Incidence of Atrial Fibrillation and Mineralocorticoid Receptor Activity in Patients With Medically and Surgically Treated Primary Aldosteronism.

Importance: Primary aldosteronism (PA) is an ideal condition to evaluate the role of the mineralocorticoid receptor (MR) in the pathogenesis of atrial fibrillation (AF).

Objective: To investigate whether MR antagonist therapy or surgical adrenalectomy in PA influence the risk for incident AF.

Design: This cohort study included patients aged 18 years and older.

Renal Outcomes in Medically and Surgically Treated Primary Aldosteronism.

Lifelong therapy with mineralocorticoid receptor antagonists (MRAs) or surgical adrenalectomy are the recommended treatments for primary aldosteronism (PA). Whether these treatments mitigate the risk for kidney disease remains unknown. We performed a retrospective cohort study of patients with PA treated with MRAs (N=400) or surgical adrenalectomy (N=120) and age- and estimated glomerular filtration rate-matched patients with essential hypertension (N=15 474) to determine risk for chronic kidney disease and longitudinal estimated glomerular filtration rate decline.

The Lateralizing Asymmetry of Adrenal Adenomas.

Context: It is presumed that the incidence of adrenal adenomas is symmetric between the left and right adrenal gland; however, anecdotal observations suggest a potential lateralizing asymmetry.

Objective: To investigate the symmetry in detection of adrenal adenomas and relevance to patient care.

Design: Cross-sectional and longitudinal studies.

The Low-Renin Hypertension Phenotype: Genetics and the Role of the Mineralocorticoid Receptor.

A substantial proportion of patients with hypertension have a low or suppressed renin. This phenotype of low-renin hypertension (LRH) may be the manifestation of inherited genetic syndromes, acquired somatic mutations, or environmental exposures. Activation of the mineralocorticoid receptor is a common final mechanism for the development of LRH.

Cardiometabolic outcomes and mortality in medically treated primary aldosteronism: a retrospective cohort study.

Background: Mineralocorticoid receptor (MR) antagonists are the recommended medical therapy for primary aldosteronism. Whether this recommendation effectively reduces cardiometabolic risk is not well understood. We aimed to investigate the risk of incident cardiovascular events in patients with primary aldosteronism treated with MR antagonists compared with patients with essential hypertension.

Adrenocortical carcinoma and succinate dehydrogenase gene mutations: an observational case series.

Objective: Germline loss-of-function mutations in succinate dehydrogenase () genes results in rare tumor syndromes that include pheochromocytoma, paraganglioma, and others. Here we report a case series of patients with adrenocortical carcinoma (ACC) that harbor mutations.

Patients And Results: We report four unrelated patients with ACC and mutations.

Age-Related Autonomous Aldosteronism.

Background: Both aging and inappropriate secretion of aldosterone increase the risk for developing cardiovascular disease; however, the influence of aging on aldosterone secretion and physiology is not well understood.

Methods: The relationship between age and adrenal aldosterone synthase (CYP11B2) expression was evaluated in 127 normal adrenal glands from deceased kidney donors (age, 9 months to 68 years). Following immunohistochemistry, CYP11B2-expressing area and areas of abnormal foci of CYP11B2-expressing cells, called aldosterone-producing cell clusters, were analyzed.

Genetic and Histopathologic Intertumor Heterogeneity in Primary Aldosteronism.

Context: Whether primary aldosteronism (PA) is the consequence of a monoclonal or multiclonal process is unclear.

Case Description: A 48-year-old man with severe bilateral PA refractory to medical therapy underwent unilateral adrenalectomy of the dominant adrenal. Although computed tomography showed three left-sided cortical nodules, postsurgical histopathology and genetic analysis revealed five different adrenocortical adenomas.

Renin Phenotypes Characterize Vascular Disease, Autonomous Aldosteronism, and Mineralocorticoid Receptor Activity.

Context: Mild cases of autonomous aldosterone secretion may go unrecognized using current diagnostic criteria for primary aldosteronism (PA).

Objective: To investigate whether the inability to stimulate renin serves as a biomarker for unrecognized autonomous aldosterone secretion and mineralocorticoid receptor (MR) activation.

Participants: Six hundred sixty-three normotensive and mildly hypertensive participants, who were confirmed to not have PA using current guideline criteria and were on no antihypertensive medications.

Continuum of Renin-Independent Aldosteronism in Normotension.

