Cause Of Secondary Hypertension Research Articles

#357 Sex differences in the aldosterone-renin system must be taken into account during screening for primary aldosteronism

Abstract Background and Aims Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Patients with PA are at higher risk for cardiovascular and renal complications than those with essential hypertension. Screening for PA is rarely considered in the assessment of a hypertensive patient, in part because of difficulties in the diagnostic process. Nevertheless, identification of PA is crucial to guide patients towards optimal management, either by mineralocorticoid receptor blockade or by unilateral adrenalectomy, with the latter offering potential cure for patients with aldosterone-producing adenomas (APAs). Numerous studies show inadequate diagnostic accuracy of the aldosterone:renin ratio (ARR) for screening for PA, particularly in females, who have higher ARR variability and lower renin compared to males. Women have a higher risk of false-positive screening results leading to unnecessary confirmatory tests. Use of oral contraception (OC) or hormone replacement therapy (HRT) may also confound the ARR. The aim of this study was to develop improved screening tools for PA, including adjustments for sex-specific differences. Method PROSALDO is a multicenter prospective cohort study designed to test new diagnostic procedures for patients with suspected PA. Medication that interfere with the renin-angiotensin-aldosterone system are withdrawn before laboratory measurements. For screening, the routine ARR is calculated along with additional probability scores based on a peripheral venous steroid hormone profile (PVSP). The latter allows for identification of potentially false-negative ARR results. After a positive screening result of the ARR and/or a high probability score based on the PVSP, PA is confirmed or excluded with a saline infusion test (SIT). PA confirmation is followed by adrenal venous sampling (AVS) to identify patients with unilateral PA. We compared aldosterone, renin and ARR levels between females and males with and without PA. Renin- and sex dependent formulas for aldosterone screening cut-offs were derived from the study population. Logistic regression and the corresponding receiver operating characteristic (ROC) curves were used to determine and compare diagnostic accuracies. Results PA was confirmed in 159 (24.5%) of 649 (328 (50.5%) females and 321 (49.5%) males). Lateralization was shown in 58 out of 117 patients who underwent AVS. In hypertensive patients without PA, ARR was higher in females vs. males (26.4 vs. 11.7 pmol/mU, P < 0.0001), mainly due to a lower renin (9.2 vs. 16.2 mU/L, P < 0.0001). Furthermore, ARRs in patients with vs. without PA showed more overlap in females compared to males. Areas under ROC curves (AUROCs) for the ARR were 0.857 (CI 95%: 0.797-0.902) vs. 0.912 (CI 95%: 0.876-0.938) for females and males respectively. Using liquid chromatography mass spectrometry measurements (LC-MS/MS) of aldosterone, an ARR cut-off of 21.75 pmol/L yielded a sensitivity of 93% with only 45% specificity in females, while for males, a specificity of 66% was obtained for a sensitivity of 97.7%. This meant for females having a higher risk of false-positive screening results (OR 2.36 (CI 95%: 1.65-3.41)), even after excluding patients on OC or HRT (OR 2.17 (CI 95%: 1.5-3.17)). We derived a renin- and sex-dependent formula for the calculation of aldosterone cut-offs, which improved diagnostic accuracy for both males and females (ΔAUROC = 0.05 and 0.045, P < 0.0001 and 0.02 respectively): for a diagnostic sensitivity of 94-95%, specificity was improved to 61% in females and 82% in males. Conclusion Lower renin in females without PA leads to higher ARRs and thus a higher risk of false-positive screening results. Higher overlap of the ARR between females with and without PA compared to their male counterparts weakens utility of the ARR for discrimination of patients with and without PA. Sex- and renin-specific aldosterone cut-offs for screening for PA offer improved diagnostic accuracy. Diagnostic accuracy remains however superior in males, which highlights the need for further optimization of diagnostic procedures specifically in women.

