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.

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Endothelin has various paracrine and endocrine effects on the male reproductive system. Testosterone is probably responsible for the higher endothelin levels in males. In addition, there is much ambiguity about the relationship between gonadotrophic hormones and endothelin. In order to study in more detail the relationship of endothelin with the hypothalamo-pituitary-gonadal axis in the male, we investigated 18 male patients with various forms of hypogonadism (seven with hypergonadotrophic hypogonadism and 11 with hypogonadotrophic hypogonadism). Eight age-matched healthy males served as controls. The basal endothelin levels in patients with hypogonadism (0.95 +/- 0.53 fmol ml(-1)) were significantly higher than those of the controls (0.54 +/- 0.06 fmol ml(-1); P < 0.05). Males with hypergonadotrophic hypogonadism had significantly increased endothelin concentrations (1.05 +/- 0.57 fmol ml(-1); P < 0.05), whereas those with hypogonadotrophic hypogonadism (0.89 +/- 0.53 fmol ml(-1)) had nonsignificantly (P > 0.05) elevated levels. No significant correlation was found between plasma endothelin levels and gonadotrophin, prolactin and testosterone concentrations. The results of this study suggest that plasma endothelin levels are increased in males with hypogonadism.