Subtype Identification of Surgically Curable Primary Aldosteronism During Treatment With Mineralocorticoid Receptor Blockade.

BACKGROUND: Current guidelines and consensus documents recommend withdrawal of mineralocorticoid receptor antagonists (MRAs) before primary aldosteronism (PA) subtyping by adrenal vein sampling (AVS), but this practice can cause severe hypokalemia and uncontrolled high blood pressure. Our aim was to investigate if unilateral PA can be identified by AVS during MRA treatment. METHODS: We compared the rate of unilateral PA identification between patients with and without MRA treatment in large data sets of patients submitted to AVS while off renin-angiotensin system blockers and ß-blockers. In sensitivity analyses, the between-group differences of lateralization index values after propensity score matching and the rate of unilateral PA identification in subgroups with undetectable (≤2 mUI/L), suppressed (<8.2 mUI/L), and unsuppressed (≥8.2 mUI/L) direct renin concentration levels were also evaluated. RESULTS: Plasma aldosterone concentration, direct renin concentration, and blood pressure values were similar in non-MRA-treated (n=779) and MRA-treated (n=61) patients with PA, but the latter required more antihypertensive agents (P=0.001) and showed a higher rate of adrenal nodules (82% versus 67%; P=0.022) and adrenalectomy (72% versus 54%; P=0.01). However, they exhibited no significant differences in commonly used AVS indices and the area under the receiving operating characteristic curve of lateralization index, both under unstimulated conditions and postcosyntropin. Several sensitivity analyses confirmed these results in propensity score matching adjusted models and in patients with undetectable, or suppressed or unsuppressed renin levels. CONCLUSIONS: At doses that controlled blood pressure and potassium levels, MRAs did not preclude the identification of unilateral PA at AVS. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01234220.

Coronary sinus diameter to estimate congestion and predict survival.

Background: Congestion predicts a poor prognosis, but its assessment is challenging in clinical practice and requires a multiparametric approach. We investigated if the coronary sinus (CS) diameter can predict mortality in a human model of rapid fluid unloading. Methods: We measured by echocardiography the CS, and the inferior vena cava (IVC) for comparison, in 60 patients with end-stage chronic kidney disease (ESKD) immediately before and after hemodialysis (HD; age 76 [57-81] years, 40% female, left ventricular ejection fraction 57 [53-56]%). Patients were prospectively followed up for all-cause mortality. Results: HD-induced decongestion decreased the maximum diameters of both CS and IVC (p ≤ 0.001 for all). The maximum diameter of the CS (CSmax) was as accurate as the IVC maximum diameter and collapsibility for the identification of congestion, defined as pre-hemodialysis status (AUROC CSmax = 0.902 vs IVC = 0.895, p = n.s.). A CSmax diameter after hemodialysis > 9 mm predicted all-cause mortality at 12 months (Log-rank Chi square = 11.49, p < 0.001). Conclusions: A persistently dilated CS after hemodialysis is a marker of residual congestion and predicts death at one year in high-risk ESKD patients.

RAndomized Clinical Trial Of NAfamostat Mesylate, A Potent Transmembrane Protease Serine 2 (TMPRSS2) Inhibitor, in Patients with COVID-19 Pneumonia.

Even though SARS-CoV-2 was declared by WHO as constituting no longer a public health emergency, the development of effective treatments against SARS-CoV-2 infection remains a critical issue to prevent complications, particularly in fragile patients. The protease inhibitor nafamostat, currently used in Japan and Korea for pancreatitis, owing to its anticoagulant properties for disseminated intravascular coagulation (DIC), is appealing for the treatment of COVID-19 infection, because it potently inhibits the transmembrane protease serine 2 (TMPRSS2) that, after virus binding to ACE-2, allows virus entry into the cells and replication. Moreover, it could prevent the DIC and pulmonary embolism frequently associated with COVID-19 infection. The goal of the RAndomized Clinical Trial Of NAfamostat (RACONA) study, designed as a prospective randomized, double-blind placebo-controlled clinical trial, was to investigate the efficacy and safety of nafamostat mesylate (0.10 mg/kg/h iv for 7 days), on top of the optimal treatment, in COVID-19 hospitalized patients. We could screen 131 patients, but due to the predefined strict inclusion and exclusion criteria, only 15 could be randomized to group 1 (n = 7) or group 2 (n = 8). The results of an ad interim safety analysis showed similar overall trends for variables evaluating renal function, coagulation, and inflammation. No adverse events, including hyperkalemia, were found to be associated with nafamostat. Thus, the RACONA study showed a good safety profile of nafamostat, suggesting that it could be usefully used in COVID-19 hospitalized patients.

