Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline.

Background: Primary aldosteronism (PA), a primary adrenal disorder leading to excessive aldosterone production by one or both adrenal glands, is a common cause of hypertension. It is associated with an increased risk of cardiovascular complications compared with primary hypertension. Despite effective methods for diagnosing and treating PA, it remains markedly underdiagnosed and undertreated.

Identification of hypertension subtypes using microRNA profiles and machine learning.

Objective: Hypertension is a major cardiovascular risk factor affecting about 1 in 3 adults. Although the majority of hypertension cases (∼90%) are classified as "primary hypertension" (PHT), endocrine hypertension (EHT) accounts for ∼10% of cases and is caused by underlying conditions such as primary aldosteronism (PA), Cushing's syndrome (CS), pheochromocytoma or paraganglioma (PPGL). EHT is often misdiagnosed as PHT leading to delays in treatment for the underlying condition, reduced quality of life and costly, often ineffective, antihypertensive treatment.

Prevalence and main characteristics of primary aldosteronism in bilateral macronodular adrenal disease: a systematic review of the literature.

Context: Bilateral macronodular adrenal disease (BMAD) typically presents with bilateral benign adrenocortical macronodules and variable cortisol excess. Anecdotal evidence suggests oversecretion of other adrenal steroids, including mineralocorticoids.

Hypothesis: We hypothesized that primary aldosteronism (PA) can occur in BMAD, resulting in a distinct, more severe phenotype compared to BMAD with isolated cortisol hypersecretion or unilateral PA (uPA).

Screening of primary aldosteronism and pheochromocytoma among patients with hypertension: an Italian nationwide survey.

Purpose: The delayed or missed diagnosis of secondary hypertension contributes to the poor blood pressure control worldwide. This study aimed to assess the diagnostic approach to primary aldosteronism (PA) and pheochromocytoma (PHEO) among Italian centers associated to European and Italian Societies of Hypertension.

Methods: Between July and December 2023, a 10-items questionnaire was administered to experts from 82 centers of 14 Italian regions and to cardiologists from the ARCA (Associazioni Regionali Cardiologi Ambulatoriali) Piemonte.

Outcomes after medical treatment for primary aldosteronism: an international consensus and analysis of treatment response in an international cohort.

Background: Primary aldosteronism can be treated medically but there is no standardised method to evaluate treatment outcomes. We aimed to develop criteria for assessing the outcomes of targeted medical treatment of primary aldosteronism, analyse outcomes across an international cohort, and identify factors associated with a complete treatment response.

Methods: An international panel of 31 primary aldosteronism experts used the Delphi method to reach consensus on the definition of complete, partial, or absent biochemical and clinical outcomes of medical treatment of primary aldosteronism.

Age- and sex-related variations in extracellular vesicle profiling for the assessment of cardiovascular risk: the EVaging index.

Extracellular vesicles (EVs) offer valuable diagnostic and prognostic insights for cardiovascular (CV) diseases, but the influence of age-related chronic inflammation ("inflammaging") and sex differences on EV profiles linked to CV risk remains unclear. This study aimed to use EV profiling to predict age and stratify patients by CV risk. We developed an EVaging index by analyzing surface antigen profiles of serum EVs from 625 participants, aged 20 to 94 years, across varying CV risk groups.

Management of Renovascular Hypertension and Renal Denervation in Patients with Hypertension: An Italian Nationwide Survey.

Introduction: Renovascular hypertension (RVH) remains underdiagnosed despite its significant cardiovascular and renal morbidity.

Aim: This survey investigated screening and management practices for RVH among hypertensive patients in Italian hypertension centres in a real-life setting. Secondary, we analysed the current spread of renal denervation (RDN) and the criteria used for its eligibility.

Safety and efficacy of once-daily dexfadrostat phosphate in patients with primary aldosteronism: a randomised, parallel group, multicentre, phase 2 trial.

Background: Primary aldosteronism (PA) is caused by autonomous aldosterone overproduction and characterised by uncontrolled hypertension. There are currently no treatments that target aldosterone synthesis. We evaluated the safety and efficacy of a novel aldosterone synthase inhibitor, dexfadrostat phosphate, in patients with PA.

Familial hyperaldosteronism: an European Reference Network on Rare Endocrine Conditions clinical practice guideline.

We describe herein the European Reference Network on Rare Endocrine Conditions clinical practice guideline on diagnosis and management of familial forms of hyperaldosteronism. The guideline panel consisted of 10 experts in primary aldosteronism, endocrine hypertension, paediatric endocrinology, and cardiology as well as a methodologist. A systematic literature search was conducted, and because of the rarity of the condition, most recommendations were based on expert opinion and small patient series.

