{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T20:53:32Z","timestamp":1793566412154,"version":"4.5.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Superior outcomes after surgical treatment over medical treatment for primary aldosteronism (PA) has been reported in small-scale clinical studies, but no solid conclusion has been drawn as results of large randomized trials are lacking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a search of PubMed, MEDLINE, Embase and Cochrane Library for randomized or observational studies that investigated cardiovascular outcomes in patients with PA undergoing medical <jats:italic>versus<\/jats:italic> surgical treatment. Meta-analyses of both composite and individual outcomes were conducted. Risks of bias of the included studies were assessed with Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) checklist. Trial sequential analysis (TSA) was performed to control the risk of random errors and assess whether the results in our meta-analysis were conclusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 12 studies, including a total of 6148 PA patients, were included in the meta-analysis. The results of meta-analyses demonstrated lower incidence of composite cardiovascular outcomes among PA patients who underwent surgical treatment over medical treatment (odds ratio (OR): 0.49). Surgical treatment also led to less incidence of persistence of hypertension (OR of non-cure hypertension: 0.31). Fewer major cardiovascular events and mortality events were observed (OR: 0.60) after surgical treatment. TSA result showed that the required information size was 2151 and the cumulative Z curve crossed the futility boundary and reached the required information size.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Superior performance of surgical treatment over medical treatment is confirmed with meta-analyses in terms of lower incidences of composite cardiovascular outcomes and non-cure of hypertension. Hence, adrenalectomy could now be concluded as the treatment of choice for lateralized PA.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2021.644260","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T06:22:30Z","timestamp":1621232550000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Composite Cardiovascular Outcomes in Patients With Primary Aldosteronism Undergoing Medical Versus Surgical Treatment: A Meta-Analysis"],"prefix":"10.3389","volume":"12","author":[{"given":"Wei-Chieh","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Ying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Hung","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff S.","family":"Chueh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.5555\/uri:pii:0022214355900482","article-title":"Presidential Address. I. Painting Background. II. Primary Aldosteronism, a New Clinical Syndrome","volume":"45","author":"Conn","year":"1955","journal-title":"J Lab Clin Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.07.059","article-title":"A Prospective Study of the Prevalence of Primary Aldosteronism in 1,125 Hypertensive Patients","volume":"48","author":"Rossi","year":"2006","journal-title":"J Am Coll Cardiol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.01.052","article-title":"Prevalence and Clinical Manifestations of Primary Aldosteronism Encountered in Primary Care Practice","volume":"69","author":"Monticone","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2007.02775.x","article-title":"Primary Aldosteronism: Renaissance of a Syndrome","volume":"66","author":"Young","year":"2007","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.162.15.1707","article-title":"Inappropriate Drug Prescribing in Home-Dwelling, Elderly Patients: A Population-Based Survey","volume":"162","author":"Pitkala","year":"2002","journal-title":"Arch Intern Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2805","article-title":"Long-Term Cardio- and Cerebrovascular Events in Patients With Primary Aldosteronism","volume":"98","author":"Mulatero","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.01060","article-title":"Cardiovascular Complications Associated With Primary Aldosteronism: A Controlled Cross-Sectional Study","volume":"62","author":"Savard","year":"2013","journal-title":"Hypertension"},{"key":"B8","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.tem.2008.01.006","article-title":"Primary Aldosteronism: Cardiovascular, Renal and Metabolic Implications","volume":"19","author":"Rossi","year":"2008","journal-title":"Trends Endocrinol Metab"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1055\/s-0043-122602","article-title":"Subtyping of Patients With Primary Aldosteronism: An Update","volume":"49","author":"Lenders","year":"2017","journal-title":"Horm Metab Res"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.095448","article-title":"Long-Term Cardiac Effects of Adrenalectomy or Mineralocorticoid Antagonists in Patients With Primary