Pickering Syndrome: An Overlooked Renovascular Cause of Recurrent Heart Failure.

ABSTRACTRecurring and rapidly developing (flash) pulmonary edema is the hallmark of Pickering syndrome, affecting patients with hypertension and atherosclerotic renal artery stenosis (either bilateral or unilateral) in a solitary functioning kidney, and impaired renal function. We herein report on a series of consecutive patients with recurrent hospital admissions for pulmonary edema, impaired renal function (chronic kidney disease class 4-5), and atherosclerotic bilateral renal artery stenosis, in whom Pickering syndrome had been long neglected. We also describe a streamlined diagnostic strategy entailing little or no need for contrast medium, thus carrying no risks of further worsening of renal function. This allowed us to make the correct diagnosis and opened the way to revascularization by percutaneous transluminal renal angioplasty with stent, which provided swift recovery of kidney function with resolution of pulmonary congestion and long-term pulmonary edema- and dialysis-free survival in all cases. In summary, these findings support the following key messages: (1) considering the diagnosis of Pickering syndrome, followed by searching atherosclerotic renal artery stenosis, is an essential step toward a life-saving revascularization that avoids dialysis and an otherwise poor outcome; and (2) a simplified strategy entailing little or no need for contrast medium, carrying no associated risks of deteriorating renal function, permits the diagnosis of Pickering syndrome.

Aldosterone Biosynthesis Is Potently Stimulated by Perfluoroalkyl Acids: A Link between Common Environmental Pollutants and Arterial Hypertension.

The large environmental contamination of drinking water by perfluoroalkyl substances (PFAS) markedly increased the plasma levels of pentadecafluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in a Northern Italy population with a high prevalence of arterial hypertension and cardiovascular disease. As the link between PFAS and arterial hypertension is unknown, we investigated if they enhance the biosynthesis of the well-known pressor hormone aldosterone. We found that PFAS increased aldosterone synthase (CYP11B2) gene expression by three-fold and doubled aldosterone secretion and cell and mitochondria reactive oxygen species (ROS) production over controls (p < 0.01 for all) in human adrenocortical carcinoma cells HAC15. They also enhanced the effects of Ang II on CYP11B2 mRNA and aldosterone secretion (p < 0.01 for all). Moreover, when added 1 h before, the ROS scavenger tempol abolished the effect of PFAS on CYP11B2 gene expression. These results indicate that at concentrations mimicking those found in human plasma of exposed individuals, PFAS are potent disruptors of human adrenocortical cell function, and might act as causative factors of human arterial hypertension via increased aldosterone production.

Unilaterally Selective Adrenal Vein Sampling for Identification of Surgically Curable Primary Aldosteronism.

BACKGROUND: Adrenal venous sampling is recommended for the identification of unilateral surgically curable primary aldosteronism but is often clinically useless, owing to failed bilateral adrenal vein cannulation. OBJECTIVES: To investigate if only unilaterally selective adrenal vein sampling studies can allow the identification of the responsible adrenal. METHODS: Among 1625 patients consecutively submitted to adrenal vein sampling in tertiary referral centers, we selected those with selective adrenal vein sampling results in at least one side; we used surgically cured unilateral primary aldosteronism as gold reference. The accuracy of different values of the relative aldosterone secretion index (RASI), which estimates the amount of aldosterone produced in each adrenal gland corrected for catheterization selectivity, was examined. RESULTS: We found prominent differences in RASI values distribution between patients with and without unilateral primary aldosteronism. The diagnostic accuracy of RASI values estimated by the area under receiver operating characteristic curves was 0.714 and 0.855, respectively, in the responsible and the contralateral side; RASI values >2.55 and ≤0.96 on the former and the latter side furnished the highest accuracy for detection of surgically cured unilateral primary aldosteronism. Moreover, in the patients without unilateral primary aldosteronism, only 20% and 16% had RASI values ≤0.96 and >2.55. CONCLUSIONS: With the strength of a large real-life data set and use of the gold reference entailing an unambiguous diagnosis of unilateral primary aldosteronism, these results indicate the feasibility of identifying unilateral primary aldosteronism using unilaterally selective adrenal vein sampling results. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01234220.

