endothelin-1 and Adenoma

Recently the pathophysiological role of endothelin (ET) has been presumed in a number of adrenal disorders such as primary hyperaldosteronism, pheochromocytoma and adrenocortical insufficiency.. The aim of the present study was to evaluate circulating ET-1 levels in patients with endogenous Cushing's syndrome.. 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=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=+0.73, 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.. 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.

Topics: Adenoma; Adrenal Gland Neoplasms; Adult; Cardiovascular Diseases; Cushing Syndrome; Endothelin-1; Female; Humans; Hydrocortisone; Male; Matched-Pair Analysis; Middle Aged; Reference Values; Risk Factors

Endothelin-1 (ET-1) may function as an aldosterone secretagogue and, in turn, aldosterone can upregulate ET-1 expression. Hence, the existence of a feedforward loop involving ETs and aldosterone has been speculated in primary aldosteronism (PA). In the present study, we sought to examine ET-1 secretion from the adrenal glands in patients with PA.. We determined ET-1 levels in blood samples obtained during adrenal venous sampling of patients affected by PA (n=17). Furthermore, we examined the mRNA expression of the ET system in tissue samples from aldosterone-producing adenomas (APAs, n=9) and control normal adrenals (n=3).. Blood ET-1 levels were determined by RIA. Tissue mRNA expression of the ET system was assayed with Affymetrix microarrays.. ET-1 levels did not differ between inferior vena cava and adrenal vein blood in both bilateral adrenal hyperplasia and APA patients. Moreover, cortisol-normalized ET-1 levels did not show lateralized adrenal ET-1 secretion in APAs. Through gene expression profiling with microarray performed in a distinct set of APA individuals (n=9), we confirmed the adrenal expression of a complete ET system, but we did not detect a significant upregulation of ET components within the APA tissue compared with normal adrenals.. The present data argue against the hypothesis of increased ET-1 secretion from APAs and do not support a general role for adrenal ET-1 in the vascular pathophysiology of PA.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenal Glands; Aged; Aldosterone; Aspartic Acid Endopeptidases; Endothelin-1; Endothelin-Converting Enzymes; Female; Humans; Hyperaldosteronism; Male; Metalloendopeptidases; Middle Aged; Receptor, Endothelin A; Receptor, Endothelin B; RNA, Messenger

Endothelins (ETs) are 21 amino acid peptides with vasoactive and mitogenic properties. The three isopeptides (ET-1, -2, and -3) and their receptors (E1A and ETB subtypes) display expression in numerous tissues and possibly mediate autocrine/paracrine actions. The present investigation shows that ET-1 triggers biphasic increases of the concentration of cytoplasmic Ca2+ ([Ca2+]i) in pathological human parathyroid cells. Both the peak and sustained [Ca2+]i increase, as well as the proportion of responding cells, are dose-dependent in the 10(-10)-10(-7) mol/L range of ET-1. In absence of external Ca2+, the ET-1-induced [Ca2+]i peak is attenuated. ET-3 has no effect on [Ca2+]i indicating functional dominance of the ETA receptor subtype. ET-1 (10 nmol/L) lowers parathyroid hormone secretion in 0.5 mmol/L but not in higher external Ca2+ concentrations, and parathyroid cell ET release is inhibited by increases of external Ca2+. Fibroblasts overgrowing the parathyroid chief cells during monolayer culture respond to ET-1 with biphasic [Ca2+]i increases or repetitive [Ca2+]i spikes, but show no response to elevation of external Ca2+. These findings imply that ET secretion and ET receptor expression may constitute an autocrine/paracrine mechanism in the regulation of human PTH secretion.

Topics: Adenoma; Calcium; Cells, Cultured; Endothelin-1; Endothelin-3; Epithelial Cells; Fibroblasts; Humans; Hyperparathyroidism; Hyperplasia; Multiple Endocrine Neoplasia Type 1; Parathyroid Glands; Parathyroid Hormone; Parathyroid Neoplasms; Signal Transduction; Tumor Cells, Cultured

The aim of the study was to evaluate possible changes of plasma endothelin-1 levels (ET-1) in patients with hypertension secondary to primary aldosteronism and pheochromocytoma. We enrolled in the study: 12 patients affected by aldosterone-producing adenoma (5 M and 7 W; mean age 42.1 +/- 17.2 years); 8 patients with pheochromocytoma (5 M, 3 W; mean age 36.2 +/- 17.1 years); 15 patients with essential hypertension (9 M, 6 W; mean age 48.5 +/- 10 years). We also enrolled a normal control group (8 M, 12 W; mean age 34.2 +/- 11 years). The mean plasma ET-1 concentrations in patients with pheochromocytoma were significantly higher (23.9 +/- 5.2 pg/ml) than those in normal subjects (7.3 +/- 1.9 pg/ml), in patients with primary aldosteronism (12.1 +/- 3.8 pg/ml) and in patients with essential hypertension (9.2 +/- 3 pg/ml); p < 0.001, respectively. The present investigation demonstrates that in human adrenal hypertension patients with pheochromocytoma have increased circulating ET-1 levels respect to patients with aldosterone-producing adenoma.

Topics: Adenoma; Adrenal Gland Neoplasms; Adult; Biomarkers; Endothelin-1; Female; Humans; Hyperaldosteronism; Hypertension; Male; Middle Aged; Pheochromocytoma