Improvement of Endothelial Dysfunction in Acromegaly after Transsphenoidal Surgery

Abstract

Abstract. Flow-mediated vasodilatation (FMD) is a vascular functional test to detect endothelial dysfunction at the early stage of cardiovascular diseases. Patients with active acromegaly have higher morbidity and mortality due to cardiovascular events. To determine whether active acromegaly is associated with endothelial dysfunction, we studied 17 patients with active acromegaly for measurements of FMD, carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV), and other biochemical parameters before and 3 months after transsphenoidal surgery (TSS). Baseline %FMD in patients with active acromegaly was significantly lower than that in age-and sex-matched control subjects. After TSS, the mean %FMD in acromegaly significantly increased from 5.3% to 7.4%; 12 patients had increased %FMD (responders), whereas 5 patients had decreased or unchanged %FMD (non-responders). However, neither carotid IMT nor baPWV changed after TSS. Serum levels of GH, insulin-like growth factor (IGF)-1, total cholesterol, lowdensity lipoprotein cholesterol (LDL-C), hemoglobin HA1C, fasting plasma glucose and insulin levels, and homeostasis model assessment (HOMA)-R significantly decreased, whereas high-density lipoprotein cholesterol significantly increased. Responders had significantly lower baseline %FMD than did non-responders and both insulin levels and HOMA-R significantly decreased in responders, but not in non-responders after TSS. Simple regression analysis revealed that the change of %FMD showed a significant negative correlation with that of LDL-C, but not of IGF-1 or GH, in responders. In conclusion, it is suggested that endothelial dysfunction associated with active acromegaly improves soon after TSS, which is related to LDL-C and/or insulin resistance, but not to excess GH and/or IGF-1 itself.

Ambulatory arterial stiffness indexes in acromegaly

“…Smith et al (12) observed an increased augmentation index (a measure of arterial stiffness) in 16 NOR-ACRO, when compared with healthy controls, with a partial reduction after 3 months of GH suppression therapy. Sakai et al (13) reported no change in pulse wave velocity (a different measure of arterial stiffness) in patients with active acromegaly after transsphenoidal surgery, despite improved endothelium-mediated dilation. More recently, Paisley et al (14) reported a significantly increased pulse wave velocity but unaltered intima-media thickness in 56 patients with acromegaly when compared with controls, considering this phenomenon as a pressure-related stiffening of the arterial wall.…”

“…Few studies have focused on arterial stiffness in acromegaly, all using pulse wave analysis, with contrasting results (12,13,14). The aim of our study was to investigate arterial stiffness using the ambulatory arterial stiffness index (AASI) and symmetric AASI (Sym-AASI), two indexes derived from 24 h ambulatory blood pressure monitoring (ABPM) (15,16), in a group of normotensive and hypertensive patients with active acromegaly, compared with normotensive controls (NOR-CTR) or hypertensive controls (HYP-CTR).…”

The assessment of total antioxidant capacity and superoxide dismutase levels, and the possible role of manganese superoxide dismutase polymorphism in acromegaly

“…These studies demonstrated that flow-mediated dilatation and endothelial cell markers were significantly lower in uncontrolled and also controlled acromegaly patients than healthy subjects [2,21]. In another study, it was also shown that impaired carotid intima-media thickness and brachial-ankle pulse wave velocity could persist after transsphenoidal surgery [22]. Present study showed that although the levels of SOD and TAC were higher in controlled acromegaly patients than those with uncontrolled disease activity, uncontrolled and also controlled acromegaly patients had the decreased levels of SOD and TAC compared to healthy subjects.…”

Association of serum IGF1 with endothelial function: results from the population-based study of health in Pomerania

“…Since the authors did not present data analysis separately for men (nZ65) and women (nZ35), it cannot be excluded that the observed association of IGF1 levels and acetylcholine-induced forearm blood flow in their whole population was due to the preponderance of male subjects. Other studies focussing on the relationship of serum IGF1 levels and endothelial function were even smaller and primarily confined to patients with disturbed GH secretion, such as acromegaly or GH deficiency (15)(16)(17). In patients with low (15,16) and high (17) preinterventional serum IGF1 levels, normalization of IGF1 levels led to an improvement of previously reduced FMD.…”

“…In patients with low serum IGF1 levels due to GH deficiency, substitution of GH leads to normalization of a previously reduced FMD (15,16). On the other hand, in acromegaly patients with high IGF1 levels, surgical resection of the GH-producing tumor was followed by an improvement of previously reduced FMD (17). More recently, an association between serum IGF1 levels and the acetylcholine-stimulated increase of forearm blood flow, as measured by plethysmography, was described in a population of 100 untreated hypertensive patients (18).…”