{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:31:17Z","timestamp":1778646677887,"version":"3.51.4"},"reference-count":26,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T00:00:00Z","timestamp":1571184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Grants-in-Aid for Scientific Research","doi-asserted-by":"crossref","award":["19H03708"],"award-info":[{"award-number":["19H03708"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Grants-in-Aid for Scientific Research","doi-asserted-by":"crossref","award":["18K08464"],"award-info":[{"award-number":["18K08464"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Grants-in-Aid for Scientific Research","doi-asserted-by":"crossref","award":["19K07635"],"award-info":[{"award-number":["19K07635"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Grants-in-Aid for Scientific Research","doi-asserted-by":"crossref","award":["18K07439"],"award-info":[{"award-number":["18K07439"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007428","name":"Naito Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008667","name":"SENSHIN Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008667","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008273","name":"NOVARTIS Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008273","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Medical Institute of Bioregulation at Kyushu University"},{"name":"Donated Fund of Next Generation Hormone Academy for Human Health & Longevity"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Hashimoto\u2019s thyroiditis is the most common cause of hypothyroidism. Patients usually respond well to oral synthetic thyroxine (levothyroxine); however, for unknown reasons some individuals present with treatment-resistant Hashimoto thyroiditis. In cases of cancer and certain infectious diseases, the ATP binding cassette (ABC) transporters have been implicated in multidrug resistance, and we hypothesized and investigated a role of ABC transporters in drug-resistant Hashimoto\u2019s thyroiditis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Case Description<\/jats:title>\n                  <jats:p>The patient whose case we report had a history of Hashimoto\u2019s thyroiditis, immune thrombocytopenia, and refractory hypertension, with varying treatment resistance to the oral medications prescribed for each condition. In order to establish or exclude a genetic basis for her illness, we examined the patient\u2019s gene expression profiles using peripheral blood leukocytes, and found that ABCG2\/BCRPexpression was significantly high compared with healthy volunteers. Also, the increased daunomycin efflux capacity of our patient\u2019s lymphocytes was successfully inhibited by fumitremorgin C, a specific ABCG2\/BCRP inhibitor, and the patient\u2019s level of thyroid-stimulating hormone increased by 248.6% after administration of intact levothyroxine tablets but decreased by 45.1% when tablets were crushed. Her average blood pressure decreased from 166.3\/108.5 mmHg to 125.9\/78.8 mmHg when switching from intact to crushed losartan tablets.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>High expression and accelerated efflux transporter activity of ABCG2\/BCRP in the small intestine are expected to contribute to the ineffectiveness of orally administered intact tablets in cases with treatment-resistant Hashimoto\u2019s thyroiditis, and crushed tablets can be more effective for some of these patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgz073","type":"journal-article","created":{"date-parts":[[2019,10,15]],"date-time":"2019-10-15T22:43:08Z","timestamp":1571179388000},"page":"399-406","source":"Crossref","is-referenced-by-count":7,"title":["A Case of Hashimoto\u2019s Thyroiditis with Multiple Drug Resistance and High Expression of Efflux Transporters"],"prefix":"10.1210","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8887-7867","authenticated-orcid":false,"given":"Tomohiko","family":"Yoshida","sequence":"first","affiliation":[{"name":"Department of Diabetes, Metabolism and Endocrinology, School of Medicine, International University of Health and Welfare, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akitoshi","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ai","family":"Tamura","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Hematology, and Gerontology, Graduate School of Medicine, Chiba University, Chiba, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiichiro","family":"Higuchi","sequence":"additional","affiliation":[{"name":"Department 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