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. The guideline includes a brief description of the genetics and molecular pathophysiology associated with each condition, the patients to be screened, and how to screen. Diagnostic and treatment approaches for patients with genetically determined diagnosis are presented. The recommendations apply to patients with genetically proven familial hyperaldosteronism and not to families with more than one case of primary aldosteronism without demonstration of a responsible pathogenic variant.

Indicación, realización y resultado del cateterismo de venas adrenales en pacientes con hiperaldosteronismo primario / Indication, performance and outcomes of adrenal vein sampling in patients with primary hyperaldosteronism

El hiperaldosteronismo primario (HAP) es una causa importante de hipertensión arterial (HTA) secundaria. El estudio del mismo precisa de una alta sospecha clínica, además de un estudio hormonal que confirme la hipersecreción hormonal. Es importante iniciar el tratamiento adecuado una vez se confirma el diagnóstico, y para ello es preciso demostrar si la hipersecreción hormonal es unilateral (pacientes que podrían ser tributarios a tratamiento quirúrgico) o bilateral (pacientes que son tributarios a tratamiento únicamente farmacológico). En el Hospital del Mar desde el año 2016 existe un equipo de trabajo multidisciplinar en el que participan nefrólogos, endocrinólogos, radiólogos y cirujanos para evaluar los casos con sospecha de hiperaldosteronismo y consensuar el mejor abordaje diagnóstico-terapéutico de estos pacientes, incluyendo la necesidad de cateterismo venoso adrenal, que es una técnica que en los últimos años se ha erigido como gold standard para el estudio del HAP. En el presente estudio recogemos la experiencia de nuestro centro en la realización de cateterismo venoso adrenal y en la utilidad de este para el manejo de tales pacientes (AU)

Primary hyperaldosteronism (PAH) is an important cause of secondary hypertension (HTN). The study of the same requires a high clinical suspicion in addition to a hormonal study that confirms hormonal hypersecretion. It is important to start the appropriate treatment once the diagnosis is confirmed, and for this is necessary to demonstrate whether the hormonal hypersecretion is unilateral (patients who could be candidates for surgical treatment) or bilateral (patients who are candidates for pharmacological treatment only). At the Hospital del Mar since 2016 there has been a multidisciplinary work team in which Nephrologists, Endocrinologists, Radiologists and Surgeons participate to evaluate cases with suspected hyperaldosteronism and agree on the best diagnostic-therapeutic approach for these patients, including the need for adrenal vein sampling, which is a technique that in recent years has become the gold standard for the study of PAH. In the present study we collect the experience of our center in performing adrenal vein catheterization and its usefulness for the management of these patients (AU)

The impact of superselective adrenal artery embolization on renal function in patients with primary aldosteronism: a prospective cohort study.

Superselective adrenal artery embolization (SAAE) is an effective treatment for patients with primary aldosteronism (PA). However, the impact of SAAE on renal function in the PA population remains uncertain. We investigated the estimated glomerular filtration rate (eGFR) and age, sex, body mass index, and diabetes-specific percentiles of eGFR residuals in 182 PA patients treated with SAAE in a prospective cohort from Nanchang SAAE in treating PA registry study. Data suggest that SAAE caused a significant decrease in eGFR from 91.9 ± 26.1 to 88.7 ± 24.1 ml/min/1.73 m2 (p < 0.05) after a median follow-up of 8 months in PA patients. Patients experienced a significant decrease in eGFR from 110.6 ± 18.9 to 103.8 ± 18.2 ml/min/1.73 m2 (p < 0.001) and a very slight increase from 71.1 ± 14.8 to 71.8 ± 17.8 ml/min/1.73 m2 (p = 0.770) with baseline eGFR ≥90 and <90 ml/min/1.73 m2, respectively. Patients with high eGFR residuals (glomerular hyperfiltration) experienced a significant decrease in their eGFR levels from 123.1 ± 22.6 to 105.0 ± 18.6 ml/min/1.73 m2 (p < 0.001). In contrast, there was no significant impact of SAAE on the eGFR of patients with normal or low eGFR residuals. The very early eGFR changes (24 h after SAAE) best predicted the effect of SAAE on eGFR changes after median of eight months in PA patients. On the whole, SAAE seems to have a beneficial impact on renal function in patients with PA, the results of which vary depending on the patient's baseline eGFR and glomerular hyperfiltration status.

