Περίληψη:
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-mu g) 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.
Συγγραφείς:
Markou, Athina
Sertedaki, Amalia
Kaltsas, Gregory and
Androulakis, Ioannis I.
Marakaki, Chrisanthi
Pappa, Theodora and
Gouli, Aggeliki
Papanastasiou, Labrini
Fountoulakis, Stelios and
Zacharoulis, Achilles
Karavidas, Apostolos
Ragkou, Despoina and
Charmandari, Evangelia
Chrousos, George P.
Piaditis, George P.