A Rare Case of Apparent Mineralocorticoid Excess Presenting as Endocrine Hypertension

A 3-year-old boy presented with polyuria and polydipsia for 18 months, along with growth failure. He was born prematurely, at 34 weeks of gestation, with a low birth weight. On examination, the child was severely underweight and hypertensive. Clinical history and evaluation could not identify any secondary causes of hypertension. There was no significant family history. An endocrine workup was planned, considering hypokalemia and metabolic alkalosis. This demonstrated hyporeninemic hypoaldosteronism and raised the possibility of apparent mineralocorticoid excess (AME) and Liddle syndrome. Clinical exome sequence analysis of HSD11B2 revealed a homozygous mutation in exon 5 (911A>G; p.His304Arg), which resulted in a missense mutation that confirmed the diagnosis of AME. A novel homozygous variant was found in the HSD11B2 gene in a subject with early onset hypertension associated with hypokalemic metabolic alkalosis, establishing the diagnosis of AME.

Diagnostic challenges in patients with reninomas and extrarenal renin-producing tumours.

Renin-secreting tumours are rare causes of secondary hypertension and hypokalaemia. They are usually surgically curable, hence proper diagnostic work-up and tumour localisation is essential. In this paper, we present three Swedish patients recently diagnosed with renin secreting tumours, two with reninomas and one with an extrarenal renin-producing tumour, to illustrate diagnostic challenges. We also discuss the biochemical work-up, the pros and cons of different imaging techniques (computer tomography [CT], magnetic resonance imaging and [18F]fluorodeoxyglucose-positron emission tomography-CT), as well as how renal vein sampling (RVC) may contribute to localisation of the tumour.

Emerging approaches in secondary hypertension due to renal artery stenosis: evaluation and treatment - systematic review

Hypertension, a global health concern, affects a staggering 1.28 billion people worldwide, as stated by the World Health Organization (WHO) however renal artery stenosis (RAS), a common cause of secondary hypertension, is characterized by the narrowing of renal arteries, leading to physiological changes such as arterial stiffening and elevated blood pressure. The major causes of RAS include atherosclerosis and fibromuscular dysplasia. Diagnosis involves clinical suspicion and imaging studies such as Doppler ultrasonography and angiography. Treatment strategies encompass lifestyle modifications, pharmacotherapy, interventional procedures like angioplasty with stenting, and emerging options such as renal denervation and gene therapy. Our aim is to provide a comprehensive examination of the pathophysiology, prevalence, risk factors, causes, diagnosis, and treatment modalities through a systematic search gathering qualitative and quantitative data. We address the challenges in diagnosis and treatment, emphasizing the need for tailored approaches considering patient-specific factors. We will review emerging approaches in evaluating and treating secondary hypertension due to RAS.

Primary aldosteronism and cardiovascular risk. Review

Primary aldosteronism (PA), a significant and curable cause of secondary hypertension, occurs in 5—10% of hypertensive patients, with prevalence dependent on the severity of hypertension. The main etiologies of PA include bilateral idiopathic hypertrophy (BIH) and aldosterone‑producing adenoma (APA), while less common causes include unilateral hyperplasia, familial hyperaldosteronism (FH) types I—IV, aldosterone‑producing carcinoma, and ectopic aldosterone synthesis. This condition, characterized by excessive secretion of aldosterone, leads to increased reabsorption of sodium and water along with potassium loss, culminating in the distinct clinical signs of elevated aldosterone, suppressed renin, and hypertension. It should be noted that hypokalemia is present in only 28% of patients with PA and is not the main indicator. The association of PA with an increased risk profile for cardiovascular disease, regardless of blood pressure level, is notable. Patients with PA show an increased rate of cardiovascular events compared to patients with essential hypertension, adjusted for age, sex, and blood pressure level. Despite its prevalence, PA often remains undiagnosed, highlighting the need for enhanced screening protocols. The diagnostic process for PA involves a three‑pronged assessment: the aldosterone/renin ratio (ARR) as the initial screening tool, followed by confirmatory and subtype tests. A positive ARR requires confirmatory testing to rule out false positives. Examination to detect PA should be carried out in patients with arterial hypertension: moderate (> 160—179/100—109 mm Hg) or severe (> 180/110 mm Hg); resistant to treatment; with idiopathic or diuretic‑induced hypokalemia; with an accidentally diagnosed tumor of the adrenal glands; if first‑generation relatives are diagnosed with PA, or family history indicates early onset of arterial hypertension, or cerebrovascular disorders at a young age (< 40 years); with accompanying obstructive sleep apnea.