Diagnosis and management of primary hyperaldosteronism in patients with hypertension: a practical approach endorsed by the British and Irish Hypertension Society.

Alongside the lack of homogeneity among international guidelines and consensus documents on primary hyperaldosteronism, the National UK guidelines on hypertension do not provide extensive recommendations regarding the diagnosis and management of this condition. Local guidelines vary from area to area, and this is reflected in the current clinical practice in the UK. In an attempt to provide support to the clinicians involved in the screening of subjects with hypertension and clinical management of suspected cases of primary hyperaldosteronism the following document has been prepared on the behalf of the BIHS Guidelines and Information Service Standing Committee. Through remote video conferences, the authors of this document reviewed an initial draft which was then circulated among the BIHS Executive members for feedback. A survey among members of the BIHS was carried out in 2022 to assess screening strategies and clinical management of primary hyperaldosteronism in the different regions of the UK. Feedback and results of the survey were then discussed and incorporated in the final document which was approved by the panel after consensus was achieved considering critical review of existing literature and expert opinions. Grading of recommendations was not performed in light of the limited available data from properly designed randomized controlled trials.

Follow-up care and assessment of comorbidities and complications in patients with primary aldosteronism: The clinical practice guideline of the Taiwan Society of aldosteronism.

Primary aldosteronism (PA) is the most common form of endocrine hypertension, characterized by excess aldosterone production that leads to an increased risk of cardiovascular events and target organ damage. Both adrenalectomy and medical treatment have shown efficacy in improving clinical outcomes and comorbidities associated with PA, including a specific subtype of PA with autonomous cortisol secretion (ACS). Understanding the comorbidities of PA and establishing appropriate follow-up protocols after treatment are crucial for physicians to enhance morbidity and mortality outcomes in patients with PA. Additionally, the screening for hypercortisolism prior to surgery is essential, as the prognosis of patients with coexisting PA and ACS differs from those with PA alone. In this review, we comprehensively summarize the comorbidities of PA, encompassing cardiovascular, renal, and metabolic complications. We also discuss various post-treatment outcomes and provide insights into the strategy for glucocorticoid replacement in patients with overt or subclinical hypercortisolism. This clinical practice guideline aims to equip medical professionals with up-to-date information on managing concurrent hypercortisolism, assessing treatment outcomes, and addressing comorbidities in patients with PA, thereby improving follow-up care.

A controlled trial of percutaneous adrenal arterial embolization for hypertension in patients with idiopathic hyperaldosteronism.

Our prior study has suggested that percutaneous superselective adrenal arterial embolization (SAAE) with ethanol reduces blood pressure in patients with primary aldosteronism. This study aimed to compare the efficacy of SAAE with mineralocorticoid receptor antagonists (MRA) in treating patients with idiopathic hyperaldosteronism. In this prospective, randomized, controlled trial, we randomly assigned patients with idiopathic hyperaldosteronism in a 1:1 ratio to undergo SAAE (n = 29) or receive MRA (n = 30) treatment. The primary endpoint was the change in mean 24-hour ambulatory systolic blood pressure at 6 months. The secondary endpoints included changes in office blood pressure, home blood pressure, correction of aldosterone-to-renin ratio, and adverse events at 6 months. The mean change in 24-h ambulatory systolic blood pressure from baseline to 6-month follow-up was significantly different between the two groups (-8.4 mmHg; 95% confidence interval, -15.2 to -2.1 mmHg; P < 0.01). Office, home, and ambulatory blood pressure reduction at 6 months was more pronounced in the SAAE group than the MRA group (all P < 0.05). Aldosterone-to-renin ratio was lower in the SAAE group than the MRA group at 1 and 3 months (both P < 0.01), while it had no difference between the two groups at 6 months. None of the patients experienced serious adverse events in the perioperative and 6-month follow-up periods. SAAE, as a hormonal debulking procedure, is superior to MRA in blood pressure control and correction of biochemical abnormalities in patients with idiopathic hyperaldosteronism.

