{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T23:05:17Z","timestamp":1769555117665,"version":"3.49.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lenvatinib\u2010related hypothyroidism occurs in 16%\u201322% of patients with hepatocellular carcinoma and may affect treatment management. Previous studies have reported elevated serum thyroid stimulating hormone (TSH) levels despite levothyroxine therapy, indicating the need for research on the optimal levothyroxine dose during lenvatinib therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>We aimed to explore the effect of lenvatinib on thyroid function, focusing on lenvatinib pharmacokinetics and factors influencing hypothyroidism development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>A retrospective cohort study involving 56 patients with hepatocellular carcinoma treated with lenvatinib was conducted at the Mie University Hospital. The primary outcome was grade \u2265\u20092 hypothyroidism. Demographic data, treatment details, and clinical outcomes were analyzed to identify factors associated with lenvatinib\u2010related hypothyroidism. In addition, we assessed the levothyroxine dose administered during treatment and the dose required to achieve TSH levels\u2009&lt;\u200910\u2009mIU\/L. Twelve patients (21%) developed hypothyroidism during lenvatinib therapy. The median levothyroxine dose and time to onset of hypothyroidism were 25.0 [25.0\u201350.0]\u2009\u03bcg\/day and 81.0 [15.0\u2013208.0]\u2009days, respectively. Levothyroxine therapy was initiated at either a low or recommended dose, with 10 patients achieving TSH levels\u2009&lt;\u200910\u2009mIU\/L. Significant predictors of hypothyroidism included age\u2009\u2264\u200963\u2009years and a higher daily lenvatinib dose (\u2265\u20090.152\u2009mg\/kg\/day).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Initiation of levothyroxine therapy, even at lower doses, may be effective in managing lenvatinib\u2010related hypothyroidism. Underweight patients (e.g., body weight\u2009&lt;\u200950\u2009kg) require particular attention due to their increased susceptibility to hypothyroidism. Even though this study has limitations such as a small sample size and the lack of multivariate analysis, it provides valuable information for managing lenvatinib\u2010related hypothyroidism.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cnr2.70461","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T03:45:46Z","timestamp":1768967146000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Course and Risk Factors of Lenvatinib\u2010Related Hypothyroidism in Hepatocellular Carcinoma: A Retrospective Cohort Study"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1190-6540","authenticated-orcid":false,"given":"Chihiro","family":"Shiraishi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences for Health Crisis Management, Faculty of Pharmaceutical Sciences Fukuoka University  Fukuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5272-9560","authenticated-orcid":false,"given":"Hideo","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Mie University Hospital  Mie Japan"},{"name":"Department of Clinical Pharmaceutics, Division of Clinical Medical Science Mie University Graduate School of Medicine  Mie Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1933-8592","authenticated-orcid":false,"given":"Yuki","family":"Asai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Mie University Hospital  Mie Japan"},{"name":"Department of Clinical Pharmaceutics, Division of Clinical Medical Science Mie University Graduate School of Medicine  Mie Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6445-4410","authenticated-orcid":false,"given":"Takuya","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Mie University Hospital  Mie Japan"},{"name":"Department of Clinical Pharmaceutics, Division of Clinical Medical Science Mie University Graduate School of Medicine  Mie Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23131"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-5270"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/638747"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/2045-824X-6-18"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2024.14464"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-016-1199-8"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1406470"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ando.2018.07.003"},{"issue":"164","key":"e_1_2_14_10_1","first-page":"241","article-title":"Hypothyroidism in Adults: Levothyroxine if Warranted by Clinical and Laboratory Findings, Not for Simple TSH Elevation","volume":"24","year":"2015","journal-title":"Prescrire International"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/985780"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/725410"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2013.0241"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000531881"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.1361"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2012.402"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.917"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-019-01078-2"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-011-1949-5"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12876-021-02038-3"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2008.12.034"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1159\/000356507"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ19-0140"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdr275"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2014.11.002"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpem-2018-0519"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.13752"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpc.13926"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2017.05.002"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-1191-7953"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2020.0393"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep26174"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000350"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.68.6.750"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-25-6-723"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.18.5.660"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-1354"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12010049"}],"container-title":["Cancer Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cnr2.70461","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cnr2.70461","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cnr2.70461","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T10:11:53Z","timestamp":1769508713000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cnr2.70461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/cnr2.70461"],"URL":"https:\/\/doi.org\/10.1002\/cnr2.70461","archive":["Portico"],"relation":{},"ISSN":["2573-8348","2573-8348"],"issn-type":[{"value":"2573-8348","type":"print"},{"value":"2573-8348","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-05-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70461"}}