Exclusion Tests in Unilateral Primary Aldosteronism (ExcluPA) Study.

CONTEXT: Determining the diagnostic accuracy of "exclusion" tests for primary aldosteronism (PA) compared to the aldosterone to renin ratio (ARR) is fundamental to avoid invasive subtyping in false-positive patients at screening. OBJECTIVE: To assess the accuracy of exclusion tests for PA using the diagnosis of unilateral PA as reference. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched for studies published from January 1, 1970, to December 31, 2021, meeting tight quality criteria. Data were extracted following the PRISMA methodology. We performed a two-stage meta-analysis that entailed an exploratory and a validation phase based on a "golden" or "gold" diagnostic standard, respectively. Pooled specificity, negative likelihood ratio, diagnostic odds ratio, and summary area under the ROC curve (sAUROC) were calculated to analyze the accuracy of exclusion tests. RESULTS: A meta-analysis of 31 datasets comprising a total of 4242 patients fulfilling the predefined inclusion criteria found that pooled accuracy estimates (sAUROC) did not differ between the ARR (0.95; 95% CI, 0.92-0.98), the captopril challenge test (CCT) (0.92; 95% CI, 0.88-0.97), and the saline infusion test (SIT) (0.96; 95% CI, 0.94-0.99). Solid information could not be obtained for the fludrocortisone suppression test and the furosemide upright test, which were assessed in only 1 study each. CONCLUSION: The apparently high diagnostic accuracy of the CCT and the SIT was due to the selection of patients with an elevated ARR and thus a high pretest probability of unilateral PA; however, neither test furnished a diagnostic gain over the ARR. Therefore, the systematic use of these exclusion tests in clinical practice is not justified by available evidence.

Management and Outcomes of Primary Aldosteronism in Pregnancy: A Systematic Review.

Primary aldosteronism (PA) in pregnancy (PAP) can be a serious condition and is challenging to diagnose. This study was conceived to help in the diagnosis of PAP and provide suggestions on management of PAP based on evidence retrieved using a Population, Intervention, Comparison, and Outcome search strategy. Based on the changes of aldosterone and renin occurring in normal pregnancies, we developed a nomogram that will allow to identify PAP cases. Moreover, we found that published PAP cases fell into 4 main groups differing for management and outcomes: (1) unilateral medically treated, (2) unilateral surgically treated, (3) bilateral medically treated and (4) familial forms. Results showed that complications involved 62.2% of pregnant women with nonfamilial PA and 18.5% of those with familial hyperaldosteronism type I. Adrenalectomy during pregnancy in women with PAP did not improve maternal and fetal outcomes, over medical treatment alone. Moreover, cure of maternal hypertension and mother and baby outcome were better when unilateral PA was discovered and surgically treated before or after pregnancy. Therefore, fertile women with arterial hypertension should be screened for PA before pregnancy and, if necessary, subtyped to identify unilateral forms of PA. This will allow to furnish adequate counseling, a chance for surgical cure and, therefore, for a pregnancy not complicated by aldosterone excess.

Peptidergic G Protein-Coupled Receptor Regulation of Adrenal Function: Bench to Bedside and Back.

An altered secretion of adrenocortical and adrenomedullary hormones plays a role in the clinical syndromes of primary aldosteronism (PA), Cushing, and pheochromocytoma. Moreover, an altered production of adrenocortical hormones and/or an abnormal release of factors by the adrenal medulla are involved in several other diseases, including high blood pressure, congestive heart failure, liver cirrhosis, nephrotic syndrome, primary reninism, renovascular hypertension, Addison disease, Bartter, Gitelman, and virilization syndromes. Understanding the regulation of adrenal function and the interactions between adrenal cortex and medulla is, therefore, the prerequisite for mechanistic understanding of these disorders. Accumulating evidence indicates that the modulation of adrenal hormone biosynthesis is a process far more complex than originally thought, as it involves several factors, each cooperating with the other. Moreover, the tight vascular and neural interconnections between the adrenal cortex and medulla underlie physiologically relevant autocrine/paracrine interactions involving several peptides. Besides playing a pathophysiological role in common adrenal diseases, these complex mechanisms could intervene also in rare diseases, such as pheochromocytoma concomitant with adrenal Cushing or with PA, and PA co-occurring with Cushing, through mechanisms that remain to be fully understood at the molecular levels. Heterodimerization of G protein-coupled receptors (GPCRs) induced by peptide signaling is a further emerging new modulatory mechanism capable of finely tuning adrenal hormones synthesis and release. In this review we will examine current knowledge on the role of peptides that act via GPCRs in the regulation of adrenal hormone secretion with a particular focus on autocrine-paracrine signals.

