{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:12:13Z","timestamp":1791216733807,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2007,2,9]],"date-time":"2007-02-09T00:00:00Z","timestamp":1170979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2007,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Objective\u2002<\/jats:bold> Although much is known about the anti\u2010inflammatory effects of an acute corticosteroid therapy, little is known about the effects on chronic hypercortisolism on endothelial dysfunction and proinflammatory alterations in patients with Cushing's disease (CD).<\/jats:p><jats:p><jats:bold>Patients and methods\u2002<\/jats:bold> We studied 9 patients with CD, 10 patients with metabolic syndrome and 27 normal controls. The tests consisted of an intravenous bolus of 0\u00b71\u00a0U\/kg insulin combined with a euglycaemic clamp technique with an arterialized forearm and assessment of the training parameters deep\u2010venous balance of forearm glucose uptake (as an index of insulin sensitivity); NO<jats:sub>x<\/jats:sub> (nitric oxide end\u2010products), c\u2010GMP (second messenger of nitric oxide) and endothelin\u20101 release, as indices of endothelial function and proinflammatory systemic markers.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> Forearm glucose uptake incremental area was significantly lower in Cushing's disease and in the metabolic syndrome than in controls, suggesting a state of severe insulin resistance. Compared to controls and to the metabolic syndrome, basal and insulin\u2010stimulated NO<jats:sub>x<\/jats:sub> release incremental areas were significantly reduced in Cushing's disease, while forearm c\u2010GMP release was similarly decreased in CD and metabolic syndrome. By contrast, endothelin\u20101 incremental areas after insulin bolus were significantly higher in CD than in controls and the metabolic syndrome, in the presence of increased TNF\u2010alpha, IL\u20106 and CRP levels. Forearm glucose uptake incremental area significantly correlated with NO<jats:sub>x<\/jats:sub> incremental area, forearm c\u2010GMP release incremental area, TNF\u2010alpha levels and ET\u20101 incremental area.<\/jats:p><jats:p><jats:bold>Conclusions\u2002<\/jats:bold> In patients with CD, supraphysiological insulin levels are not able to overcome the insulin resistance due to chronic hypercortisolism. Furthermore, an increased proatherogenic risk profile is characterized by decreased nitric oxide synthesis and activity, enhanced endothelin\u20101 levels and increased proinflammatory markers.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2007.02774.x","type":"journal-article","created":{"date-parts":[[2007,2,10]],"date-time":"2007-02-10T11:37:56Z","timestamp":1171107476000},"page":"586-592","source":"Crossref","is-referenced-by-count":20,"title":["Increased insulin\u2010stimulated endothelin\u20101 release is a distinct vascular phenotype distinguishing Cushing's disease from metabolic 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