Practical consensus for the treatment and follow-up of primary aldosteronism: a multidisciplinary consensus document.

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension and is associated with a higher cardiometabolic risk than essential hypertension. The aim of this consensus is to provide practical clinical recommendations for its surgical and medical treatment, pathology study and biochemical and clinical follow-up, as well as for the approach in special situations like advanced age, pregnancy and chronic kidney disease, from a multidisciplinary perspective, in a nominal group consensus approach of experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology and Spanish Association of Surgeons (AEC).

Laboratory Testing for Endocrine Hypertension: Current and Future Perspectives.

Secondary hypertension (SH) is a form of high blood pressure caused by an identifiable underlying condition. Although, it accounts for a small fraction of the overall hypertensive population, detection and management of SH is of utmost importance, because SH phenotypes carry a high cardiovascular risk and can possibly be cured by timely treatment. This review focuses on the endocrine causes of SH, such as primary aldosteronism, Cushing syndrome, thyroid disease, pheochromocytoma and paraganglioma, acromegaly, and rare monogenic forms. It discusses current biomarkers, analytical methods, and diagnostic strategies, highlighting advantages and limitations of each approach. It also explores the emerging -omics technologies that can provide a comprehensive and multidimensional assessment of SH and its underlying mechanisms. Endocrine SH is a heterogeneous and complex condition that requires proper screening and confirmatory tests to avoid diagnostic delays and improve patient outcomes. Careful biomarker interpretation is essential due to potential interferences, variability, and method-dependent differences. Liquid chromatography-tandem mass spectrometry is a superior method for measuring low-concentration hormones and metabolites involved in SH, but it requires expertise. Omics approaches have great potential to identify novel biomarkers, pathways, and targets for SH diagnosis and treatment, especially considering its multifactorial nature.

Prevalence of primary aldosteronism in acute stroke or transient ischemic attack: a systematic review and meta-analysis.

Primary aldosteronism (PA) is the most common endocrine cause of secondary hypertension with a prevalence of 14% in patients with newly diagnosed hypertension. Patients with PA experience a higher rate of cardiovascular events including stroke when compared to those with blood pressure matched essential hypertension. This systematic review and meta-analysis summarize current evidence on the prevalence of PA in patients with acute stroke or transient ischemic attack (TIA). Two reviewers independently reviewed the literature for observational studies on the prevalence of PA in patients with acute stroke or TIA. MEDLINE and Embase were searched for studies up to December 13, 2023. Three single center studies conducted in Japan, Singapore and China were found to meet the inclusion criteria. The reported prevalence of PA in two cohort studies of adults with stroke or TIA were 3.1% and 4.0% and a third cross-sectional study in adults under 45 years old revealed a prevalence rate of 12.9%. Following a meta-analysis, the pooled prevalence of PA in adults with stroke or TIA is 5.8% [95% CI 1.6%-12.3%]. A considerable proportion of patients with stroke or TIA may have PA as the underlying cause of their hypertension. Given the increased risk of stroke associated with PA, clinicians should consider screening for PA in hypertensive patients with stroke or TIA. Further research is needed to evaluate the effect of timing and interfering medications on test results, which will inform an evidence-based approach to testing for PA following TIA or stroke. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022328644.

Screening and diagnosis of primary aldosteronism. Consensus document of all the Spanish Societies involved in the management of primary aldosteronism.