Clinical efficacy and safety of angiogenesis inhibitors: sex differences and current challenges.

Vasoactive molecules, such as vascular endothelial growth factor (VEGF) and endothelins, share cytokine-like activities and regulate endothelial cell (EC) growth, migration, and inflammation. Some endothelial mediators and their receptors are targets for currently approved angiogenesis inhibitors, drugs that are either monoclonal antibodies raised towards VEGF, or inhibitors of vascular receptor protein kinases and signalling pathways. Pharmacological interference with the protective functions of ECs results in a similar spectrum of adverse effects. Clinically, the most common side effects of VEGF signalling pathway inhibition include an increase in arterial pressure, left ventricular dysfunction facilitating the development of heart failure, thromboembolic events including pulmonary embolism and stroke, and myocardial infarction. Sex steroids, such as androgens, progestins, and oestrogens and their receptors (ERα, ERß, GPER; PR-A, PR-B; AR) have been identified as important modifiers of angiogenesis, and sex differences have been reported for anti-angiogenic drugs. This review article discusses the current challenges clinicians are facing with regard to angiogenesis inhibitor therapy, including the need to consider sex differences affecting clinical efficacy and safety. We also propose areas for future research taking into account the role of sex hormone receptors and sex chromosomes. Development of new sex-specific drugs with improved target- and cell-type selectivity likely will open the way to personalized medicine in men and women requiring anti-angiogenic therapy to reduce adverse effects and to improve therapeutic efficacy.

Feasibility of Imaging-Guided Adrenalectomy in Young Patients With Primary Aldosteronism.

Many of the patients with primary aldosteronism (PA) are denied curative adrenalectomy because of limited availability or failure of adrenal vein sampling. It has been suggested that adrenal vein sampling can be omitted in young patients with a unilateral adrenal nodule, who show a florid biochemical PA phenotype. As this suggestion was based on a very low quality of evidence, we tested the applicability and accuracy of imaging, performed by computed tomography and/or magnetic resonance, for identification of unilateral PA, as determined by biochemical and/or clinical cure after unilateral adrenalectomy. Among 1625 patients with PA submitted to adrenal vein sampling in a multicenter multiethnic international study, 473 were ≤45 years of age; 231 of them had exhaustive imaging and follow-up data. Fifty-three percentage had a unilateral adrenal nodule, 43% had no nodules, and 4% bilateral nodules. Fifty-six percentage (n=131) received adrenalectomy and 128 were unambiguously diagnosed as unilateral PA. A unilateral adrenal nodule on imaging and hypokalemia were the strongest predictors of unilateral PA at regression analysis. Accordingly, imaging allowed correct identification of the responsible adrenal in 95% of the adrenalectomized patients with a unilateral nodule. The rate raised to 100% in the patients with hypokalemia, who comprised 29% of the total, but fell to 88% in those without hypokalemia. Therefore, a unilateral nodule and hypokalemia could be used to identify unilateral PA in patients ≤45 years of age if adrenal vein sampling is not easily available. However, adrenal vein sampling remains indispensable in 71% of the young patients, who showed no nodules/bilateral nodules at imaging and/or no hypokalemia. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01234220.

Identification of Surgically Curable Primary Aldosteronism by Imaging in a Large, Multiethnic International Study.

CONTEXT: Adrenal gland imaging is recommended by the current guidelines for the workup of primary aldosteronism (PA). However, its diagnostic performance has not been established in large, multiethnic cohorts of patients who undergo adrenal vein sampling (AVS) and adrenalectomy. OBJECTIVE: This work aims to assess the diagnostic accuracy of cross-sectional adrenal imaging. METHODS: This international multicenter study took place in tertiary referral centers. A total of 1625 PA patients seeking surgical cure were enrolled in an international study involving 19 centers in North America, Europe, Asia, and Australia. Of these, 1311 (81%) had imaging data available and 369 (23%), who received a final diagnosis of surgically cured unilateral PA, were examined. Patients underwent AVS and imaging by computed tomography and/or magnetic resonance imaging. The accuracy of detection of unilateral PA at imaging was estimated by the area under the receiver operator characteristics curve using cure (biochemical and/or full clinical success) as the reference at follow-up after unilateral adrenalectomy. RESULTS: In the cohort of 1311 patients with imaging data available, 34% and 7% of cases showed no detectable or bilateral nodules, respectively. Imaging did not detect the culprit adrenal in 28% of the surgically cured unilateral PA patients. Moreover, the clinical outcome did not differ significantly between the imaging-positive and imaging-negative patients. CONCLUSION: Cross-sectional imaging did not identify a lateralized cause of disease in around 40% of PA patients and failed to identify the culprit adrenal in more than one-fourth of patients with unilateral PA.