Primary aldosteronism is a severe form of autonomous aldosteronism. Milder forms of autonomous and renin-independent aldosteronism may be common, even in normotension. We characterized aldosterone secretion in 210 normotensives who had suppressed plasma renin activity (<1.

Dietary Sodium Restriction Increases the Risk of Misinterpreting Mild Cases of Primary Aldosteronism.

Context: The aldosterone to renin ratio (ARR) is recommended to screen for primary aldosteronism (PA).

Objective: To evaluate whether dietary sodium restriction results in misinterpretation of PA screening.

Participants: Untreated hypertensives with ARR more than 20 on a high dietary sodium intake (HS) were also evaluated on a low dietary sodium intake (LS) (n = 241).

The renin-angiotensin-aldosterone system and calcium-regulatory hormones.

There is increasing evidence of a clinically relevant interplay between the renin-angiotensin-aldosterone system and calcium-regulatory systems. Classically, the former is considered a key regulator of sodium and volume homeostasis, while the latter is most often associated with skeletal health. However, emerging evidence suggests an overlap in regulatory control.

Pheochromocytoma and paraganglioma in cyanotic congenital heart disease.

Context: Aberrant cellular oxygen sensing is a leading theory for development of pheochromocytoma (PHEO) and paraganglioma (PGL).

Objective: The objective of the study was to test the hypothesis that chronic hypoxia in patients with cyanotic congenital heart disease (CCHD) increases the risk for PHEO-PGL.

Design/setting/participants: We investigated the association between CCHD and PHEO-PGL with two complementary studies: study 1) an international consortium was established to identify congenital heart disease (CHD) patients with a PHEO-PGL diagnosis confirmed by pathology or biochemistry and imaging; study 2) the 2000-2009 Nationwide Inpatient Survey, a nationally representative discharge database, was used to determine population-based cross-sectional PHEO-PGL frequency in hospitalized CCHD patients compared with noncyanotic CHD and those without CHD using multivariable logistic regression adjusted for age, sex, and genetic PHEO-PGL syndromes.

Aldosterone, parathyroid hormone, and the use of renin-angiotensin-aldosterone system inhibitors: the multi-ethnic study of atherosclerosis.

Context: Aldosterone and PTH are implicated in the pathogenesis of cardiovascular and skeletal diseases. An expanding body of evidence supports a bidirectional and positive physiologic relationship between aldosterone and PTH. Large population-based studies confirming this relationship, and whether it may be targeted as a potential method to mitigate the clinical consequences associated with excess aldosterone and PTH, are needed.

Interactions between adrenal-regulatory and calcium-regulatory hormones in human health.

Purpose Of Review: To summarize the evidence characterizing the interactions between adrenal-regulating and calcium-regulating hormones, and the relevance of these interactions to human cardiovascular and skeletal health.

Recent Findings: Human studies support the regulation of parathyroid hormone (PTH) by the renin-angiotensin-aldosterone system (RAAS): angiotensin II may stimulate PTH secretion via an acute and direct mechanism, whereas aldosterone may exert a chronic stimulation of PTH secretion. Studies in primary aldosteronism, congestive heart failure, and chronic kidney disease have identified associations between hyperaldosteronism, hyperparathyroidism, and bone loss, which appear to improve when inhibiting the RAAS.

Aldosterone dysregulation with aging predicts renal vascular function and cardiovascular risk.

Aging and abnormal aldosterone regulation are both associated with vascular disease. We hypothesized that aldosterone dysregulation influences the age-related risk of renal vascular and cardiovascular disease. We conducted an analysis of 562 subjects who underwent detailed investigations under conditions of liberal and restricted dietary sodium intake (1124 visits) in the General Clinical Research Center.

Human interventions to characterize novel relationships between the renin-angiotensin-aldosterone system and parathyroid hormone.

Observational studies in primary hyperaldosteronism suggest a positive relationship between aldosterone and parathyroid hormone (PTH); however, interventions to better characterize the physiological relationship between the renin-angiotensin-aldosterone system (RAAS) and PTH are needed. We evaluated the effect of individual RAAS components on PTH using 4 interventions in humans without primary hyperaldosteronism. PTH was measured before and after study (1) low-dose angiotensin II (Ang II) infusion (1 ng/kg per minute) and captopril administration (25 mg×1); study (2) high-dose Ang II infusion (3 ng/kg per minute); study (3) blinded crossover randomization to aldosterone infusion (0.