Biochemical and Biophysical Markers of Endothelial Dysfunction in Adults with Hypopituitarism and Severe GH Deficiency

Abstract

Adult hypopituitarism is known to be associated with reduced life expectancy related to excess vascular events, and endothelial dysfunction is present in patients with this condition. We studied the relationship between biophysical and biochemical markers of endothelial dysfunction, including E-selectin, intercellular cell adhesion molecule-1, von Willebrand factor, and thrombomodulin in 52 adult patients with hypopituitarism and severe GH deficiency (<2 ng/ml on provocative testing) compared with 54 age-, sex-, and smoking-matched normal controls. We also examined endothelium-dependent dilatation of the brachial artery to postischemic occlusion and carotid artery morphology (intima-media thickness) by high-resolution ultrasonography. The patients were stable on conventional hormone replacement therapy but not on GH therapy, and none of the subjects had a known risk factor for vascular disease. Levels of E-selectin [57 +/- 3 vs. 49 +/- 2 ng/ml (mean +/- SEM)] (P < 0.043), intercellular cell adhesion molecule-1 (308 +/- 11 vs. 266 +/- 10 ng/ml) (P < 0.001), thrombomodulin (49 +/- 3 vs. 35 +/- 2 ng/ml) (P < 0.001), and von Willebrand factor (132 +/- 7% vs. 105 +/- 5%) (P < 0.004) were significantly higher in patients than in controls. Brachial artery endothelium-dependent dilatation was significantly lower in patients than in controls [4.7% (0.00-9.77) vs. 10.5% (6.4-16.2) (median, interquartile range)] (P < 0.001). This difference in endothelium-dependent dilatation was more marked in female patients than in controls (P < 0.003), although it disappeared when estrogen-sufficient female patients were compared with controls (P = 0.31). However, the female patients who were not replaced with estrogen continued to show a striking difference compared with estrogen-deficient control females (P < 0.004). There was no difference in carotid intima-media thickness between patients of either sex and controls. On univariate analysis, brachial artery endothelium-dependent dilatation correlated inversely with intercellular cell adhesion molecule-1 (r = -0.225, P < 0.033). Intercellular cell adhesion molecule-1 correlated positively with E-selectin (r = 0.466, P < 0.0001) and negatively with IGF-I (r = -0.238, P < 0.016). E-selectin correlated with thrombomodulin (r = 0.215, P < 0.034) and von Willebrand factor (r = 0.218, P < 0.03) and negatively with IGF-I (r = -0.255, P < 009). Thrombomodulin correlated positively with von Willebrand factor (r = 0.422, P < 0.0001) and inversely with IGF-I (r = -0.266, P < 0.008). These correlations persisted after correction for age, sex, body mass index, and waist to hip ratio, with the exception of IGF-I, which now correlated with thrombomodulin only. These results confirm significant endothelial dysfunction in hypopituitarism and provide insight into the relationship of biochemical and biophysical markers of early atherosclerosis in hypopituitary GH-deficient adults. The negative correlation of IGF-I with some biochemical markers of endothelial dysfunction and the predictive nature of GH de...

Inflammatory and endothelial markers during the menstrual cycle

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Hemostatic abnormalities in endocrine and metabolic disorders

“…A very small number of case-control studies suggested the presence of a mild to moderate prothrombotic state in adult patients with GH deficiency, which could partly contribute to the increased risk for arterial and venous thrombosis seen in hypopituitarism (88)(89)(90)(91). Increased circulating levels of VWF, thrombomodulin, and some endothelial adhesion molecules (such as intercellular adhesion molecule-1 and E-selectin) were observed by Elhadd et al in 52 GH-deficient adults (91).…”

Growth Hormone Treatment during Hemodialysis in a Randomized Trial Improves Nutrition, Quality of Life, and Cardiovascular Risk

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