Abstract
ObjectiveAcromegaly is characterized by an excess of growth hormone (GH) and insulin like growth-factor 1 (IGF1), and it is strongly associated with cardiovascular diseases (CVD). Both acute and long-lasting pro-inflammatory effects have been attributed to IGF1. Previous results suggest the presence of systemic inflammation in treated patients. Here we assessed the association between treatment of acromegaly, systemic inflammation and vascular function. DesignEx vivo cytokine production and circulating inflammatory markers were assessed in peripheral blood from treated and untreated acromegaly patients (N = 120), and compared them with healthy controls. A more comprehensive prospective inflammatory and vascular assessment was conducted in a subgroup of six treatment-naive patients with follow-up during treatment. ResultsCirculating concentrations of VCAM1, E-selectin and MMP2 were higher in patients with uncontrolled disease, whereas the concentrations of IL18 were lower. In stimulated whole blood, cytokine production was skewed towards a more pro-inflammatory profile in patients, especially those with untreated disease. Prospective vascular measurements in untreated patients showed improvement of endothelial function during treatment. ConclusionsAcromegaly patients are characterized by a pro-inflammatory phenotype, most pronounced in those with uncontrolled disease. Treatment only partially reverses this pro-inflammatory bias. These findings suggest that systemic inflammation could contribute to the increased risk of CVD in acromegaly patients.
Highlights
Is a rare disease caused by excessive production of growth hormone (GH), mostly by a pituitary adenoma, and subsequent insulin-like growth factor 1 (IGF1) excess [1].GH and insulin like growth-factor 1 (IGF1) have numerous immunological, metabolic and cardiovascular effects [2,3,4,5].Patients with active acromegaly suffer from cardiovascular morbidity and mortality [6, 7]. the mortality risk practically normalizes with adequate treatment, cardiovascular disease (CVD) risk factors often persist [8]
Acromegaly patients that were admitted to the Cluj County Emergency Hospital (Cluj-Napoca, Romania) and nine healthy controls from this area, together with 71 treated patients from the Radboudumc and 41 healthy controls, who were described in our previous study [12]
There was no difference between the mean plasma IGF1 levels in controlled patients
Summary
Is a rare disease caused by excessive production of growth hormone (GH), mostly by a pituitary adenoma, and subsequent insulin-like growth factor 1 (IGF1) excess [1].GH and IGF1 have numerous immunological, metabolic and cardiovascular effects [2,3,4,5].Patients with active acromegaly suffer from cardiovascular morbidity and mortality [6, 7]. the mortality risk practically normalizes with adequate treatment, cardiovascular disease (CVD) risk factors often persist [8]. GH and IGF1 have numerous immunological, metabolic and cardiovascular effects [2,3,4,5]. Patients with active acromegaly suffer from cardiovascular morbidity and mortality [6, 7]. The mortality risk practically normalizes with adequate treatment, cardiovascular disease (CVD) risk factors often persist [8]. The mechanism underlying this phenomenon is not well understood; direct deleterious effects of GH and IGF1 on the cardiovascular and/or immune system have been suggested [9], but prospective systematic analyses are lacking. The CANTOS and COLCOT trials provided proofof-principle that targeting low-grade inflammation reduces cardiovascular events in high-risk patients [10, 11]
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