Thyroid Hormone Kinetics: Prognostic Significance of Dynamic TSH and Free T3 Changes in Critically Ill Patients

Thyroid Hormone Kinetics: Prognostic Significance of Dynamic TSH and Free T3 Changes in Critically Ill Patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Thyroid Hormone Kinetics: Prognostic Significance of Dynamic TSH and Free T3 Changes in Critically Ill Patients Yakup Özgüngör, Burak Emre Gilik, Emre Karagöz, Mensure Çakırgöz This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8218667/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Non-thyroidal illness syndrome is frequent in critically ill patients, but the prognostic value of dynamic changes in thyroid function tests remains unclear. This study evaluated whether serial measurements of thyroid-stimulating hormone (TSH) and free triiodothyronine (FT3) provide additional predictive value for 30-day mortality beyond conventional severity scores in ICU patients. Methods : This single-center retrospective observational study included 74 adult patients treated for ≥72 hours in a general ICU who had TSH and FT3 measured within 24 hours of admission and again at 48–72 hours. Demographic characteristics, comorbidities, APACHE II, SOFA, modified NUTRIC (mNUTRIC) scores, and routine laboratory data (including albumin, CRP, and lactate) were recorded. The primary outcome was 30-day mortality. Between-group comparisons were performed using t-tests, Mann–Whitney U, and Chi-square tests. Variables significant in univariate analyses were entered into binary logistic regression models, and predictive performance was assessed using receiver operating characteristic (ROC) curves and the Youden index. Results: The mean age was 68.7 ± 14.7 years, and 41.9% (n = 31) of patients died within 30 days. Non-survivors had higher APACHE II, SOFA, and mNUTRIC scores and lower albumin, lymphocyte count, and second FT3 levels compared with survivors (all p ≤ 0.003). Baseline FT3 and TSH were not associated with mortality, whereas both the second FT3 measurement and the ΔT3 (second–first FT3) were strongly predictive. Second FT3 <1.63 pg/mL yielded an AUC of 0.835 (sensitivity 77%, specificity 74%), and a ΔT3 log ratio threshold of –0.09 (≈20% early FT3 decline) produced an AUC of 0.835 (sensitivity 71%, specificity 81%). The APACHE II + ΔT3 (numeric) model showed the best discrimination (AUC 0.921; sensitivity 87.1%, specificity 81.4%), outperforming APACHE II alone (AUC 0.861). Conclusions : In critically ill adults, dynamic T3 kinetics—particularly early decline in FT3 within the first 72 hours—provide substantial incremental prognostic value for 30-day mortality beyond APACHE II. Serial FT3 monitoring may help identify high-risk patients whose endocrine adaptation to critical illness is failing. Critical Care & Emergency Medicine Non-thyroidal illness syndrome (NTIS) Thyroid function tests Thyroid-stimulating hormone 30-day mortality Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8218667","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":551548530,"identity":"5b82af7c-772b-42d6-b95a-4b51a8025a58","order_by":0,"name":"Yakup Özgüngör","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9UlEQVRIiWNgGAWjYBACxgYGBmYEtwKImZkbSNFyBqSFEb8WEEBoYWyDGYNPefvhh48LKursNtxuv/i4cl5tNH87UMuPim24HdaTZmw84wxb8oY7Z4oNz247njvjMGMDY8+Z23j8ksMmzdvGk2xwIydNsnHbsdwGoBZmxjY8WvrfgLRIQLXMOZY7n6CWGWBbDOwMbqQfk2xsqMndQFjLM5BfEhIkb+QwGzYcO5C7EajlID6/GPYng0PMnu9G+sOHDTV1ufPOHz744EcFHi0NEDqxgYHHAEgfBvMO4FQPBPJQ2p6Bgf0BkK7Dp3gUjIJRMApGKAAAkr9eHq81qngAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-1370-1696","institution":"","correspondingAuthor":true,"prefix":"","firstName":"Yakup","middleName":"","lastName":"Özgüngör","suffix":""},{"id":551548886,"identity":"5318c9c5-9d9d-4de6-857d-79c1052fb680","order_by":1,"name":"Burak Emre Gilik","email":"","orcid":"https://orcid.org/0000-0002-6277-3530","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Burak","middleName":"Emre","lastName":"Gilik","suffix":""},{"id":551548887,"identity":"c85a3479-a18a-432e-afc6-e0a19ad0f582","order_by":2,"name":"Emre Karagöz","email":"","orcid":"https://orcid.org/0000-0002-3831-9565","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Emre","middleName":"","lastName":"Karagöz","suffix":""},{"id":551548888,"identity":"440a82d4-0102-4a2d-ad15-04753510155e","order_by":3,"name":"Mensure Çakırgöz","email":"","orcid":"https://orcid.org/0000-0001-7687-0924","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Mensure","middleName":"","lastName":"Çakırgöz","suffix":""}],"badges":[],"createdAt":"2025-11-27 06:40:52","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-8218667/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8218667/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":97137155,"identity":"894417af-33d8-4cc2-9e2d-6c25df40ff83","added_by":"auto","created_at":"2025-12-01 09:57:24","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":414477,"visible":true,"origin":"","legend":"","description":"","filename":"CLINICSD2501427R11.