Stowasser, Michael

BACKGROUND: Primary aldosteronism (PA) is a common and treatable cause of hypertension, yet data on the durability of medical treatment response beyond the first year are limited. Using the PA medical treatment outcomes framework, we evaluated long-term biochemical and clinical outcomes and factors associated with treatment response. METHODS: We conducted an international, multicenter, observational cohort study across 27 centers on 4 continents. Adults with PA treated with mineralocorticoid receptor antagonists and/or epithelial sodium channel blockers between 2016 and 2021 were included if follow-up data were available at ≥12 months. Biochemical and clinical responses were classified as complete, partial, or absent using PA medical treatment outcomes criteria. Ordinal logistic regression identified determinants of a favorable treatment response. RESULTS: The cohort included 1292 patients (47.5% women, mean age 52 years) with a median follow-up of 34 months (interquartile range, 21–51). At ≥12 months, 58.3% achieved a complete biochemical response, and 20.8% achieved a complete clinical response, with only 5% showing no response. Determinants of a favorable biochemical response included lower aldosterone and lateralization index, and higher renin and potassium levels at baseline. In those taking spironolactone, a higher daily dose was also associated with a favorable biochemical response. Determinants of a favorable clinical response included female sex, lower body mass index, shorter duration of hypertension, and absence of hypertension-mediated organ damage. CONCLUSIONS: Targeted medical therapy for PA can deliver sustained biochemical and clinical benefits. Early disease detection and adequate dose titration are highly actionable determinants of long-term treatment success.

Abstract Background Primary aldosteronism (PA) is a common treatable cause of hypertension. When caused by unilateral adrenal disease, it is potentially curable by adrenalectomy. However, specialized tests and other factors may delay definitive treatment. We assessed the time to adrenalectomy (TTA) for patients worldwide. Methods We conducted an international, multicentre retrospective study involving 39 centres from 15 countries to determine the total time taken from the first presentation to adrenalectomy and the intervals between each stage (screening, confirmatory, subtyping, and adrenalectomy). We included patients with PA who underwent adrenalectomy from January 1, 2018, to October 30, 2022. Post-adrenalectomy outcomes were evaluated using the Primary Aldosteronism Surgery Outcome criteria. We performed multivariable quantile and linear regression to identify characteristics associated with longer TTA. Results We included 861 patients, mean age 49.3 ± 11.1 years, and 44.5% were women. Overall median TTA was 13.5 months, IQR: 6.6-24.5. Median intervals were 0.1 months (screening), 1.0 months (confirmatory), 4.1 months (subtyping), and 4.3 months (adrenalectomy). On multivariable analysis, median TTA was increased by 5.4 months for each additional adrenal vein sampling (AVS) procedure. Other factors associated with longer TTA included adrenalectomy post-COVID-19, younger age, and additional screening tests. Compared with countries with routine AVS, those without AVS had a shorter TTA (6.1 vs 15.1 months, P < .001), but greater likelihood of absent/partial biochemical success post-adrenalectomy (27.4% vs 12.4%, P < .001). Conclusion Primary aldosteronism management is time-consuming worldwide, especially for subtyping tests and adrenalectomy. While omitting AVS reduces overall time, patients are less likely to achieve biochemical cure post-adrenalectomy.

Abstract 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. Objective To develop an updated guideline that provides a practical, clinical approach to identifying and managing PA to improve diagnosis rates and encourage targeted treatment. Methods The Guideline Development Panel (GDP), composed of a multidisciplinary panel of clinical experts and experts in systemic review methodology, used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to define 10 questions related to the diagnosis and treatment of PA. Systematic reviews were conducted for each question. The GDP used the GRADE Evidence to Decision (EtD) framework to consider contextual factors, such as stakeholder values and preferences, costs and required resources, cost-effectiveness, acceptability, feasibility, and the potential impact on health equity. Results We suggest that all individuals with hypertension be screened for PA by measuring aldosterone and renin and determining the aldosterone to renin ratio, and that subsequent clinical care be guided by the results. We suggest that individuals with PA receive PA-specific therapy, either medical or surgical. In individuals who screen positive for PA, we suggest (1) commencement of PA-specific medical therapy in individuals who do not desire or are not candidates for surgery and in situations where the probability of lateralizing PA (excess aldosterone produced by one adrenal) is low based on screening results; and (2) aldosterone suppression testing in situations when screening results indicate an intermediate probability for lateralizing PA and individualized decision making confirms a desire to pursue eligibility for surgical therapy. In those who test positive by aldosterone suppression testing, and in those in whom screening results show a high probability of lateralizing PA (obviating the need for aldosterone suppression testing), we suggest adrenal lateralization with computed tomography scanning and adrenal venous sampling prior to deciding the treatment approach (medical vs surgical). In all individuals with PA and an adrenal adenoma, we suggest performing a 1-mg overnight dexamethasone suppression test. We suggest the use of mineralocorticoid receptor antagonists (MRAs) over epithelial sodium-channel (ENaC) inhibitors in the medical treatment of PA. We suggest the use of spironolactone over other MRAs, given its lower cost and greater availability; however, all MRAs, when titrated to equivalent potencies, are anticipated to have similar efficacy in treating PA. Thus, MRAs with greater mineralocorticoid receptor specificity and fewer androgen/progesterone receptor-mediated side effects may be preferred in some situations. In individuals receiving MRA therapy, we suggest monitoring renin and, in those whose hypertension remains uncontrolled and renin is suppressed, titrating the MRA to increase renin. Conclusion These recommendations provide a practical framework for the diagnosis and treatment of PA. They are based on currently available literature and take into consideration outcomes that are important to key stakeholders. The goal is to increase identification of individuals with PA and, by initiating PA-specific medical or surgical therapy, improve blood pressure control and reduce PA-associated adverse cardiovascular events. The guidelines also highlight important knowledge gaps in PA diagnosis and management.