Approach to the Patient: Reninoma.

A reninoma is a functional tumor of afferent arteriolar juxtaglomerular cells that secretes the enzyme renin, leading to hyperactivation of the renin-angiotensin-aldosterone system. Reninoma is a potentially curable cause of pathological secondary hyperaldosteronism that results in often severe hypertension and hypokalemia. The lack of suppression of plasma renin contrasts sharply with the much more common primary aldosteronism, but diagnosis is often prompted by screening for that condition. The major differential diagnosis of reninoma is renovascular hypertension. Fewer than 200 cases of reninoma have been described. Reninomas have been reported across a broad demographic but have a 2:1 predilection for women, often of childbearing age. Aldosterone receptor blockade, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers offer effective medical management but are contraindicated in pregnancy, so surgical curative resection is ideal. The current optimal imaging and biochemical workup of reninoma and management approach (ideally, tumor excision with subtotal renal resection) are described.

Treating Primary Aldosteronism-Induced Hypertension: Novel Approaches and Future Outlooks.

Primary aldosteronism (PA) is the most common cause of secondary hypertension and is associated with increased morbidity and mortality when compared with blood pressure-matched cases of primary hypertension. Current limitations in patient care stem from delayed recognition of the condition, limited access to key diagnostic procedures, and lack of a definitive therapy option for nonsurgical candidates. However, several recent advances have the potential to address these barriers to optimal care. From a diagnostic perspective, machine-learning algorithms have shown promise in the prediction of PA subtypes, while the development of noninvasive alternatives to adrenal vein sampling (including molecular positron emission tomography imaging) has made accurate localization of functioning adrenal nodules possible. In parallel, more selective approaches to targeting the causative aldosterone-producing adrenal adenoma/nodule (APA/APN) have emerged with the advent of partial adrenalectomy or precision ablation. Additionally, the development of novel pharmacological agents may help to mitigate off-target effects of aldosterone and improve clinical efficacy and outcomes. Here, we consider how each of these innovations might change our approach to the patient with PA, to allow more tailored investigation and treatment plans, with corresponding improvement in clinical outcomes and resource utilization, for this highly prevalent disorder.

A Prospective Observational Study of Factors Affecting the Change in Quality of Life in Patients With Primary Aldosteronism After Treatment.

OBJECTIVE: To explore the changes in the health-related quality of life (HRQoL) in patients with primary aldosteronism (PA) after standardized treatment and determine the effects of different variables on the change in the HRQoL of patients. METHODS: A total of 116 patients with PA were prospectively included from November 2020 to March 2022. Data were collected at their initial diagnosis and the follow-up after 12 months of treatment, including demographic and clinical data and the scores of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). The scores of each dimension of SF-36 of patients before and after treatment were compared, and the factors affecting their change in the quality of life were analyzed using multiple linear regression. RESULTS: After standardized treatment, the aldosterone-to-renin ratio (Z = -4.967, P < .001), systolic blood pressure (t = 8.985, P < .001), and diastolic blood pressure (t = 7.233, P < .001) of patients with PA decreased compared with baseline, and hypokalemia was effectively corrected (χ2 = 69.014, P < .001). In terms of quality of life, 6 of 8 dimensions of SF-36 and the total score of SF-36 significantly improved at 1-year follow-up compared with baseline (all P < .05). The results of multiple linear regression showed that the improvement in the HRQoL in patients with PA after standardized treatment was correlated with the change in the blood potassium level (P = .007) and systolic blood pressure (P = .003). CONCLUSION: Correction of hypokalemia and control of diastolic blood pressure are essential factors contributing to the improvement in the HRQoL in patients with PA regardless of the standardized treatment received.

