{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T21:57:47Z","timestamp":1772661467555,"version":"3.50.1"},"reference-count":28,"publisher":"The Endocrine Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8,1]]},"abstract":"<jats:sec><jats:title>Context:<\/jats:title><jats:p>Aldosterone (ALD) secretion is regulated mainly by angiotensin II, K+, and adrenocorticotropic hormone (ACTH). Mineralocorticoid receptor antagonists (MRAs) have effectively been used for the treatment of patients with hypertension who do not have primary aldosteronism (PA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective:<\/jats:title><jats:p>We tested whether chronic stress\u2013related ACTH-mediated ALD hypersecretion and\/or zona glomerulosa hypersensitivity could be implicated in the pathogenesis of essential hypertension (ESHT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods:<\/jats:title><jats:p>One hundred thirteen hypertensives without PA and 61 normotensive controls underwent an ultralow-dose (0.03-\u03bcg) ACTH stimulation and a treadmill test. Patients with ALD hyper-response according to the cutoffs obtained from controls received treatment with MRAs and underwent genomic DNA testing for the presence of the CYP11B1\/CYP11B2 chimeric gene and KCNJ5 gene mutations. A control group of 22 patients with simple ESHT received treatment with MRAs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Based on the cutoffs of ALD and aldosterone-to-renin ratio (ARR) post-ACTH stimulation obtained from controls, 30 patients (27%) exhibited an ALD but not cortisol (F) hyper-response (HYPER group). This group had no difference in basal ACTH\/renin (REN) concentrations compared with controls and the 83 patients with hypertension (73%) without an ALD hyper-response to ACTH stimulation. Patients in the HYPER group demonstrated significantly higher ALD concentrations, ARR, and ALD\/ACTH ratio (AAR) in the treadmill test. Treatment with MRAs alone produced normalization of blood pressure in these patients whereas patients with hypertension with neither PA nor ALD hyper-response to ACTH stimulation who served as a control group failed to lower blood pressure. Also, two novel germline heterozygous KCNJ5 mutations were detected in the HYPER group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>A number of patients with hypertension without PA show ACTH-dependent ALD hyper-secretion and benefit from treatment with MRAs. This could be related to chronic stress via ACTH hyper secretion and\/or gene-mutations increasing the zona glomerulosa responsiveness to excitatory stimuli.<\/jats:p><\/jats:sec>","DOI":"10.1210\/jc.2015-1268","type":"journal-article","created":{"date-parts":[[2015,5,14]],"date-time":"2015-05-14T17:00:48Z","timestamp":1431622848000},"page":"2857-2864","source":"Crossref","is-referenced-by-count":97,"title":["Stress-induced Aldosterone Hyper-Secretion in a Substantial Subset of Patients With Essential Hypertension"],"prefix":"10.1210","volume":"100","author":[{"given":"Athina","family":"Markou","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Diabetes Center (A.M., I.I.A., C.M. T.P., A.G., L.P., S.F., D.R., G.P.P.), G. Gennimatas General Hospital, Athens 11527, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amalia","family":"Sertedaki","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics (A.S., E.C., G.P.C.), University of Athens Medical School, Aghia Sophia Children's Hospital, Athens 11527, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory","family":"Kaltsas","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology (G.K.), University of Athens Medical School, Laikon Hospital, Athens 11527, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioannis I.","family":"Androulakis","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes Center (A.M., I.I.A., C.M. T.P., A.G., L.P., S.F., D.R., G.P.P.), G. 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