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension (HT), and is associated with a higher cardiometabolic risk than essential HT. However, PA remains underdiagnosed, probably due to several difficulties clinicians usually find in performing its diagnosis and subtype classification. The aim of this consensus is to provide practical recommendations focused on the prevalence and the diagnosis of PA and the clinical implications of aldosterone excess, from a multidisciplinary perspective, in a nominal group consensus approach by experts from the Spanish Society of Endocrinology and Nutrition (SEEN), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN), Spanish Society of Internal Medicine (SEMI), Spanish Radiology Society (SERAM), Spanish Society of Vascular and Interventional Radiology (SERVEI), Spanish Society of Laboratory Medicine (SEQC(ML)), Spanish Society of Anatomic-Pathology, Spanish Association of Surgeons (AEC).

Clear cell renal carcinoma - an unusual cause of secondary hyper-tension in a young patient: a case report

Clear cell renal carcinoma - an unusual cause of secondary hyper-tension in a young patient: a case report

What We Know about and What Is New in Primary Aldosteronism.

Primary aldosteronism (PA), a significant and curable cause of secondary hypertension, is seen in 5-10% of hypertensive patients, with its prevalence contingent upon the severity of the hypertension. The principal aetiologies of PA include bilateral idiopathic hypertrophy (BIH) and aldosterone-producing adenomas (APAs), while the less frequent causes include unilateral hyperplasia, familial hyperaldosteronism (FH) types I-IV, aldosterone-producing carcinoma, and ectopic aldosterone synthesis. This condition, characterised by excessive aldosterone secretion, leads to augmented sodium and water reabsorption alongside potassium loss, culminating in distinct clinical hallmarks: elevated aldosterone levels, suppressed renin levels, and hypertension. Notably, hypokalaemia is present in only 28% of patients with PA and is not a primary indicator. The association of PA with an escalated cardiovascular risk profile, independent of blood pressure levels, is notable. Patients with PA exhibit a heightened incidence of cardiovascular events compared to counterparts with essential hypertension, matched for age, sex, and blood pressure levels. Despite its prevalence, PA remains frequently undiagnosed, underscoring the imperative for enhanced screening protocols. The diagnostic process for PA entails a tripartite assessment: the aldosterone/renin ratio (ARR) as the initial screening tool, followed by confirmatory and subtyping tests. A positive ARR necessitates confirmatory testing to rule out false positives. Subtyping, achieved through computed tomography and adrenal vein sampling, aims to distinguish between unilateral and bilateral PA forms, guiding targeted therapeutic strategies. New radionuclide imaging may facilitate and accelerate such subtyping and localisation. For unilateral adrenal adenoma or hyperplasia, surgical intervention is optimal, whereas bilateral idiopathic hyperplasia warrants treatment with mineralocorticoid antagonists (MRAs). This review amalgamates established and emerging insights into the management of primary aldosteronism.

Evaluation of a Best-Practice Advisory for Primary Aldosteronism Screening

Primary aldosteronism (PA) is a common cause of secondary hypertension and an independent risk factor for cardiovascular morbidity and mortality. Fewer than 2% to 4% of patients at risk are evaluated for PA. To develop and evaluate an electronic health record best-practice advisory (BPA) that assists with PA screening. This prospective quality improvement study was conducted at academic center outpatient clinics. Data analysis was performed between February and June 2023 and included adults with hypertension and at least 1 of the following: 4 or more current antihypertensive medications; hypokalemia; age younger than 35 years; or adrenal nodule(s). Patients previously tested for PA were excluded. A noninterruptive BPA was developed to trigger for PA screening candidates seen in outpatient setting by clinicians who treat hypertension. The BPA included an order set for PA screening and a link to results interpretation guidance. (1) The number of PA screening candidates identified by the BPA between October 1, 2021, and December 31, 2022; (2) the rates of PA screening; and (3) the BPA use patterns, stratified by physician specialty were assessed. Over 15 months, the BPA identified 14 603 unique candidates (mean [SD] age, 65.5 [16.9] years; 7300 women [49.9%]; 371 [2.5%] Asian, 2383 [16.3%] Black, and 11 225 [76.9%] White individuals) for PA screening, including 7028 (48.1%) with treatment-resistant hypertension, 6351 (43.5%) with hypokalemia, 1537 (10.5%) younger than 35 years, and 445 (3.1%) with adrenal nodule(s). In total, 2040 patients (14.0%) received orders for PA screening. Of these, 1439 patients (70.5%) completed the recommended screening within the system, and 250 (17.4%) had positive screening results. Most screening orders were placed by internists (40.0%) and family medicine physicians (28.1%). Family practitioners (80.3%) and internists (68.9%) placed most orders via the embedded order set, while specialists placed most orders (83.0%-95.4%) outside the BPA. Patients who received screening were younger and included more women and Black patients than those not screened. The likelihood of screening was higher among patients with obesity and dyslipidemia and lower in those with chronic kidney disease and established cardiovascular complications. The study results suggest that noninterruptive BPAs are potentially promising PA screening-assistance tools, particularly among primary care physicians. Combined with artificial intelligence algorithms that optimize the detection yield, refined BPAs may contribute to personalized hypertension care.

