The Cl/HCO exchanger pendrin is downregulated during oral co-administration of exogenous mineralocorticoid and KCl in patients with primary aldosteronism.

In primary aldosteronism (PA), the occurrence of K loss and hypertension suggest alterations in renal tubular transport, but the molecular basis of these alterations in humans is unclear. In this study, urinary extracellular vesicles (uEVs) isolated from patients undergoing fludrocortisone suppression testing (FST, as a means of confirming or excluding PA) were analyzed using mass spectrometry-based proteomics to determine the combined effects of an aldosterone analogue, NaCl and KCl supplementation on renal tubular protein abundance. Of quantified proteins, the Cl/HCO exchanger pendrin decreased by a median 37% [-15, 57] (P < 0.

Biochemical, Histopathological, and Genetic Characterization of Posture-Responsive and Unresponsive APAs.

Context And Objective: Posture-responsive and posture-unresponsive aldosterone-producing adenomas (APAs) account for approximately 40% and 60% of APAs, respectively. Somatic gene mutations have been recently reported to exist in approximately 90% of APAs. This study was designed to characterize the biochemical, histopathologic, and genetic properties of these 2 types of APA.

Evaluating the Diversity of Emergency Medicine Foundation (EMF) Grant Recipients in the Last Decade.

Introduction: To study diversity of researchers and barriers to success among Emergency Medicine Foundation (EMF) grant recipients in the last 10 years.

Methods: EMF grant awardees were approached to complete a brief survey, which included demographics, queries related to contributions to the literature, success in obtaining grants, and any perceived barriers they encountered.

Results: Of the 342 researchers contacted by email, a total of 147 completed the survey for a response rate of 43%.

Measurement of Equilibrium Angiotensin II in the Diagnosis of Primary Aldosteronism.

Background: Many medications (including most antihypertensives) and physiological factors affect the aldosterone/renin ratio (ARR) when screening for primary aldosteronism (PA). We sought to validate a novel equilibrium angiotensin II (eqAngII) assay and compare correlations between the aldosterone/angiotensin II ratio (AA2R) and the current ARR under conditions affecting the renin-angiotensin system.

Methods: Among 78 patients recruited, PA was excluded in 22 and confirmed in 56 by fludrocortisone suppression testing (FST).

Diagnosis of Primary Aldosteronism by Seated Saline Suppression Test-Variability Between Immunoassay and HPLC-MS/MS.

Background: In primary aldosteronism (PA), excessive, autonomous secretion of aldosterone is not suppressed by salt loading or fludrocortisone. For seated saline suppression testing (SSST), the recommended diagnostic cutoff 4-hour plasma aldosterone concentration (PAC) measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS is 162 pmol/L. Most diagnostic laboratories, however, use immunoassays to measure PAC.

Pathogenesis of Familial Hyperaldosteronism Type II: New Concepts Involving Anion Channels.

Purpose Of Review: The application of advanced genetic techniques has recently begun to unravel the genetic basis for familial primary aldosteronism type 2 (FH-II).

Recent Findings: Whole-exome sequencing in a large family with FH-II revealed a shared rare damaging heterozygous variant in CLCN2 (chr.3: g.

Comparison of Seated With Recumbent Saline Suppression Testing for the Diagnosis of Primary Aldosteronism.

Context: Failure of plasma aldosterone suppression during fludrocortisone suppression testing (FST) or saline suppression testing (SST) confirms primary aldosteronism (PA). Aldosterone is often higher upright than recumbent in PA; upright levels are used during FST. In a pilot study (24 patients with PA), seated saline suppression testing (SSST) was more sensitive than recumbent saline suppression testing (RSST).

Aldosterone LC-MS/MS Assay-Specific Threshold Values in Screening and Confirmatory Testing for Primary Aldosteronism.

Context: Current threshold values for primary aldosteronism (PA) diagnostic testing are based on measuring aldosterone (PAC) using immunoassays. Quantification of PAC by liquid chromatography-tandem mass spectrometry (LC-MS/MS) yields lower values.

Objective: To compare aldosterone measurement by radioimmunoassay (RIA) with LC-MS/MS and evaluate performances of proposed LC-MS/MS-specific cutoffs for PA screening and confirmatory testing.

Effect of Combined Hormonal Replacement Therapy on the Aldosterone/Renin Ratio in Postmenopausal Women.

Background: Plasma aldosterone/renin ratio (ARR) is the most popular screening test for primary aldosteronism (PA). Because both estrogen and progesterone (including in oral contraceptive agents) affect aldosterone and renin levels, we studied the effects of combined hormonal replacement therapy (HRT) on ARR; renin was measured as both direct renin concentration (DRC) and plasma renin activity (PRA).

Methods: Fifteen normotensive, healthy postmenopausal women underwent measurement (seated, midmorning) of plasma aldosterone, DRC, PRA, electrolytes, and creatinine and urinary aldosterone, cortisol, electrolytes, and creatinine at baseline and after 2 weeks and 6 weeks of treatment with combined HRT (conjugated estrogens 0.

Effect of Moxonidine on the Aldosterone/Renin Ratio in Healthy Male Volunteers.

Background: The most popular screening test for primary aldosteronism is the plasma aldosterone/renin ratio (ARR). Medications, dietary sodium, posture, and time of day all affect renin and aldosterone levels and can result in false-negative or false-positive ARRs if not controlled. Most antihypertensive medications affect the ARR and can interfere with interpretation of results.

Primary Aldosteronism: Changing Definitions and New Concepts of Physiology and Pathophysiology Both Inside and Outside the Kidney.

