{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:55:27Z","timestamp":1792029327122,"version":"4.4.0"},"reference-count":10,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T00:00:00Z","timestamp":1680566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Resistance to thyroid hormone (RTH) is a syndrome characterized by impaired responsiveness of target tissues to thyroid hormones. The relationship between RTH<jats:italic>\u03b2<\/jats:italic> and thyroid autoimmunity has been under research. In this study, we demonstrate a case report of a woman with a novel mutation in <jats:italic>THR\u03b2<\/jats:italic> gene coexisting with autoimmune thyroid disease (AITD). The 36-year-old woman has been treated since childhood for a thyroid disease. Based on high levels of thyroid hormones (THs) and elevated concentrations of thyroperoxidase and thyroglobulin antibodies (TPOAb and TgAb, respectively), she received unnecessary long-term treatment with methimazole and finally underwent subtotal thyroidectomy. After the surgery, her TSH level remained significantly elevated, despite the treatment with 150 + 15\u00a0\u00b5g of thyroxine and triiodothyronine. A sequence analysis of the <jats:italic>THR\u03b2<\/jats:italic> gene revealed a novel dinucleotide substitution affecting codon 453, resulting in the replacement of the normal proline with an asparagine (c.1357_1358delinsAA, p.(Pro453Asn)). The mutation has not been described in the literature yet; however, <jats:italic>THR\u03b2<\/jats:italic> codon 453 represents a mutational hot spot, frequently altered in the TH receptor \u00df gene. After establishing the diagnosis of RTH, the patient was treated with 300\u00a0\u00b5g of thyroxine, which showed clinical improvement and normalization of TSH. The coexistence of RTH<jats:italic>\u03b2<\/jats:italic> and AITD may additionally impede establishment of a proper diagnosis, leading to unnecessary therapy and delayed correct treatment. The presented case encourages a closer cooperation between clinical endocrinologists and geneticists.<\/jats:p>","DOI":"10.3389\/fgene.2023.1051042","type":"journal-article","created":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T09:52:27Z","timestamp":1680601947000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Resistance to thyroid hormone due to a novel mutation in the thyroid beta receptor (THR\u03b2) gene coexisting with autoimmune thyroid disease\u2014A case report"],"prefix":"10.3389","volume":"14","author":[{"given":"El\u017cbieta","family":"Skowro\u0144ska-J\u00f3\u017awiak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Gach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Cyniak-Magierska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Nykel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Jurkowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Lewi\u0144ski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3189","DOI":"10.1210\/jc.2009-2179","article-title":"Autoimmunity in patients with resistance to thyroid hormone","volume":"95","author":"Barkoff","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B2","doi-asserted-by":"publisher","first-page":"3987","DOI":"10.1016\/j.bbagen.2012.08.005","article-title":"The syndromes of reduced sensitivity to thyroid hormone","volume":"1830","author":"Dumitrescu","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1016\/j.mehy.2007.08.015","article-title":"Proposing a causal link between thyroid hormone resistance and primary autoimmune hypothyroidism","volume":"70","author":"Gavin","year":"2008","journal-title":"Med. Hypotheses"},{"key":"B4","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/BF03350495","article-title":"Elevated serum thyroxine concentration in patients receiving \u201creplacement\u201d doses of levothyroxine","volume":"5","author":"Ingbar","year":"1982","journal-title":"J. Endocrinol. Invest."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.1089\/thy.2013.0174","article-title":"Incidental identification of a thyroid hormone receptor beta (THRB) gene variant in a family with autoimmune thyroid disease","volume":"23","author":"Larsen","year":"2013","journal-title":"Thyroid"},{"key":"B6","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1258\/000456306778904678","article-title":"Thyroid hormone resistance","volume":"43","author":"Olateju","year":"2006","journal-title":"Ann. Clin. Biochem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"656551","DOI":"10.3389\/fendo.2021.656551","article-title":"Resistance to thyroid hormone beta: A focused review","volume":"12","author":"Pappa","year":"2021","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"B8","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1210\/er.2002-0030","article-title":"Searching for the autoimmune thyroid disease susceptibility genes: From gene mapping to gene function","volume":"24","author":"Tomer","year":"2003","journal-title":"Endocr. Rev."},{"key":"B9","doi-asserted-by":"publisher","first-page":"288","DOI":"10.4158\/EP.12.3.288","article-title":"Difficulties in diagnosing and managing coexisting primary hypothyroidism and resistance to thyroid hormone","volume":"12","author":"Tran","year":"2006","journal-title":"Endocr. Pract."},{"key":"B10","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1186\/s12884-018-2110-9","article-title":"Resistance to thyroid hormone \u03b2 in autoimmune thyroid disease: A case report and review of literature","volume":"18","author":"Wu","year":"2018","journal-title":"BMC Pregnancy Childbirth"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1051042\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T09:52:28Z","timestamp":1680601948000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1051042\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,4]]},"references-count":10,"alternative-id":["10.3389\/fgene.2023.1051042"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2023.1051042","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,4]]},"article-number":"1051042"}}