{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T12:44:35Z","timestamp":1774356275615,"version":"3.50.1"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,25]],"date-time":"2021-09-25T00:00:00Z","timestamp":1632528000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,25]],"date-time":"2021-09-25T00:00:00Z","timestamp":1632528000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Med Case Reports"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Resistance to thyroid hormone is a rare autosomal dominant disorder characterized by reduced responsiveness to thyroid hormone and can cause syndrome of inappropriate secretion of thyroid stimulating hormone. Although Graves\u2019 disease is a common autoimmune thyroid disorder, the coexistence of these two diseases is extremely rare and makes the diagnosis and treatment complicated, leading to the delayed diagnosis of resistance to thyroid hormone. We describe the case of a Japanese man with resistance to thyroid hormone coexisting with Graves\u2019 disease, in which the correct diagnosis of resistance to thyroid hormone was delayed by masking of the signs of syndrome of inappropriate secretion of thyroid stimulating hormone, with final diagnosis 30\u00a0years after the initial treatment for Graves\u2019 disease.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>A 30-year-old Japanese man presented with diffuse goiter and thyrotoxicosis. Anti-thyroid stimulating hormone receptor antibody was positive. He was diagnosed with Graves\u2019 disease. Anti-thyroid medication was chosen as the initial treatment for Graves\u2019 disease. However, this treatment failed to normalize the free triiodothyronine, free thyroxine, and thyroid stimulating hormone levels. His thyroid hormone levels indicated syndrome of inappropriate secretion of thyroid stimulating hormone. After cessation of methimazole treatment by remission of Graves\u2019 disease, his state of syndrome of inappropriate secretion of thyroid stimulating hormone persisted. Magnetic resonance imaging revealed no pituitary tumor lesions. The results of thyroid stimulating hormone-releasing hormone stimulation test showed a normal response of thyroid stimulating hormone. He was suspected to have resistance to thyroid hormone. Direct sequencing analysis of the thyroid hormone receptor \u03b2 gene identified a heterozygous missense mutation, R282S. Coexistence of resistance to thyroid hormone with Graves\u2019 disease was confirmed. He has no signs of thyrotoxic symptoms, and is capable in activities of daily living at the present time.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>We described a rare case of resistance to thyroid hormone simultaneously existing with Graves\u2019 disease. This case demonstrated that these diseases can coexist, and indicated some of the difficulties in diagnosis of resistance to thyroid hormone with coexisting Graves\u2019 disease. The diagnosis of resistance to thyroid hormone did not become apparent until after anti-hyperthyroidism treatment. Although rare, careful follow-up after the initial treatment of Graves\u2019 disease is necessary. The coexistence of these two diseases should be considered in patients showing occasional syndrome of inappropriate secretion of thyroid stimulating hormone.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13256-021-03061-4","type":"journal-article","created":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T23:06:46Z","timestamp":1632524806000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Graves\u2019 disease coexisted with resistance to thyroid hormone: a case report"],"prefix":"10.1186","volume":"15","author":[{"given":"Hiroshi","family":"Akahori","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rika","family":"Usuda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,9,25]]},"reference":[{"issue":"3","key":"3061_CR1","first-page":"348","volume":"14","author":"S Refetoff","year":"1993","unstructured":"Refetoff S, Weiss RE, Usala SJ. The syndromes of resistance to thyroid hormone. Endocr Rev. 1993;14(3):348\u20139.","journal-title":"Endocr Rev"},{"issue":"2","key":"3061_CR2","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.beem.2007.03.005","volume":"21","author":"S Refetoff","year":"2007","unstructured":"Refetoff S, Dumitrescu AM. Syndromes of reduced sensitivity to thyroid hormone: genetic defects in hormone receptors, cell transporters and deiodination. Best Pract Res Clin Endocrinol Metab. 