Background Accumulating evidence suggests that primary aldosteronism (PA) is associated with several features of the metabolic syndrome, in particular with obesity, type 2 diabetes mellitus, and dyslipidemia. Whether these manifestations are primarily linked to aldosterone-producing adenoma (APA) or bilateral idiopathic hyperaldosteronism (IHA) remains unclear. The aim of the present study was to investigate differences in metabolic parameters between APA and IHA patients and to assess the impact of treatment on these clinical characteristics. Methods We conducted a retrospective multicenter study including 3566 patients with APA or IHA of Caucasian and Asian origin. We compared the prevalence of metabolic disorders between APA and IHA patients at the time of diagnosis and 1-year post-intervention, with special references to sex differences. Furthermore, correlations between metabolic parameters and plasma aldosterone, renin, or plasma cortisol levels after 1 mg dexamethasone (DST) were performed. Results As expected, APA patients were characterized by higher plasma aldosterone and lower serum potassium levels. Only female IHA patients demonstrated significantly worse metabolic parameters than age-matched female APA patients, which were associated with lower cortisol levels upon DST. One-year post-intervention, female adrenalectomized patients showed deterioration of their lipid profile, when compared to patients treated with mineralocorticoid receptor antagonists. Plasma aldosterone levels negatively correlated with the BMI only in APA patients. Conclusions Metabolic alterations appear more prominent in women with IHA. Although IHA patients have worse metabolic profiles, a correlation with cortisol autonomy is documented only in APAs, suggesting an uncoupling of cortisol action from metabolic traits in IHA patients.

AbstractObjective:To develop clinical practice guidelines for the management of patients with primary aldosteronism.Participants:The Task Force included a chair, selected by the Clinical Guidelines Subcommittee of the Endocrine Society, six additional experts, a methodologist, and a medical writer. The guideline was cosponsored by American Heart Association, American Association of Endocrine Surgeons, European Society of Endocrinology, European Society of Hypertension, International Association of Endocrine Surgeons, International Society of Endocrinology, International Society of Hypertension, Japan Endocrine Society, and The Japanese Society of Hypertension. The Task Force received no corporate funding or remuneration.Evidence:We searched for systematic reviews and primary studies to formulate the key treatment and prevention recommendations. We used the Grading of Recommendations, Assessment, Development, and Evaluation group criteria to describe both the quality of evidence and the strength of recommendations. We used “recommend” for strong recommendations and “suggest” for weak recommendations.Consensus Process:We achieved consensus by collecting the best available evidence and conducting one group meeting, several conference calls, and multiple e-mail communications. With the help of a medical writer, the Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and Council successfully reviewed the drafts prepared by the Task Force. We placed the version approved by the Clinical Guidelines Subcommittee and Clinical Affairs Core Committee on the Endocrine Society's website for comments by members. At each stage of review, the Task Force received written comments and incorporated necessary changes.Conclusions:For high-risk groups of hypertensive patients and those with hypokalemia, we recommend case detection of primary aldosteronism by determining the aldosterone-renin ratio under standard conditions and recommend that a commonly used confirmatory test should confirm/exclude the condition. We recommend that all patients with primary aldosteronism undergo adrenal computed tomography as the initial study in subtype testing and to exclude adrenocortical carcinoma. We recommend that an experienced radiologist should establish/exclude unilateral primary aldosteronism using bilateral adrenal venous sampling, and if confirmed, this should optimally be treated by laparoscopic adrenalectomy. We recommend that patients with bilateral adrenal hyperplasia or those unsuitable for surgery should be treated primarily with a mineralocorticoid receptor antagonist.

Abstract Primary aldosteronism (PA) is a common form of endocrine hypertension previously believed to account for less than 1% of hypertensive patients. Hypokalemia was considered a prerequisite for pursuing diagnostic tests for PA. Recent studies applying the plasma aldosterone/plasma renin activity ratio (ARR) as a screening test have reported a higher prevalence. This study is a retrospective evaluation of the diagnosis of PA from clinical centers in five continents before and after the widespread use of the ARR as a screening test. The application of this strategy to a greater number of hypertensives led to a 5- to 15-fold increase in the identification of patients affected by PA. Only a small proportion of patients (between 9 and 37%) were hypokalemic. The annual detection rate of aldosterone-producing adenoma (APA) increased in all centers (by 1.3–6.3 times) after the wide application of ARR. Aldosterone-producing adenomas constituted a much higher proportion of patients with PA in the four centers that employed adrenal venous sampling (28–50%) than in the center that did not (9%). In conclusion, the wide use of the ARR as a screening test in hypertensive patients led to a marked increase in the detection rate of PA.