In the 60 years that have passed since the discovery of the mineralocorticoid hormone aldosterone, much has been learned about its synthesis (both adrenal and extra-adrenal), regulation (by renin-angiotensin II, potassium, adrenocorticotrophin, and other factors), and effects (on both epithelial and nonepithelial tissues). Once thought to be rare, primary aldosteronism (PA, in which aldosterone secretion by the adrenal is excessive and autonomous of its principal regulator, angiotensin II) is now known to be the most common specifically treatable and potentially curable form of hypertension, with most patients lacking the clinical feature of hypokalemia, the presence of which was previously considered to be necessary to warrant further efforts towards confirming a diagnosis of PA. This, and the appreciation that aldosterone excess leads to adverse cardiovascular, renal, central nervous, and psychological effects, that are at least partly independent of its effects on blood pressure, have had a profound influence on raising clinical and research interest in PA.

In Primary Aldosteronism, Mineralocorticoids Influence Exosomal Sodium-Chloride Cotransporter Abundance.

Distal tubular sodium retention is a potent driver of hypertension, and the thiazide-sensitive sodium-chloride cotransporter (NCC) has a key role in this process. In humans, factors regulating NCC are unclear, but in animal models, aldosterone is a potent regulator, possibly via effects on plasma potassium. We studied the effects of the mineralocorticoid fludrocortisone on the abundance of NCC and its phosphorylated form (pNCC) as well as WNK lysine deficient protein kinase 4 (WNK4) and STE20/SPS1-related, proline alanine-rich kinase (SPAK) in human urinary exosomes.

Does ACTH improve the diagnostic performance of adrenal vein sampling for subtyping primary aldosteronism?

Objective: Adrenal vein sampling (AVS) is used for determining treatment options for primary aldosteronism (PA), but is a difficult procedure. Adrenocorticotropic hormone (ACTH) infusion or bolus has been reported to improve AVS success rates by increasing cortisol secretion, but effects on lateralization are controversial. We therefore assessed the effects of ACTH in regard to AVS success and lateralization in our unit, after a change in protocol to ACTH-stimulated AVS.

Clinical Management and Outcomes of Adrenal Hemorrhage Following Adrenal Vein Sampling in Primary Aldosteronism.

Aldosterone-producing adenoma and bilateral adrenal hyperplasia account for >90% of all primary aldosteronism cases. Distinguishing between bilateral and unilateral disease is of fundamental importance because it allows targeted therapy. Adrenal vein sampling (AVS) is the only reliable means to preoperatively differentiate between unilateral and bilateral subtypes.

Novel Insertion Mutation in KCNJ5 Channel Produces Constitutive Aldosterone Release From H295R Cells.

Primary aldosteronism accounts for 5%-10% of hypertension and in a third of cases is caused by autonomous aldosterone production by adenomas (APA). Somatic mutations in the potassium channel encoded by KCNJ5 have been detected in surgically removed APAs. To better understand the role of these mutations, we resequenced the KCNJ5 channel in a large Australian primary aldosteronism cohort.

Urinary clonidine suppression testing for the diagnosis of pheochromocytoma.

Objective: The diagnosis of pheochromocytoma/paraganglioma (PPGL) involves detection of elevated levels of plasma and/or 24-h urine catecholamines and/or their metabolites, including metanephrines. Although these tests are reasonably sensitive, false-positive results are often encountered. Follow-up tests can provide additional information to correctly diagnose PPGL.

The utility of renal venous renin studies in selection of patients with renal artery stenosis for angioplasty: a retrospective study.

Objectives: Recent studies of renal artery stenosis (RAS) failed to demonstrate greater benefit from angioplasty in terms of blood pressure (BP) lowering than medical treatment. Not all RAS are haemodynamically significant and identification of patients likely to benefit from angioplasty remains essential.

Methods: We examined whether performing renal venous renin studies under stringent conditions might predict BP improvement.

Does concomitant autonomous adrenal cortisol overproduction have the potential to confound the interpretation of adrenal venous sampling in primary aldosteronism?

Objective: Demonstration of unilateral aldosterone production by adrenal venous sampling (AVS) is required to select appropriate candidates for adrenalectomy in patients with primary aldosteronism (PA). During AVS, aldosterone and cortisol levels are measured to assess successful cannulation and lateralization. In patients with aldosterone-producing adenoma (APA), concurrent autonomous cortisol secretion might confound AVS results.

Does contralateral suppression at adrenal venous sampling predict outcome following unilateral adrenalectomy for primary aldosteronism? A retrospective study.

Context: In primary aldosteronism (PA), adrenal vein sampling (AVS) distinguishes unilateral and bilateral disease by comparison of aldosterone/cortisol (A/F) ratios. There is controversy about the criteria for interpretation, however, and in particular it is not clear whether contralateral suppression (CS) (defined as A/F(adrenal) ≤ A/F(peripheral) on the unaffected side) is important. We therefore performed a retrospective study to determine whether CS in surgically treated unilateral PA was associated with blood pressure (BP) and biochemical outcomes.

Should aldosterone suppression tests be conducted during a particular phase of the menstrual cycle, and, if so, which phase? Results of a preliminary study.

Background: As renin and aldosterone levels vary during the menstrual cycle, and are critical criteria for interpretation of aldosterone suppression tests to confirm or exclude primary aldosteronism, outcome of testing may vary depending on the menstrual cycle phase. We assessed the effect of timing within the menstrual cycle on levels of renin, aldosterone and female sex steroids during fludrocortisone suppression testing (FST).

Methods: In 22 women undergoing FST who experienced regular menstrual cycles, renin (measured as both plasma renin activity and direct renin concentration), aldosterone (mass spectrometry) and cortisol, progesterone, oestradiol, LH and FSH (immunoassay) levels were compared, relative to phase of cycle.