Primary aldosteronism: Practical recommendations for treatment and follow-up / Hiperaldosteronismo primario: recomendaciones prácticas de tratamiento y seguimiento

Primary aldosteronism (PA) is the most common cause of secondary arterial hypertension. For unilateral cases, surgery offers the possibility of cure, with unilateral adrenalectomy being the treatment of choice, whereas bilateral forms of PA are treated mainly with mineralocorticoid receptor antagonists (MRA). The goals of treatment for PA due to either unilateral or bilateral adrenal disease include reversal of the adverse cardiovascular effects of hyperaldosteronism, normalization of serum potassium in patients with hypokalemia, and normalization of blood pressure. The Primary Aldosteronism Surgery Outcome group (PASO) published a study defining clinical and biochemical outcomes based on blood pressure and correction of hypokalemia and aldosterone to renin ratio (ARR) levels for patients undergoing total unilateral adrenalectomy for unilateral PA. In this review, we provide several practical recommendations for the medical and surgical management and follow-up of patients with PA. (AU)

El hiperaldosteronismo primario (HAP) es la causa más frecuente de hipertensión arterial secundaria. Para los casos unilaterales, la cirugía ofrece la posibilidad de curación, siendo la adrenalectomía unilateral el tratamiento de elección, mientras que las formas bilaterales de HAP se tratan principalmente con antagonistas del receptor de mineralocorticoides (ARM). Los objetivos del tratamiento del HAP debido a enfermedad suprarrenal unilateral o bilateral incluyen la reversión de los efectos cardiovasculares adversos del hiperaldosteronismo, la normalización del potasio sérico en pacientes con hipopotasemia y la normalización de la presión arterial. El grupo Primary Aldosteronism Surgery Outcome (PASO) publicó un estudio que define los resultados clínicos y bioquímicos en función de la presión arterial y la corrección de la hipopotasemia y los niveles del cociente aldosterona/renina (ARR) para pacientes sometidos a adrenalectomía unilateral total por HAP unilateral. En esta revisión ofrecemos varias recomendaciones prácticas para el manejo y el seguimiento médico-quirúrgico de los pacientes con HAP. (AU)

Increasing rates of referrals for investigation of primary aldosteronism at a tertiary centre.

AIM: To describe the frequency and characteristics of patients referred for specialist investigation of primary aldosteronism (PA) in the lower North Island over a 5-year period, and the outcomes of those who received treatment. METHODS: Patients who underwent confirmatory testing or treatment for PA at Wellington Regional Hospital were retrospectively identified and data were collected from electronic clinical records. RESULTS: There has been a five-fold increase in both referrals and confirmatory testing for PA in 2021 compared to 2015. Compared to patients without PA, those eventually diagnosed with PA had a higher ARR, serum sodium, antihypertensive requirement and cardiovascular disease prevalence, as well as lower serum renin, potassium and GFR (all p <0.05), but similar blood pressure. Complete or partial clinical success was achieved in 96% of surgically treated patients compared with 70% of medically treated patients. Thirty-nine percent of patients experienced minor adverse effects with spironolactone and only one significant adverse event was experienced perioperatively. CONCLUSIONS: The rate of referrals and confirmatory testing for PA are increasing in our region. Adrenalectomy and mineralocorticoid antagonist therapy are both safe and effective treatments, although minor adverse effects were common with spironolactone.

Primary aldosteronism: Practical recommendations for treatment and follow-up.

