{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T09:30:42Z","timestamp":1786440642647,"version":"build-2736575974"},"reference-count":53,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015391","name":"NPOO","doi-asserted-by":"publisher","award":["IP-UNIST-32"],"award-info":[{"award-number":["IP-UNIST-32"]}],"id":[{"id":"10.13039\/501100015391","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Med. Sci.","Medical Sciences"],"abstract":"<jats:p>Background: Inflammatory bowel disease (IBD) involves chronic immune activation, yet alterations in the cortisol awakening response (CAR) remain poorly defined. We compared cortisol dynamics in patients with IBD and healthy controls and explored associations with phenotype, endoscopic activity, and inflammation. Methods: This single-centre, cross-sectional case\u2013control study enrolled 100 patients with IBD (51 with ulcerative colitis [UC] and 49 with Crohn\u2019s disease [CD]) and 78 frequency-matched controls. Salivary cortisol was measured at awakening (C0), 30\u201345 min later (C1), and bedtime (C2); 97 patients and 78 controls met timing criteria. The absolute post-awakening increment (\u0394CAR) and area under the curve with respect to increase (AUCi) were calculated. Analyses included non-parametric tests, adjusted regression, mixed models, and multiplicity-corrected within-IBD comparisons and correlations. Results: Patients with IBD had lower C0 (median 0.478 vs. 1.067 \u00b5g\/dL) and C1 (0.850 vs. 1.950 \u00b5g\/dL; both p &lt; 0.001), whereas C2 was comparable (p = 0.819). \u0394CAR (0.130 vs. 0.461 \u00b5g\/dL) and AUCi (2.080 vs. 7.770 min\u00b7\u00b5g\/dL) were lower in IBD (both p &lt; 0.001); adjusted analyses confirmed this pattern. Cortisol metrics did not differ consistently by IBD subtype or endoscopic activity. Higher high-sensitivity C-reactive protein (hs-CRP) correlated positively with C0 (\u03c1 = 0.325; q = 0.041) and inversely with \u0394CAR (\u03c1 = \u22120.402; q = 0.002), AUCi (\u03c1 = \u22120.408; q = 0.002), and relative CAR (\u03c1 = \u22120.517; q &lt; 0.001). Conclusions: IBD was associated with attenuated CAR and lower morning cortisol output, with preserved bedtime concentrations. These cross-sectional findings support a relationship between systemic inflammation and altered early-morning HPA-axis dynamics but do not establish causality.<\/jats:p>","DOI":"10.3390\/medsci14040463","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T13:20:16Z","timestamp":1786108816000},"page":"463","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Blunted Cortisol Awakening Response in Patients with Inflammatory Bowel Disease: A Cross-Sectional Case\u2013Control Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1913-4565","authenticated-orcid":false,"given":"Marija Rafaela","family":"Plosnic Todoric","sequence":"first","affiliation":[{"name":"Department of Neonatology, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia"},{"name":"Evidence Based Medicine Doctoral Study, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3112-0656","authenticated-orcid":false,"given":"Roko","family":"Santic","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia"},{"name":"Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9696-3359","authenticated-orcid":false,"given":"Marko","family":"Kumric","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia"},{"name":"Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piero Marin","family":"Zivkovic","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3777-7350","authenticated-orcid":false,"given":"Ivna","family":"Olic","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7018-4947","authenticated-orcid":false,"given":"Doris","family":"Rusic","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5433-5063","authenticated-orcid":false,"given":"Marino","family":"Vilovic","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia"},{"name":"Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1715-0768","authenticated-orcid":false,"given":"Ivan","family":"Males","sequence":"additional","affiliation":[{"name":"Department of Abdominal Surgery, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Supe Domic","sequence":"additional","affiliation":[{"name":"Faculty of Health Studies, University of Split, Rudera Boskovica 35, 21000 Split, Croatia"},{"name":"Department of Laboratory Diagnostics, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1634-0635","authenticated-orcid":false,"given":"Josko","family":"Bozic","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia"},{"name":"Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1016\/S0140-6736(17)32448-0","article-title":"Worldwide Incidence and Prevalence of Inflammatory Bowel Disease in the 21st Century: A Systematic Review of Population-Based 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