2007;21(2):277\u2013305.","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"12","key":"3061_CR3","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1210\/mend-2-12-1217","volume":"2","author":"SJ Usala","year":"1988","unstructured":"Usala SJ, Bale AE, Gesundheit N, Weinberger C, Lash RW, Wondisford FE, McBride W, Weintraub BD. Tight linkage between the syndrome of generalized thyroid hormone resistance and the human c-erbA beta gene. Mol Endocrinol. 1988;2(12):1217\u201320.","journal-title":"Mol Endocrinol"},{"issue":"6","key":"3061_CR4","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1172\/JCI115542","volume":"88","author":"R Parrilla","year":"1991","unstructured":"Parrilla R, Mixson AJ, McPherson JA, McClaskey JH, Weintraub BD. Characterization of seven novel mutations of the c-erbA beta gene in unrelated kindreds with generalized thyroid hormone resistance. Evidence for two \u201chot spot\u201d regions of the ligand binding domain. J Clin Invest. 1991;88(6):2123\u201330.","journal-title":"J Clin Invest"},{"issue":"46","key":"3061_CR5","doi-asserted-by":"publisher","first-page":"30175","DOI":"10.1074\/jbc.273.46.30175","volume":"273","author":"JD Safer","year":"1998","unstructured":"Safer JD, Cohen RN, Hollenberg AN, Wondisford FE. Defective release of corepressor by hinge mutants of the thyroid hormone receptor found in patients with resistance to thyroid hormone. J Biol Chem. 1998;273(46):30175\u201382.","journal-title":"J Biol Chem"},{"issue":"12","key":"3061_CR6","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.1210\/mend-4-12-1988","volume":"4","author":"A Sakurai","year":"1990","unstructured":"Sakurai A, Miyamoto T, Refetoff S, DeGroot LJ. Dominant negative transcriptional regulation by a mutant thyroid hormone receptor-beta in a family with generalized resistance to thyroid hormone. Mol Endocrinol. 1990;4(12):1988\u201394.","journal-title":"Mol Endocrinol"},{"issue":"2","key":"3061_CR7","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1210\/jcem-27-2-279","volume":"27","author":"S Refetoff","year":"1967","unstructured":"Refetoff S, DeWind LT, DeGroot LJ. Familial syndrome combining deaf-mutism, stuppled epiphyses, goiter and abnormally high PBI: possible target organ refractoriness to thyroid hormone. J Clin Endocrinol Metab. 1967;27(2):279\u201394.","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"3061_CR8","doi-asserted-by":"publisher","first-page":"339","DOI":"10.7326\/0003-4819-95-3-339","volume":"95","author":"BD Weintraub","year":"1981","unstructured":"Weintraub BD, Gershengorn MC, Kourides IA, Fein H. Inappropriate secretion of thyroid-stimulating hormone. Ann Intern Med. 1981;95(3):339\u201351.","journal-title":"Ann Intern Med"},{"key":"3061_CR9","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1067\/S0022-3476(03)00184-7","volume":"143","author":"SH Lafranchi","year":"2003","unstructured":"Lafranchi SH, Snyder DB, Sesser DE, Skeels MR, Singh N, Brent GA, Nelson JC. Follow-up of newborns with elevated screening T4 concentrations. J Pediatr. 2003;143:296\u2013301.","journal-title":"J Pediatr"},{"issue":"6","key":"3061_CR10","first-page":"610","volume":"17","author":"P Beck-Peccoz","year":"1996","unstructured":"Beck-Peccoz P, Brucker-Davis F, Persani L, Smallridge RC, Weintraub BD. Thyrotropin-secreting pituitary tumors. Endocr Rev. 1996;17(6):610\u201338.","journal-title":"Endocr Rev"},{"issue":"2","key":"3061_CR11","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1089\/thy.2009.0175","volume":"20","author":"T Sivakumar","year":"2010","unstructured":"Sivakumar T, Chaidarun S. Resistance to thyroid hormone in a patient with coexisting Graves\u2019 disease. Thyroid. 2010;20(2):213\u20136.","journal-title":"Thyroid"},{"issue":"8","key":"3061_CR12","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1507\/endocrj.K10E-066","volume":"57","author":"H Sato","year":"2010","unstructured":"Sato H. Clinical features of primary hyperthyroidism caused by Graves\u2019 disease admixed with resistance to thyroid hormone (P453T). Endocr J. 2010;57(8):687\u201392.","journal-title":"Endocr J"},{"issue":"2","key":"3061_CR13","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1007\/s12020-011-9491-0","volume":"40","author":"K Ogawa","year":"2011","unstructured":"Ogawa K, Yoshida M, Hayashi Y, Murata Y, Miyata M, Oiso Y. A rare case of resistance to thyroid hormone coexisting with Graves\u2019 disease. Endocrine. 