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J Clin Endocrinol Metab. 2015 Aug;100(8):2857-64. doi: 10.1210/jc.2015-1268. Epub 2015 May 14.

Stress-induced Aldosterone Hyper-Secretion in a Substantial Subset of Patients With Essential Hypertension.

Author information

1
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; 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; Department of Pathophysiology (G.K.), University of Athens Medical School, Laikon Hospital, Athens 11527, Greece; and Department of Cardiology (A.Z., A.K.), G. Gennimatas General Hospital, Athens 11527, Greece.

Abstract

CONTEXT:

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).

OBJECTIVE:

We tested whether chronic stress-related ACTH-mediated ALD hypersecretion and/or zona glomerulosa hypersensitivity could be implicated in the pathogenesis of essential hypertension (ESHT).

PATIENTS AND METHODS:

One hundred thirteen hypertensives without PA and 61 normotensive controls underwent an ultralow-dose (0.03-μg) 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.

RESULTS:

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.

CONCLUSIONS:

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.

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PMID:
25974737
DOI:
10.1210/jc.2015-1268
[Indexed for MEDLINE]

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