Elevated plasma endothelin as an additional cardiovascular risk factor in patients with Cushing's syndrome

Abstract

Background: Recently the pathophysiological role of endothelin (ET) has been presumed in a number of adrenal disorders such as primary hyperaldosteronism, pheochromocytoma and adrenocortical insufficiency. Aim: The aim of the present study was to evaluate circulating ET-1 levels in patients with endogenous Cushing's syndrome. Methods and results: Plasma ET-1 levels were determined by highly sensitive RIA. Thirteen untreated subjects with Cushing's syndrome were studied: eight women and five men of mean age 44.2^9.5 years (S.D.). In ten of them, Cushing's disease had been diagnosed and three had adrenal adenomas. ET-1 was 3-fold higher in the patient group than in age-matched healthy controls (n ¼ 13): 1.59^0.78 vs 0.46^0.20 pmol/l respectively, P , 0.001. In adrenal adenoma patients, ET-1 was not significantly higher than in the Cushing's disease subjects (1.84^0.67 vs 1.51^0.83 pmol/l respectively, P . 0.05). In three patients who died of severe cardiovascular complications, plasma ET-1 was significantly higher than in the remaining patients (2.34^0.35 pmol/l, P , 0.05). A positive correlation was found between the total cholesterol (6.94^1.75 mmol/l) and ET-1 levels in the patients with Cushing's syndrome: r ¼ þ0.73, P , 0.02. No correlation was observed, however, between the levels of ET-1 and blood pressure (183^37/106^18 mmHg), plasma cortisol levels (455.2^74.5 nmol/l) or urinary cortisol excretion (1463^726 nmol/24 h). The successful treatment and correction of hypercortisolism in seven patients led to insignificant reduction in plasma ET from 1.34^0.69 to 0.73^0.53 pmol/l, P . 0.05. Conclusion: Our results clearly demonstrate that the ET system is activated in Cushing's syndrome. Elevated plasma ET-1 levels probably play a role in the pathogenesis of accelerated and early atherosclerosis development in this disorder.

Cushing's disease and hypertension: in vivo and in vitro study of the role of the renin-angiotensin-aldosterone system and effects of medical therapy

“…This observation contrasts to the reported decrease in ET-1 concentration, although not statistically significant, after successful surgery for CS (34). This discrepancy may be explained by different follow-up periods or, although speculative, by direct effects of our study medication.…”

Antenatal Corticosteroids Impact the Inflammatory Rather Than the Antiangiogenic Profile of Women With Preeclampsia

“…For example, ET-1 is known to increase in response to hypercortisolism (ie, Cushing syndrome). 42 In this condition, the changes in ET-1 concentrations vary independently of hypertension. This paradox was previously attributed to the complex pathogenesis of the syndrome and to the observation that circulating ET-1 may not reflect tissue or endothelial ET-1 levels.…”

Metabolic comorbidities in Cushing's syndrome

“…GC-induced increase of erythropoietin contributes to vasoconstriction and therefore hypertension (162). Endothelin has been found to be increased in CS patients (163). This increase could be related to the GC excess-induced endothelial damage and increased vascular permeability, causing endothelin hypersecretion in the circulation with the consequent permissive effect on the atherogenic and pressor action of endothelin.…”