Hypertension in the emergency department: A missed opportunity to screen for primary aldosteronism?

Primary aldosteronism (PA) is a common but underdiagnosed secondary cause of hypertension. Emergency departments (EDs) often assess patients with severe hypertension or its sequelae, some of whom have underlying PA. We aimed to determine the proportion of patients presenting to the ED with hypertension who meet the Endocrine Society criteria for PA testing and the proportion who were screened. We performed a structured retrospective chart review of adults who presented to three EDs in an Australian tertiary health network between August 2019 and February 2020, with a coded presenting complaint of hypertension. Clinical parameters to determine whether the patients met the criteria for PA testing were extracted from electronic medical records. Of the 418 patients who presented to the EDs with documented elevated blood pressure (BP), 181 patients (43.3%) fulfilled PA screening criteria and nine patients (2.2%) underwent PA testing. Individuals who fulfilled screening criteria were older; had higher prevalence of Type 2 diabetes, coronary artery disease, and congestive heart failure; took more antihypertensive medications; and had lower estimated glomerular filtration rate. Individuals who were tested for PA were younger and had higher BP on presentation. Screening for PA was more frequent in patients who were referred to medical teams. As far as we are aware, our study is the first to evaluate PA testing in hypertensive patients who present to ED. More than 40% of adults presenting to the EDs with hypertension met the current criteria for testing for PA but only few were tested. These results emphasize that increased awareness of PA in the ED is needed to encourage opportunistic testing, referral, and treatment, especially in patients who present with hypertensive emergencies. Prospective studies are required to determine the feasibility and effectiveness of this.

Update on Primary Aldosteronism: Time to Screen All Hypertensives.

Primary aldosteronism (PA), characterized by autonomous renin-independent aldosterone production, is the most common endocrine cause of hypertension.1 PA was initially considered a rare cause of secondary hypertension, as experts described 0.451% prevalence in mild to moderate hypertension when hypokalemia was an essential reason for screening.1 However, recent data suggests that PA may be present even in patients with normokalemia, and 515% of patients in the hypertensive cohort have underlying overt PA.2.

Prevalence of Primary Aldosteronism and Complications in Type 2 Diabetes Mellitus Patients with Resistant Hypertension: A Prospective Observational Single Centre Study Protocol

