early marker of atherosclerosis and cardiovascular dysfunction. In this review we examined the relationship between GH/IGF-1 excess and the endothelium, from basic studies to clinical evidence. Many studies involving various arterial districts (microvascular arteries of retina, kidney and brain, and major vessels as carotid and aorta) showed that GH/IGF-1 excess promotes endothelial dysfunction via several different mechanisms. Increased endothelial proliferation, dysfunction of endothelial progenitor cells, increased oxidative stress, and compromised oxidative defenses are the main factors that are associated with endothelial dysfunction. In the general population, these alterations are associated with the development of atherosclerosis with an increased incidence of coronary artery disease and cerebrovascular complications. However, in acromegaly this is still a debated issue, despite the presence of many pro-atherogenic factors and comorbidities, such as hypertension, diabetes, sleep apnoea, and metabolic syndrome. Preclinical markers of atherosclerosis as arterial intima media thickness, pulse wave velocity and flow mediated dilation seem to be impaired in acromegaly and partly mediated by the endothelium dysfunction. In conclusion, the pathophysiology of endothelial dysfunction in the condition of GH and IGF-1 excess remains a crucial area of investigation to fully dissect the association of acromegaly with cardiovascular disease complications.