Primary aldosteronism (PA) is the most common cause of secondary arterial hypertension. For unilateral cases, surgery offers the possibility of cure, with unilateral adrenalectomy being the treatment of choice, whereas bilateral forms of PA are treated mainly with mineralocorticoid receptor antagonists (MRA). The goals of treatment for PA due to either unilateral or bilateral adrenal disease include reversal of the adverse cardiovascular effects of hyperaldosteronism, normalization of serum potassium in patients with hypokalemia, and normalization of blood pressure. The Primary Aldosteronism Surgery Outcome group (PASO) published a study defining clinical and biochemical outcomes based on blood pressure and correction of hypokalemia and aldosterone to renin ratio (ARR) levels for patients undergoing total unilateral adrenalectomy for unilateral PA. In this review, we provide several practical recommendations for the medical and surgical management and follow-up of patients with PA.

Key to the Treatment of Primary Aldosteronism in Secondary Hypertension: Subtype Diagnosis.

PURPOSE OF REVIEW: Primary aldosteronism (PA) is a leading global cause of secondary hypertension. Subtyping diagnosis of PA is the key to surgery, but accurate classification of PA is crucial but challenging in clinical diagnosis and treatment. The purpose of this review is to provide a summary of current literature and propose subtyping diagnosis flow chart to help us classify PA quickly and accurately. RECENT FINDINGS: Early diagnosis and accurate typing are essential for the timely treatment and appropriate management of PA. For most patients, adrenal venous sampling (AVS) is the central choice for typing diagnosis, but AVS is invasive and difficult to promote effectively. CT can help identify unilateral typical adenomas in select patients to avoid AVS. New radionuclide imaging has shown value in the diagnosis and classification of PA, which distinguishes adrenocortical hyperplasia from adenoma and can replace AVS in some patients. Accurately diagnosing unilateral PA is crucial for determining the appropriate treatment strategy for PA. The simple flow chart of PA subtyping diagnosis based on the current literature needs to be verified and evaluated by follow-up researches.

Therapeutic management of congenital forms of endocrine hypertension.

Congenital forms of endocrine hypertension are rare and potentially life-threatening disorders, primarily caused by genetic defects affecting adrenal steroid synthesis and activation pathways. These conditions exhibit diverse clinical manifestations, which can be distinguished by their unique molecular mechanisms and steroid profiles. Timely diagnosis and customized management approach are crucial to mitigate unfavorable outcomes associated with uncontrolled hypertension and other related conditions. Treatment options for these disorders depend on the distinct underlying pathophysiology, which involves specific pharmacological therapies or surgical adrenalectomy in some instances. This review article summarizes the current state of knowledge on the therapeutic management of congenital forms of endocrine hypertension, focusing on familial hyperaldosteronism (FH), congenital adrenal hyperplasia, apparent mineralocorticoid excess, and Liddle syndrome. We provide an overview of the genetic and molecular pathogenesis underlying each disorder, describe the clinical features, and discuss the various therapeutic approaches available and their risk of adverse effects, aiming to improve outcomes in patients with these rare and complex conditions.

Primary aldosteronism 2.0: an update for clinicians on diagnosis and treatment.

Primary aldosteronism (PA), characterized by inappropriately high concentrations of the adrenal-derived hormone aldosterone, is the most common endocrine cause of arterial hypertension. As compared with individuals with essential hypertension, patients with PA have a significantly increased cardiovascular risk that cannot be fully reversed by common antihypertensive treatment because of blood pressure-independent deleterious effects of aldosterone. Measurement of the aldosterone to renin ratio (ARR), reflecting the degree of aldosterone excess, is the classic screening test for PA, but thresholds for an elevated ARR vary substantially and are arbitrary, as there exists a wide disease continuum that spans from preclinical stages to overt PA. Treatment approaches for PA with either mineralocorticoid receptor antagonists for bilateral disease or unilateral adrenalectomy for aldosterone-producing adenomas (APA) are highly effective to mitigate the excess cardiovascular risk associated with PA. Subtype classification according to the dichotomous concept of unilateral PA, mainly due to APAs, vs bilateral PA, mainly due to bilateral adrenal hyperplasia, has been recently challenged by advances in the pathophysiologic understanding and therapeutic spectrum of PA. The implementation of current PA guidelines into clinical routine is extremely poor, as reflected by the fact that most patients suffering from PA remain undiagnosed and probably untreated. Pragmatic approaches are required to address this public health problem. In this review, we present an up­to­date overview on the clinical significance, diagnosis, and treatment of PA, with the aim to provide guidance for clinicians regarding the management of this disease, paying particular attention to its feasible implementation into daily clinical routine.