Aldosteronism","volume":"50","author":"Catena","year":"2007","journal-title":"Hypertension"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1246185","article-title":"Mineralocorticoid Antagonists Treatment Versus Surgery in Primary Aldosteronism","volume":"42","author":"Catena","year":"2010","journal-title":"Horm Metab Res"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-4061","article-title":"The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline","volume":"101","author":"Funder","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"B13","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1016\/j.jfma.2017.06.004","article-title":"Case Detection and Diagnosis of Primary Aldosteronism - The Consensus of Taiwan Society of Aldosteronism","volume":"116","author":"Wu","year":"2017","journal-title":"J Formos Med Assoc"},{"key":"B14","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.jfma.2018.01.006","article-title":"Targeted Treatment of Primary Aldosteronism - The Consensus of Taiwan Society of Aldosteronism","volume":"118","author":"Huang","year":"2019","journal-title":"J Formos Med Assoc"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2010.05.006","article-title":"Consequences of Adrenal Venous Sampling in Primary Hyperaldosteronism and Predictors of Unilateral Adrenal Disease","volume":"211","author":"Mathur","year":"2010","journal-title":"J Am Coll Surg"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1210\/jc.86.3.1066","article-title":"Comparison of Adrenal Vein Sampling and Computed Tomography in the Differentiation of Primary Aldosteronism","volume":"86","author":"Magill","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-1851","article-title":"Risk Factors Associated With a Low Glomerular Filtration Rate in Primary Aldosteronism","volume":"94","author":"Reincke","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-013-2871-3","article-title":"Medical or Surgical Therapy for Primary Aldosteronism: Post-Treatment Follow-Up as a Surrogate Measure of Comparative Outcomes","volume":"20","author":"Kline","year":"2013","journal-title":"Ann Surg Oncol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1210\/jc.2017-01442","article-title":"Quality of Life in Primary Aldosteronism: A Comparative Effectiveness Study of Adrenalectomy and Medical Treatment","volume":"103","author":"Velema","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"B20","article-title":"Cardiovascular Changes in Patients With Primary Aldosteronism After Surgical or Medical Treatment","volume":"35","author":"Bernini","year":"2012","journal-title":"J Endocrinol Invest"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.93136","article-title":"Steroid Metabolome Analysis Reveals Prevalent Glucocorticoid Excess in Primary Aldosteronism","volume":"2","author":"Arlt","year":"2017","journal-title":"JCI Insight"},{"key":"B22","doi-asserted-by":"publisher","first-page":"i4919","DOI":"10.1136\/bmj.i4919","article-title":"Robins-I: A Tool for Assessing Risk of Bias in non-Randomised Studies of Interventions","volume":"355","author":"Sterne","year":"2016","journal-title":"BMJ"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.2307\/2530245","article-title":"A Multiple Testing Procedure for Clinical Trials","volume":"35","author":"O\u2019Brien","year":"1979","journal-title":"Biometrics"},{"key":"B24","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s12874-017-0315-7","article-title":"Trial Sequential Analysis in Systematic Reviews With Meta-Analysis","volume":"17","author":"Wetterslev","year":"2017","journal-title":"BMC Med Res Methodol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1507\/endocrj.EJ13-0353","article-title":"Prognosis of Primary Aldosteronism in Japan: Results From a Nationwide Epidemiological Study","volume":"61","author":"Miyake","year":"2014","journal-title":"Endocr J"},{"key":"B26","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1007\/BF03349173","article-title":"Diurnal Blood Pressure Pattern in Patients With Primary Aldosteronism","volume":"29","author":"Zacharieva","year":"2006","journal-title":"J Endocrinol Invest"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2007.33","article-title":"Cardiovascular Outcomes in Patients With Primary Aldosteronism After Treatment","volume":"168","author":"Catena","year":"2008","journal-title":"Arch Intern Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.01316","article-title":"Long-Term Control of Arterial Hypertension and Regression of Left Ventricular Hypertrophy With Treatment of Primary Aldosteronism","volume":"62","author":"Rossi","year":"2013","journal-title":"Hypertension"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e3280108e6f","article-title":"Aldosterone as a Key Mediator of the Cardiometabolic Syndrome in Primary Aldosteronism: An Observational Study","volume":"25","author":"Giacchetti","year":"2007","journal-title":"J Hypertens"},{"key":"B30","doi-asserted-by":"publisher","first-page":"32103","DOI":"10.1038\/srep32103","article-title":"Long