Primary hyperaldosteronism (PA) has been thought to be an uncommon cause of hypertension, with an estimated prevalence of 2% among the general hypertensive population but is much higher, especially in resistant hypertension (RH) patients. Recent studies, however, have suggested that the prevalence of PA may be as high as 30% in RH populations. PA is associated with higher morbidity rates than matched essential hypertension patients. RH is more common in type 2 diabetes mellitus (T2DM). PA is generally remediable by treatment with an aldosterone antagonist or, in the case of adrenal adenoma, by adrenalectomy, knowing the true prevalence of PA is important for early diagnosis and treatment. Aim: This study aims to evaluate the prevalence of PA and cardiovascular (CVD) and renal complications in T2DM mellitus patients with resistant hypertension . Method: Prospective observational single centre study, in outpatient (OPD) settings in a tertiary care hospital. The primary outcome of the study is to estimate the prevalence of primary aldosteronism in T2DM patients with resistant hypertension. The secondary outcome is to evaluate the difference in prevalence of complications / comorbidities like CVD, left ventricle hypertrophy(LVH) , atrial fibrillation (AF), chronic kidney disease (CKD) in T2DM patients with and without PA hyperaldosteronism . T2DM patients aged more than 18 years with RH will be included in the study. Patients with type 1 diabetes mellitus or secondary causes of diabetes mellitus, acute diabetic complications, severe underlying systemic diseases, chronic kidney disease stage ≥4 , known secondary causes of hypertension, pregnancy and lactation and on medications like oral contraceptives, spironolactone, eplerenone, amiloride, triamterene will be excluded. Study subjects with plasma aldosterone to renin ratio of value ≥ 1.6 ng/dl/μIU/ml and plasma aldosterone concentration (PAC) of value ≥ 10 ng/dl with suppressed renin, will be considered to be positive on a screening test. Patients, those positive on a screening test will undergo seated saline suppression test (SST). Repeat plasma aldosterone concentration (PAC) with value ≥ 6 ng/dl will be confirmatory test for PA. Conclusion: RH specially in T2DM high-risk phenotype, which may be further aggravated by underlying PA . Thus we want to estimate the prevalence of PA in T2DM patients with RH. We also want to highlight any difference in prevalence of CV and renal complications due to in T2DM patients with and without PA, which may support early screening and diagnosis of PA and targeted treatment of PA to prevent its aggravating effects on chronic diabetes complications.

Adrenal venous sampling (AVS): Success of catheterization and concordance of imaging lateralization with AVS lateralization

Objective: Primary hyperaldosteronism (PA) is an important cause of secondary hypertension. One of the most crucial steps in the management of patients with PA is the determination of the laterality of aldosterone production (unilateral or bilateral disease). This study aimed to determine the success rate of adrenal venous sampling (AVS) and the concordance between imaging and AVS laterality. Material and Methods: The procedural, radiological, and laboratory data of the patients who underwent AVS were evaluated retrospectively. The Selectivity Index (SI) and Lateralization Index (LI) were used for catheterization success and laterality determination, respectively. The Contralateral Suppression Index (CSI) was used for laterality determination in cases of unilaterally failed AVS. Abdominal CT scans were evaluated for adrenal nodules and hyperplasia. Results: This study included 36 patients for catheterization success and 28 patients for laterality evaluation. The mean age was 56.08±9.01 years. The overall success rate was 88.9% (32 of 36 patients). The bilateral and unilateral successful catheterization rates were 52.8% and 36.2%, respectively. Unilateral disease was present in 15 (53.6%) patients based on AVS, right-sided in 9 (32.1%), and left-sided in 6 (21.4%) patients. Unilateral disease was present in 18 (64.3%) patients based on imaging, right-sided in 11 (39.3%), and left-sided in 7 (25%) patients. The proportion of agreement between imaging and AVS lateralization was 50% (14 of 28 patients). Conclusion: The overall success rate of AVS was high when unilateral success was included. In half of the patients with PA in this study, CT showed discordant disease laterality compared to AVS.

Imaging in the Causes of Secondary Hypertension: Unveiling the Hidden Culprits

AbstractSecondary hypertension refers to the cases of hypertension having a specific underlying etiology. Secondary hypertension can be further divided to endocrine or nonendocrine causes. Radiologists must accurately identify the secondary causes of hypertension, as many of them can be treated, and treatment can result in improved symptoms or resolution of hypertension. Secondary hypertension requires a thorough imaging investigation using ultrasound, Doppler ultrasound, computed tomography angiography, magnetic resonance imaging, scintigraphy, and other imaging techniques to identify the underlying cause for optimal management.

Unmasking the Silent Menace: A Case Report of Aldosterone-Secreting Adrenal Cortical Adenoma

Background: Adrenal cortical adenoma with aldosterone hypersecretion, the most prevalent cause of secondary hypertension, represents a significant subset of adrenal tumors with distinct clinical implications. Clinical Description: A 30-year-old female presented with generalized body pain for two years and multiple episodes of sudden onset progressive weakness of the upper and lower limbs. Management: The diagnosis was confirmed by serum aldosterone and plasma renin activity and a laparoscopic right adrenalectomy was performed. The histopathology of the removed specimen helped to rule out adrenal cortical carcinoma Conclusion: A prompt diagnosis and surgical management improves the quality of life for patients with such rare diseases.