2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism.

Primary aldosteronism (PA) is a common, yet underdiagnosed cause of secondary hypertension. It is characterized by an overproduction of aldosterone, leading to hypertension and/or hypokalemia. Despite affecting between 5.9% and 34% of patients with hypertension, PA is frequently missed due to a lack of clinical awareness and systematic screening, which can result in significant cardiovascular complications. To address this, medical societies have developed clinical practice guidelines to improve the management of hypertension and PA. The Korean Endocrine Society, drawing on a wealth of research, has formulated new guidelines for PA. A task force has been established to prepare PA guidelines, which encompass epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and follow-up care. The Korean clinical guidelines for PA aim to deliver an evidence-based protocol for PA diagnosis, treatment, and patient monitoring. These guidelines are anticipated to ease the burden of this potentially curable condition.

Primary Aldosteronism.

Primary aldosteronism is the underlying cause of hypertension in primary care settings in approximately 6% of cases, and it is even more common in patients with resistant hypertension. However, it is estimated that only about 2% of patients who have risk factors for primary aldosteronism have been formally tested or diagnosed. The first step in the diagnosis of primary aldosteronism is case detection and involves testing patients who are at risk, including individuals with resistant hypertension, as well as those with well-controlled hypertension and a first-degree relative with primary aldosteronism, hypokalemia, an adrenal nodule, atrial fibrillation, obstructive sleep apnea, or a family history of an early stroke (i.e., younger than 40 years). Initial case detection is performed by simultaneously measuring plasma aldosterone concentration and plasma renin activity; an elevated aldosterone-renin ratio (greater than 30) indicates independent aldosterone secretion (i.e., aldosteronism). After a positive case detection, confirmatory testing should be performed. Confirmatory tests include the captopril challenge, oral or intravenous salt loading, or fludrocortisone suppression. Results are positive if aldosterone levels remain high after interventions that suppress or interrupt physiologic production of aldosterone. If the confirmatory test is positive, adrenal computed tomography and adrenal vein sampling should be performed to differentiate unilateral from bilateral adrenal production of aldosterone. Patients with unilateral primary aldosteronism should undergo adrenalectomy, whereas those with bilateral production should be treated with mineralocorticoid receptor antagonists, such as spironolactone or eplerenone.

Primary aldosteronism: molecular medicine meets public health.

Primary aldosteronism is the most common single cause of hypertension and is potentially curable when only one adrenal gland is the culprit. The importance of primary aldosteronism to public health derives from its high prevalence but huge under-diagnosis (estimated to be <1% of all affected individuals), despite the consequences of poor blood pressure control by conventional therapy and enhanced cardiovascular risk. This state of affairs is attributable to the fact that the tools used for diagnosis or treatment are still those that originated in the 1970-1990s. Conversely, molecular discoveries have transformed our understanding of adrenal physiology and pathology. Many molecules and processes associated with constant adrenocortical renewal and interzonal metamorphosis also feature in aldosterone-producing adenomas and aldosterone-producing micronodules. The adrenal gland has one of the most significant rates of non-silent somatic mutations, with frequent selection of those driving autonomous aldosterone production, and distinct clinical presentations and outcomes for most genotypes. The disappearance of aldosterone synthesis and cells from most of the adult human zona glomerulosa is the likely driver of the mutational success that causes aldosterone-producing adenomas, but insights into the pathways that lead to constitutive aldosterone production and cell survival may open up opportunities for novel therapies.