Term Outcome of Aldosteronism After Target Treatments","volume":"6","author":"Wu","year":"2016","journal-title":"Sci Rep"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ16-0530","article-title":"Outcomes Analysis of Surgical and Medical Treatments for Patients With Primary Aldosteronism","volume":"64","author":"Park","year":"2017","journal-title":"Endocr J"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/cen.14351","article-title":"Outcomes in Unilateral Primary Aldosteronism After Surgical or Medical Therapy","volume":"94","author":"Puar","year":"2021","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/cen.14351","article-title":"Outcomes After Adrenalectomy for Unilateral Primary Aldosteronism: An International Consensus on Outcome Measures and Analysis of Remission Rates in an International Cohort","volume":"5","author":"Williams","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.9744","article-title":"Systematic Review of Surgery and Outcomes in Patients With Primary Aldosteronism","volume":"102","author":"Muth","year":"2015","journal-title":"Br J Surg"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-008-9513-0","article-title":"Retroperitoneoscopic Adrenalectomy in Conn\u2019s Syndrome Caused by Adrenal Adenomas or Nodular Hyperplasia","volume":"32","author":"Walz","year":"2008","journal-title":"World J Surg"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2007.09.001","article-title":"Good Blood Pressure Control on Antihypertensives, Not Only Response to Spironolactone, Predicts Improved Outcome After Adrenalectomy for Aldosteronoma","volume":"142","author":"Zarnegar","year":"2007","journal-title":"Surgery"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1159\/000347028","article-title":"Factors Affecting Complete Hypertension Cure After Adrenalectomy for Aldosterone-Producing Adenoma: Outcomes in a Large Series","volume":"90","author":"Zhang","year":"2013","journal-title":"Urol Int"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)64028-1","article-title":"Laparoscopic Management of Primary Hyperaldosteronism: Clinical Experience With 212 Cases","volume":"169","author":"Meria","year":"2003","journal-title":"J Urol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-1733","article-title":"Prevalence and Characteristics of the Metabolic Syndrome in Primary Aldosteronism","volume":"91","author":"Fallo","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"B40","doi-asserted-by":"publisher","first-page":"130042","DOI":"10.1530\/EDM-13-0042","article-title":"Benign Adrenal Adenomas Secreting Excess Mineralocorticoids and Glucocorticoids","volume":"2013","author":"Yoon","year":"2013","journal-title":"Endocrinol Diabetes Metab Case Rep"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e32834937f3","article-title":"Concurrent Primary Aldosteronism and Subclinical Cortisol Hypersecretion: A Prospective Study","volume":"29","author":"Fallo","year":"2011","journal-title":"J Hypertens"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-0736","article-title":"Insulin Sensitivity in Patients With Primary Aldosteronism: A Follow-Up Study","volume":"91","author":"Catena","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000001361","article-title":"Risk of New-Onset Diabetes Mellitus in Primary Aldosteronism: A Population Study Over 5 Years","volume":"35","author":"Wu","year":"2017","journal-title":"J Hypertens"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-1763","article-title":"Improved Quality of Life, Blood Pressure, and Biochemical Status Following Laparoscopic Adrenalectomy for Unilateral Primary Aldosteronism","volume":"95","author":"Sukor","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"B45","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1111\/j.1749-6632.2002.tb04413.x","article-title":"Primary Aldosteronism: Management Issues","volume":"970","author":"Young","year":"2002","journal-title":"Ann N Y Acad Sci"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3109\/07853890.2013.785234","article-title":"Diagnosis and Management of Primary Aldosteronism: An Updated Review","volume":"45","author":"Chao","year":"2013","journal-title":"Ann Med"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1291\/hypres.29.883","article-title":"Clinical Characteristics of Aldosterone-Producing Microadenoma, Macroadenoma, and Idiopathic Hyperaldosteronism in 93 Patients With Primary Aldosteronism","volume":"29","author":"Omura","year":"2006","journal-title":"Hypertens Res"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.644260\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T06:22:34Z","timestamp":1621232554000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.644260\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,17]]},"references-count":47,"alternative-id":["10.3389\/fendo.2021.644260"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2021.644260","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,17]]},"article-number":"644260"}}