Adrenal Vein Sampling in the Management of Primary Aldosteronism: The Added Value of Intraprocedural Cortisol Assessment.

Primary aldosteronism is the most common cause of secondary hypertension. Adrenal vein sampling is the gold standard for subtyping primary aldosteronism. However, this procedure is technically challenging and often has a low success rate. Our center is one of the very few performing this technique in our country with an increasing experience. The aim of this study was to evaluate the role of the cortisol intraprocedural assay in improving the performance of adrenal vein sampling. We enrolled all of the patients with primary aldosteronism that underwent adrenal vein sampling from February 2016 to April 2023. The cortisol intraprocedural assay was introduced in October 2021. We enrolled a total of 50 adrenal vein samplings performed on 43 patients with the diagnosis of primary aldosteronism. In this sample, 19 patients and 24 patients underwent adrenal vein sampling before and after intraprocedural cortisol measurement, respectively. The procedure was repeated in seven patients (one before and six after intraprocedural cortisol measurement), given the unsuccess of the first exam. Selectivity of the adrenal vein sampling was assumed if the serum cortisol concentration from the adrenal vein was at least five times higher than that of the inferior vena cava. Lateralization was assumed if the aldosterone to cortisol ratio of one adrenal vein was at least four times the aldosterone to cortisol ratio of the contralateral side. The mean age of the patients that underwent adrenal vein sampling (N = 43) was 55.2 ± 8.9 years, and 53.5% (n = 23) were female. The mean interval between the diagnosis of hypertension and the diagnosis of primary aldosteronism was 9.8 years (±9.9). At diagnosis, 62.8% of the patients (n = 27) had hypokalemia (mean value of 3 mmol/L (±0.34)), 88.4% (n = 38) had adrenal abnormalities on preprocedural CT scan, and 67.4% (n = 29) described as unilateral nodules. There were no statistically significant differences in the patients' baseline characteristics between the two groups (before and after intraprocedural cortisol measurement). Before intraprocedural cortisol measurement, adrenal vein sampling selectivity was achieved in 35% (n = 7) patients. Selectivity increased to 100% (30/30) after intraprocedural cortisol measurement (p < 0.001). With the exception of one patient who refused it, all patients with lateralized disease underwent unilateral adrenalectomy with normalization of the aldosterone to renin ratio postoperatively. The lack of effective alternatives in subtyping primary aldosteronism highlights the need to improve the success rate of adrenal vein sampling. In this study, intraprocedural cortisol measurement allowed a selectivity of 100%. Its addition to this procedure protocol should be considered, especially in centers with a low success rate.

Medical Measures in Hypertensives Considered Resistant.

Patients with resistant hypertension are the group of hypertensive patients with the highest cardiovascular risk. All rules and guidelines for treatment of hypertension should be followed strictly to obtain blood pressure (BP) control in resistant hypertension. The mainstay of treatment of hypertension, also for resistant hypertension, is pharmacological treatment, which should be tailored to each patient's specific phenotype. Therefore, it is pivotal to assess nonadherence to pharmacological treatment as this remains the most challenging problem to investigate and manage in the setting of resistant hypertension. Once adherence has been confirmed, patients must be thoroughly worked-up for secondary causes of hypertension. Until such possible specific causes have been clarified, the diagnosis is apparent treatment-resistant hypertension (TRH). Surprisingly few patients remain with true TRH when the various secondary causes and adherence problems have been detected and resolved. Refractory hypertension is a term used to characterize the treatment resistance in hypertensive patients using ≥5 antihypertensive drugs. All pressor mechanisms may then need blockage before their BPs are reasonably controlled. Patients with resistant hypertension need careful and sustained follow-up and review of their medications and dosages at each term since medication adherence is a very dynamic process.