A systematic review of pathophysiology and management of familial hyperaldosteronism type 1 in pregnancy.

PURPOSE: Familial hyperaldosteronism type 1 (FH-1) is a rare autosomal dominant form of primary aldosteronism, which features a marked phenotypic heterogeneity, ranging from mild to severe forms of arterial hypertension that can be complicated by stroke and cardiovascular events at a young age. As affected patients usually reach the fertile age, transmission of the disease to offspring is common. Notwithstanding this, reports of FH-1 in pregnancy are limited and there is a lack of treatment guidelines. METHODS AND RESULTS: We searched the PubMed and EuropePMC databases with a PICO strategy to retrieve available information on management of FH-1 patients during pregnancy. We could identify seven relevant articles, which are herein reviewed. CONCLUSION: Based on available information on pathophysiology and treatment of FH-1 in pregnancy, recommendations for the rational management of FH-1 in pregnancy are provided.

Aldosterone and cortisol synthesis regulation by angiotensin-(1-7) and angiotensin-converting enzyme 2 in the human adrenal cortex.

OBJECTIVE: The branch of the renin--angiotensin system constituting angiotensin-(1-7) [Ang-(1-7)], the Ang II type 2 receptor, the Mas receptors and the Ang-(1-7)-forming enzyme ACE-2, by counteracting the Ang II type 1 receptor (AT1R)-mediated effects, are held to be cardiovascular protective in several conditions. However, whether Ang-(1-7) and ACE-2 are detectable in human adrenocortical tissues and whether they affect aldosterone and cortisol biosynthesis was unknown. METHODS: We measured angiotensin peptides with liquid chromatography tandem-mass spectrometry and ACE-2 mRNA with digital droplet (dd)PCR in human aldosterone-producing adenoma (APA) and APA-adjacent tissue obtained from patients with primary aldosteronism. We also investigated the effects of Ang-(1-7) and the ACE-2 activator diminazene aceturate (DIZE) on aldosterone synthase (CYP11B2) and 11ß-hydroxylase (CYP11B1) gene expression, in the absence or presence of the AT1R antagonist irbesartan, or of the MasR antagonist A779. RESULTS: APA and APA-adjacent adrenocortical tissues express ACE-2 mRNA and contain detectable amounts of Ang II and Ang-(2-8), but not of Ang I, Ang-(1-5), Ang (3-8) and Ang-(1-7). Under unstimulated and Ang II- stimulated conditions Ang-(1-7) did not blunt CYP11B1 and CYP11B2 mRNA. At supraphysiological concentrations (10-4 mol/l), Ang-(1-7) stimulated both CYP11B1 and CYP11B2 mRNA via the AT1R. The ACE-2 activator DIZE increased by 1.5-fold ACE-2 mRNA but did not blunt Ang II- upregulated CYP11B1 and CYP11B2 expression. CONCLUSION: These results do not support the hypothesis that the ACE-2/Ang-(1-7)/MasR axis play a protective role by counteracting enhanced aldosterone secretion in humans.

Familial hyperaldosteronism type 1 and pregnancy: successful treatment with low dose dexamethasone.

PURPOSE: Familial hyperaldosteronism type 1 (FH-1) is an autosomal dominant form of primary aldosteronism (PA), featuring a marked phenotypic heterogeneity, ranging from mild forms of PA and arterial hypertension (HT) to severe forms complicated by stroke at a young age. Affected patients usually reach the fertile age; hence, transmission of the disease to offspring is common. Notwithstanding this, only anecdotal reports of FH-1 in pregnancy exist and recommendations for treatment remain vague. MATERIALS AND METHODS AND RESULTS: We herein report on a novel FH-1 pedigree featuring very severe HT, fatal aortic dissection, and high rate of early stroke, where a young FH-1 woman was successfully managed throughout pregnancy with low-dose dexamethasone. CONCLUSIONS: Based on this experience and on available information on pathophysiology of FH-1 in pregnancy, the pros and cons of dexamethasone administration in the treatment of FH-1 in pregnancy are also discussed.

