{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:23Z","timestamp":1792790363554,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,13]]},"group-title":"Endocrinology (including Diabetes Mellitus and Metabolic Disease)","reference-count":25,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T00:00:00Z","timestamp":1789257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases","award":["R01DK115392"],"award-info":[{"award-number":["R01DK115392"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Heart, Lung, and Blood Institute Division of Intramural Research","award":["K24HL180292"],"award-info":[{"award-number":["K24HL180292"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Heart, Lung, and Blood Institute Division of Intramural Research","award":["R01HL153004"],"award-info":[{"award-number":["R01HL153004"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Heart, Lung, and Blood Institute Division of Intramural Research","award":["K23HL159279"],"award-info":[{"award-number":["K23HL159279"]}],"id":[{"id":"https:\/\/ror.org\/023ny1p48","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Accumulating evidence suggests that the prevalence of hypercortisolism in patients with cardiometabolic risk factors is much higher than previously thought. This study aimed to evaluate the prevalence of ACTH-independent hypercortisolism across the spectrum of cardiometabolic risk.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Participants were prospectively recruited into three cohorts to undergo protocolized assessment of adrenal physiology:1) normotensive participants; 2) participants with hypertension and obesity, but without diabetes; 3) participants with diabetes and overweight\/obesity. All participants (n=216) underwent overnight 1 mg dexamethasone suppression testing followed by cosyntropin stimulation test, and 24-hour urine free cortisol (UFC) testing. ACTH-independent hypercortisolism was defined as post-dexamethasone serum cortisol &gt;1.8 \u03bcg\/dL (50 nmol\/L) with a concomitant post-dexamethasone ACTH \u226410 pg\/mL (2.2 pmol\/L).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Result<\/jats:title>\n                  <jats:p>\n                    16 of 216 (7.4%) participants were found to have ACTH-independent hypercortisolism, including 5.6% (4\/71) in the normotensive cohort, 6.2% (5\/81) in the hypertension-obesity cohort and 10.9% (7\/64) in the diabetes-obesity cohort. Age, body mass index, hemoglobin A1c, blood pressure, renal function, morning ACTH, and 24-hour UFC were similar among those with and without ACTH-independent hypercortisolism. Following cosyntropin stimulation, those with ACTH-independent hypercortisolism had higher stimulated cortisol levels (greater ACTH- dependent responses) when compared to those without ACTH-independent hypercortisolism: 25.8\u00b14.5 versus 20.6\u00b14.1 \u03bcg\/dL (711\u00b1124 v. 568\u00b1113 nmol\/L) (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.001).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In this prospective study, the prevalence of ACTH-independent hypercortisolism paralleled the burden of cardiometabolic risk features. ACTH-independent hypercortisolism was associated with greater ACTH-stimulable cortisol production, identifying a unique biochemical phenotype. These findings reveal new insights into cortisol pathophysiology as a function of ACTH and cardiometabolic risk profiles.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.11.26362842","type":"posted-content","created":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T21:45:11Z","timestamp":1789335911000},"source":"Crossref","is-referenced-by-count":0,"title":["ACTH-independent hypercortisolism across the cardiometabolic spectrum"],"prefix":"10.64898","author":[{"given":"Andrew J.","family":"Newman","sequence":"first","affiliation":[{"name":"Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Metabolism, Brigham and Women\u2019s Hospital\/Mass General Brigham, Harvard Medical School, Boston MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanan","family":"Mahrokhian","sequence":"additional","affiliation":[{"name":"Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Metabolism, Brigham and Women\u2019s Hospital\/Mass General Brigham, Harvard Medical School, Boston MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Hanna","sequence":"additional","affiliation":[{"name":"Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Metabolism, Brigham and Women\u2019s Hospital\/Mass General Brigham, Harvard Medical School, Boston MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Hsuan","family":"Tsai","sequence":"additional","affiliation":[{"name":"Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Metabolism, Brigham and Women\u2019s Hospital\/Mass General Brigham, Harvard Medical School, Boston MA, USA"},{"name":"Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9fanie","family":"Parisien-La Salle","sequence":"additional","affiliation":[{"name":"Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Metabolism, Brigham and Women\u2019s Hospital\/Mass General Brigham, Harvard Medical School, Boston MA, USA"},{"name":"Division of Endocrinology, Department of Medicine, Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CHUM), Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manaporn","family":"Payanundana","sequence":"additional","affiliation":[{"name":"Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Metabolism, Brigham and Women\u2019s Hospital\/Mass General Brigham, Harvard Medical School, Boston MA, USA"},{"name":"Division of Endocrinology and Metabolism, Department of Medicine, Phramongkutklao Hospital, and Phramongkutklao College of Medicine, Bangkok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard 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