2011;40(2):318\u20139.","journal-title":"Endocrine"},{"issue":"5","key":"3061_CR14","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1056\/NEJM200502033520523","volume":"352","author":"S Fukata","year":"2005","unstructured":"Fukata S, Brent GA, Sugawara M. Resistance to thyroid hormone in Hashimoto\u2019s thyroiditis. N Engl J Med. 2005;352(5):517\u20138.","journal-title":"N Engl J Med"},{"issue":"4","key":"3061_CR15","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1007\/BF03347207","volume":"28","author":"DY Aksoy","year":"2005","unstructured":"Aksoy DY, Gurlek A, Ringkananont U, Weiss RE, Refetoff S. Resistance to thyroid hormone associated with autoimmune thyroid disease in a Turkish family. J Endocrinol Invest. 2005;28(4):379\u201383.","journal-title":"J Endocrinol Invest"},{"issue":"3","key":"3061_CR16","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1507\/endocrj.K05-182","volume":"53","author":"H Sato","year":"2006","unstructured":"Sato H, Sakai H. A family showing resistance to thyroid hormone associated with chronic thyroiditis and its clinical features: a case report. Endocr J. 2006;53(3):421\u20135.","journal-title":"Endocr J"},{"issue":"7","key":"3061_CR17","doi-asserted-by":"publisher","first-page":"3189","DOI":"10.1210\/jc.2009-2179","volume":"95","author":"MS Barkoff","year":"2010","unstructured":"Barkoff MS, Kocherginsky M, Anselmo J, Weiss RE, Refetoff S. Autoimmunity in patients with resistance to thyroid hormone. J Clin Endocrinol Metab. 2010;95(7):3189\u201393.","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"3061_CR18","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1530\/acta.0.1100373","volume":"110","author":"K Kamoi","year":"1985","unstructured":"Kamoi K, Mitsuma T, Sato H, Yokoyama M, Washiyama K, Tanaka R, Arai O, Takasu N, Yamada T. Hyperthyroidism caused by a pituitary thyrotrophin-secreting tumour with excessive secretion of thyrotrophin-releasing hormone and subsequently followed by Graves\u2019 disease in a middle-aged woman. Acta Endocrinol. 1985;110(3):373\u201382.","journal-title":"Acta Endocrinol"},{"issue":"5","key":"3061_CR19","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1530\/eje.0.1510587","volume":"151","author":"N Koriyama","year":"2004","unstructured":"Koriyama N, Nakazaki M, Hashiguchi H, Aso K, Ikeda Y, Kimura T, Eto H, Hirano H, Nakano S, Tei C. Thyrotropin-producing pituitary adenoma associated with Graves\u2019 disease. Eur J Endocrinol. 2004;151(5):587\u201394.","journal-title":"Eur J Endocrinol"},{"issue":"1","key":"3061_CR20","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1159\/000355386","volume":"3","author":"M Kamoun","year":"2014","unstructured":"Kamoun M, d\u2019Herbomez M, Lemaire C, Fayard A, Desailloud R, Huglo D, Wemeau JL. Coexistence of thyroid-stimulating hormone-secreting pituitary adenoma and Graves\u2019 hyperthyroidism. Eur Thyroid J. 2014;3(1):60\u20134.","journal-title":"Eur Thyroid J."}],"container-title":["Journal of Medical Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13256-021-03061-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13256-021-03061-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13256-021-03061-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T23:49:53Z","timestamp":1632527393000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmedicalcasereports.biomedcentral.com\/articles\/10.1186\/s13256-021-03061-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,25]]},"references-count":20,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["3061"],"URL":"https:\/\/doi.org\/10.1186\/s13256-021-03061-4","relation":{},"ISSN":["1752-1947"],"issn-type":[{"value":"1752-1947","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,25]]},"assertion":[{"value":"7 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Although there is no ethical issue in reporting of this case, ethical approval from the Medical Ethics Committee of Toyama Prefectural Central Hospital is provided.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"473"}}