High sodium intake, glomerular hyperfiltration, and protein catabolism in patients with essential hypertension.

AIMS: A blood pressure (BP)-independent metabolic shift towards a catabolic state upon high sodium (Na+) diet, ultimately favouring body fluid preservation, has recently been described in pre-clinical controlled settings. We sought to investigate the real-life impact of high Na+ intake on measures of renal Na+/water handling and metabolic signatures, as surrogates for cardiovascular risk, in hypertensive patients. METHODS AND RESULTS: We analysed clinical and biochemical data from 766 consecutive patients with essential hypertension, collected at the time of screening for secondary causes. The systematic screening protocol included 24 h urine (24 h-u-) collection on usual diet and avoidance of renin-angiotensin-aldosterone system-confounding medications. Urinary 24 h-Na+ excretion, used to define classes of Na+ intake (low ≤2.3 g/day; medium 2.3-5 g/day; high >5 g/day), was an independent predictor of glomerular filtration rate after correction for age, sex, BP, BMI, aldosterone, and potassium excretion [P = 0.001; low: 94.1 (69.9-118.8) vs. high: 127.5 (108.3-147.8) mL/min/1.73 m2]. Renal Na+ and water handling diverged, with higher fractional excretion of Na+ and lower fractional excretion of water in those with evidence of high Na+ intake [FENa: low 0.39% (0.30-0.47) vs. high 0.81% (0.73-0.98), P < 0.001; FEwater: low 1.13% (0.73-1.72) vs. high 0.89% (0.69-1.12), P = 0.015]. Despite higher FENa, these patients showed higher absolute 24 h Na+ reabsorption and higher associated tubular energy expenditure, estimated by tubular Na+/ATP stoichiometry, accordingly [Δhigh-low = 18 (12-24) kcal/day, P < 0.001]. At non-targeted liquid chromatography/mass spectrometry plasma metabolomics in an unselected subcohort (n = 67), metabolites which were more abundant in high versus low Na+ intake (P < 0.05) mostly entailed intermediates or end products of protein catabolism/urea cycle. CONCLUSION: When exposed to high Na+ intake, kidneys dissociate Na+ and water handling. In hypertensive patients, this comes at the cost of higher glomerular filtration rate, increased tubular energy expenditure, and protein catabolism from endogenous (muscle) or excess exogenous (dietary) sources. Glomerular hyperfiltration and the metabolic shift may have broad implications on global cardiovascular risk independent of BP.

The cardiovascular consequences of hyperaldosteronism.

Primary aldosteronism (PA), the most common form of secondary hypertension, has been considered for decades as a "benign" form of hypertension, but evidences progressively built up to show that patients with PA had an excess rate of cardiovascular damage as compared to blood pressure-matched essential hypertensive patients. This review provides an updated view of structural and electrical cardiac remodeling and of vascular changes in hyperaldosteronism, and how they can favor development of cardiovascular events. The link between hyperaldosteronism and resistant hypertension is also examined, and the impact of targeted treatment of hyperaldosteronism on cardiovascular changes is finally discussed.

Practice Recommendations for Diagnosis and Treatment of the Most Common Forms of Secondary Hypertension.

The vast majority of hypertensive patients are never sought for a cause of their high blood pressure, i.e. for a 'secondary' form of arterial hypertension. This under detection explains why only a tiny percentage of hypertensive patients are ultimately diagnosed with a secondary form of arterial hypertension. The prevalence of these forms is, therefore, markedly underestimated, although, they can involve as many as one-third of the cases among referred patients and up to half of those with difficult to treat hypertension. The early detection of a secondary form is crucial, because if diagnosed in a timely manner, these forms can be cured at long-term, and even when cure cannot be achieved, their diagnosis provides a better control of high blood pressure, and allows prevention of hypertension-mediated organ damage, and related cardiovascular complications. Enormous progress has been made in the understanding, diagnostic work-up, and management of secondary hypertension in the last decades. The aim of this minireview is, therefore, to provide updated concise information on the screening, diagnosis, and management of the most common forms, including primary aldosteronism, renovascular hypertension, pheochromocytoma and paraganglioma, Cushing's syndrome, and obstructive sleep apnea.