Long-Term Follow-Up of Patients With Elevated Aldosterone-to-Renin Ratio but Negative Confirmatory Test: The Progression of Primary Aldosteronism Phenotypes.

Background: About 10% of patients with arterial hypertension have a positive screening test for primary aldosteronism (PA) and 50% to 70% of them have a negative confirmatory test: the appropriate follow-up of these patients is currently unknown. We investigated the incidence of PA in patients with previous negative confirmatory testing, after at least a 2-year follow-up.

Methods: One hundred eighty-four patients with a previously elevated aldosterone-to-renin ratio followed by a negative confirmatory test were recruited in 2 hypertension centers (Torino and Munich).

Proteomic analysis of urinary extracellular vesicles highlights specific signatures for patients with primary aldosteronism.

Background: Urinary extracellular vesicles (uEVs) can be released by different cell types facing the urogenital tract and are involved in cellular trafficking, differentiation and survival. UEVs can be easily detected in urine and provide pathophysiological information "" without the need of a biopsy. Based on these premises, we hypothesized that uEVs proteomic profile may serve as a valuable tool in the differential characterization between Essential Hypertension (EH) and primary aldosteronism (PA).

Prevalence of Cortisol Cosecretion in Patients With Primary Aldosteronism: Role of Metanephrine in Adrenal Vein Sampling.

Context: Adrenal venous sampling (AVS) is the gold standard procedure for subtype diagnosis in patients with primary aldosteronism (PA). Cortisol is usually adopted for the normalization of aldosterone levels in peripheral and adrenal samples. However, asymmetrical cortisol secretion can potentially affect the lateralization index, leading to subtype misdiagnosis.

CYP11B2 inhibitor dexfadrostat phosphate suppresses the aldosterone-to-renin ratio, an indicator of sodium retention, in healthy volunteers.

Aims: High aldosterone is a key driver of hypertension and long-term negative sequelae. We evaluated the safety and efficacy of dexfadrostat phosphate (DP13), a novel aldosterone synthase (CYP11B2) inhibitor, in healthy participants.

Methods: This randomized, double-blind, placebo-controlled study was conducted in two parts.

Prevalence of Functioning Adrenal Incidentalomas: A Systematic Review and Meta-analysis.

Context: Adrenal hyperfunction is associated with an increased risk of cardiometabolic complications in subjects with adrenal incidentaloma (AI). Reliable prevalence estimates of functioning AIs are important to direct resources allocations.

Objective: To assess the prevalence of autonomous/possible autonomous cortisol secretion (ACS), primary aldosteronism (PA), pheochromocytoma (PHEO), and Cushing syndrome (CS) in patients with AI.

TSPAN12 (Tetraspanin 12) Is a Novel Negative Regulator of Aldosterone Production in Adrenal Physiology and Aldosterone-Producing Adenomas.

Background: Aldosterone-producing adenomas (APAs) are a major cause of primary aldosteronism, a condition of low-renin hypertension, in which aldosterone overproduction is usually driven by a somatic activating mutation in an ion pump or channel. is differentially expressed in different subgroups of APAs suggesting a role in APA pathophysiology. Our objective was to determine the function of TSPAN12 (tetraspanin 12) in adrenal physiology and pathophysiology.

Cardiac Phenotypes in Secondary Hypertension: JACC State-of-the-Art Review.

Several forms of secondary hypertension carry a high risk of cardiac morbidity and mortality. Evaluation of cardiac phenotypes in secondary hypertension provides a unique opportunity to study underlying hormonal and biochemical mechanisms affecting the heart. We review the characteristics of cardiac dysfunction in different forms of secondary hypertension and clarify the mechanisms behind the higher prevalence of heart damage in these patients than in those with primary hypertension.

Machine learning for classification of hypertension subtypes using multi-omics: A multi-centre, retrospective, data-driven study.

Background: Arterial hypertension is a major cardiovascular risk factor. Identification of secondary hypertension in its various forms is key to preventing and targeting treatment of cardiovascular complications. Simplified diagnostic tests are urgently required to distinguish primary and secondary hypertension to address the current underdiagnosis of the latter.

Predicting Hypertension Subtypes with Machine Learning Using Targeted Metabolites and Their Ratios.

Hypertension is a major global health problem with high prevalence and complex associated health risks. Primary hypertension (PHT) is most common and the reasons behind primary hypertension are largely unknown. Endocrine hypertension (EHT) is another complex form of hypertension with an estimated prevalence varying from 3 to 20% depending on the population studied.