{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:24:20Z","timestamp":1791815060973,"version":"4.3.4"},"reference-count":75,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Renin-independent aldosterone production in normotensive people increases risk for developing hypertension. In parallel, normotensive adrenal glands frequently harbor aldosterone-producing micronodules with pathogenic somatic mutations known to induce primary aldosteronism (PA). A deeper understanding of these phenomena would inform the origins of PA and its role in hypertension pathogenesis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>Prospectively recruited normotensives underwent detailed characterization of PA features via the following: oral sodium suppression test to evaluate renin-independent aldosterone production, dexamethasone suppression and adrenocorticotropic hormone-stimulation tests to evaluate adrenocorticotropic hormone-mediated aldosterone production, and 24-hour ambulatory blood pressure monitoring. The magnitude of renin-independent aldosterone production was defined via tertiles of 24-hour urinary aldosterone production during the oral sodium suppression test to create unbiased categorizations of the magnitude of PA. Serum aldosterone, serum 18-hybrid steroids, urine tetrahydroaldosterone (biomarkers of aldosterone synthase activity), urinary potassium, and blood pressure (biomarkers of mineralocorticoid receptor activation) were evaluated across tertiles.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              There was a spectrum of autonomous, nonsuppressible, and renin-independent production of aldosterone, 18-hybrid steroids, and 24-hour urinary tetrahydroaldosterone (\n              <jats:italic>P<\/jats:italic>\n              -trend &lt;0.01). Correspondingly, there was a continuum of adrenocorticotropic hormone-mediated aldosterone production and 18-hybrid steroid production that also paralleled renin-independent aldosterone production. The spectrum of PA pathophysiology was associated with higher ambulatory daytime systolic BP (\n              <jats:italic>P<\/jats:italic>\n              -trend &lt;0.05), even within the normotensive range, and greater urinary potassium excretion (\n              <jats:italic>P<\/jats:italic>\n              -trend &lt;0.05), indicating a continuum of mineralocorticoid receptor activation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>The pathophysiologic continuum of PA, characterized by renin-independent and adrenocorticotropic hormone-mediated aldosterone production, and enhanced aldosterone synthase and mineralocorticoid receptor activity, is evident in normotensive people. These findings provide mechanistic explanations to implicate PA in the pathogenesis of a substantial proportion of hypertension.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/hypertensionaha.124.24153","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T10:05:01Z","timestamp":1733911501000},"page":"306-318","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":32,"title":["Characterizing the Origins of Primary Aldosteronism"],"prefix":"10.1161","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6647-639X","authenticated-orcid":true,"given":"Jenifer M.","family":"Brown","sequence":"first","affiliation":[{"name":"Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension (J.M.B., B.H., L.C.T., J.M., Y.M.N., A.J.N., A.V.)."},{"name":"Division of Cardiovascular Medicine (J.M.B.)."},{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (J.M.B., B.H., L.C.T., J.M., Y.M.N., A.J.N., A.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2824-903X","authenticated-orcid":true,"given":"Brooke","family":"Honzel","sequence":"additional","affiliation":[{"name":"Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension (J.M.B., B.H., L.C.T., J.M., Y.M.N., A.J.N., A.V.)."},{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (J.M.B., B.H., L.C.T., J.M., Y.M.N., A.J.N., A.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura C.","family":"Tsai","sequence":"additional","affiliation":[{"name":"Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension (J.M.B., B.H., L.C.T., J.M., Y.M.N., A.J.N., A.V.)."},{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (J.M.B., B.H., L.C.T., J.M., Y.M.N., A.J.N., A.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Milks","sequence":"additional","affiliation":[{"name":"Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension (J.M.B., B.H., L.C.T., J.M., Y.M.N., A.J.N., A.V.)."},{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (J.M.B., B.H., L.C.T., J.M., Y.M.N., A.J.N., A.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne M.","family":"Neibuhr","sequence":"additional","affiliation":[{"name":"Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension (J.M.B., B.H., L.C.T., J.M., Y.M.N., A.J.N., A.V.)."},{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (J.M.B., B.H., L.C.T., J.M., Y.M.N., A.J.N., A.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8326-1964","authenticated-orcid":true,"given":"Andrew J.","family":"Newman","sequence":"additional","affiliation":[{"name":"Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension (J.M.B., B.H., L.C.T., J.M., Y.M.N., A.J.N., A.V.)."},{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (J.M.B., B.H., L.C.T., J.M., Y.M.N., A.J.N., A.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Cherney","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor (M.C., D.G.S., R.J.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Stouffer","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor (M.C., D.G.S., R.J.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6815-6181","authenticated-orcid":true,"given":"Richard J.","family":"Auchus","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology and Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor (M.C., D.G.S., R.J.A.)."},{"name":"Endocrinology and Metabolism Section, LTC Charles S. Kettles Veterans Affairs Medical Center, Ann Arbor, MI (R.J.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0314-9252","authenticated-orcid":true,"given":"Anand","family":"Vaidya","sequence":"additional","affiliation":[{"name":"Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension (J.M.B., B.H., L.C.T., J.M., Y.M.N., A.J.N., A.V.)."},{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (J.M.B., B.H., L.C.T., J.M., Y.M.N., A.J.N., A.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.08952"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-3867"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.7326\/M20-0065"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgae145"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-4061"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa033263"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000258554.87444.91"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.7326\/M17-0882"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.066389"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-3353"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1505529112"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/js.2017-00134"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.028201"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.7326\/M17-2237"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.122.19134"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.124.070039"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2016.00072"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa703"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab420"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-17-0563"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-116-1-6"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.04453"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.118.11243"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1055\/a-2054-1062"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2022.111720"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-1088"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.00662"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1511939"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvac049"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(65)90357-0"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab924"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1042\/cs0570409"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-52-2-214"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2009.03469.x"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(89)90046-0"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.050896"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.816108"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.15006"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.817411"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.023082"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac352"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00257-3"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(18)30071-8"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/ehjcvp\/pvab031"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41371-023-00891-1"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-19-0215"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2025845"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2110956"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41440-020-00570-5"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2213169"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.16029"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)02408-X"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15713"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1964.03070160037008"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1972.03650060041007"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1972.03650060047008"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.133.2.205"},{"key":"e_1_3_3_59_2","first-page":"54","article-title":"The inappropriate secretion of aldosterone associated with adrenal hyperplasia.","volume":"42","author":"Grim CE","year":"1976","unstructured":"Grim CE, Keitzer WF, Esterly JA, Longo DL. The inappropriate secretion of aldosterone associated with adrenal hyperplasia. Univ Mich Med Cent J. 1976;42:54\u201359.","journal-title":"Univ Mich Med Cent J"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2001.01253.x"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-07-0037"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-08-0711"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.644382"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-15-0148"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/355262a0"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-0594"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-2384"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2015.251199"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.13866"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41440-023-01347-2"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.124.23029"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.115.06186"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.16209"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.01.052"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.14063"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2004.12.005"}],"container-title":["Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/HYPERTENSIONAHA.124.24153","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T19:02:37Z","timestamp":1736967757000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/HYPERTENSIONAHA.124.24153"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":75,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1161\/HYPERTENSIONAHA.124.24153"],"URL":"https:\/\/doi.org\/10.1161\/hypertensionaha.124.24153","relation":{},"ISSN":["0194-911X","1524-4563"],"issn-type":[{"value":"0194-911X","type":"print"},{"value":"1524-4563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"2024-10-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}