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8218667/v1_covered_deb407b5-b297-4a4e-a4e5-08db584e3893.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eThyroid Hormone Kinetics: Prognostic Significance of Dynamic TSH and Free T3 Changes in Critically Ill Patients\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Non-thyroidal illness syndrome (NTIS), Thyroid function tests, Thyroid-stimulating hormone, 30-day mortality","lastPublishedDoi":"10.21203/rs.3.rs-8218667/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8218667/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Non-thyroidal illness syndrome is frequent in critically ill patients, but the prognostic value of dynamic changes in thyroid function tests remains unclear. This study evaluated whether serial measurements of thyroid-stimulating hormone (TSH) and free triiodothyronine (FT3) provide additional predictive value for 30-day mortality beyond conventional severity scores in ICU patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: This single-center retrospective observational study included 74 adult patients treated for ≥72 hours in a general ICU who had TSH and FT3 measured within 24 hours of admission and again at 48–72 hours. Demographic characteristics, comorbidities, APACHE II, SOFA, modified NUTRIC (mNUTRIC) scores, and routine laboratory data (including albumin, CRP, and lactate) were recorded. The primary outcome was 30-day mortality. Between-group comparisons were performed using t-tests, Mann–Whitney U, and Chi-square tests. Variables significant in univariate analyses were entered into binary logistic regression models, and predictive performance was assessed using receiver operating characteristic (ROC) curves and the Youden index.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The mean age was 68.7 ± 14.7 years, and 41.9% (n = 31) of patients died within 30 days. Non-survivors had higher APACHE II, SOFA, and mNUTRIC scores and lower albumin, lymphocyte count, and second FT3 levels compared with survivors (all p ≤ 0.003). Baseline FT3 and TSH were not associated with mortality, whereas both the second FT3 measurement and the ΔT3 (second–first FT3) were strongly predictive. Second FT3 \u0026lt;1.63 pg/mL yielded an AUC of 0.835 (sensitivity 77%, specificity 74%), and a ΔT3 log ratio threshold of –0.09 (≈20% early FT3 decline) produced an AUC of 0.835 (sensitivity 71%, specificity 81%). The APACHE II + ΔT3 (numeric) model showed the best discrimination (AUC 0.921; sensitivity 87.1%, specificity 81.4%), outperforming APACHE II alone (AUC 0.861).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: In critically ill adults, dynamic T3 kinetics—particularly early decline in FT3 within the first 72 hours—provide substantial incremental prognostic value for 30-day mortality beyond APACHE II. Serial FT3 monitoring may help identify high-risk patients whose endocrine adaptation to critical illness is failing.\u003c/p\u003e","manuscriptTitle":"Thyroid Hormone Kinetics: Prognostic Significance of Dynamic TSH and Free T3 Changes in Critically Ill Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-28 08:10:54","doi":"10.21203/rs.3.rs-8218667/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c5c59584-6ab7-4c13-98e2-b05b97c4c3ba","owner":[],"postedDate":"November 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":58691596,"name":"Critical Care \u0026 Emergency Medicine"}],"tags":[],"updatedAt":"2026-01-04T14:08:35+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-28 08:10:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8218667","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8218667","identity":"rs-8218667","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}