{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:27:42Z","timestamp":1760239662764,"version":"build-2065373602"},"reference-count":23,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Javna Agencija za Raziskovalno Dejavnost RS","doi-asserted-by":"publisher","award":["J3-2356 and P3-0343"],"award-info":[{"award-number":["J3-2356 and P3-0343"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Resistance to thyroid hormone beta (RTH\u03b2) is a syndrome characterized by a reduced response of target tissues to thyroid hormones. In 85% of cases, a pathogenic mutation in the thyroid hormone receptor beta (THRB) gene is found. The clinical picture of RTH\u03b2 is very diverse; the most common findings are goiter and tachycardia, but the patients might be clinically euthyroid. The laboratory findings are almost pathognomonic with elevated free thyroxin (fT4) levels and high or normal thyrotropin (TSH) levels; free triiodothyronin (fT3) levels may also be elevated. We present three siblings with THRB mutation (heterozygous disease-variant c.727C&gt;T, p.Arg243Trp); two of them also had hypercholesterolemia, while all three had several other clinical characteristics of RTH\u03b2. This is the first description of the known Slovenian cases with RTH\u03b2 due to the pathogenic mutation in the THRB gene. Hypercholesterolemia might be etiologically related with RTH\u03b2, since the severity of hormonal resistance varies among different tissues and hypercholesterolemia in patients with THRB variants might indicate the relatively hypothyroid state of the liver. We suggest that cholesterol levels are measured in all RTH\u03b2 patients.<\/jats:p>","DOI":"10.3390\/medicina56120699","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T09:12:57Z","timestamp":1608023577000},"page":"699","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hypercholesterolemia in Two Siblings with Resistance to Thyroid Hormones Due to Disease-Causing Variant in Thyroid Hormone Receptor (THRB) Gene"],"prefix":"10.3390","volume":"56","author":[{"given":"Maja","family":"Pajek","sequence":"first","affiliation":[{"name":"Department of Paediatric Surgery and Intensive Care, University Medical Centre Ljubljana, Bohori\u010deva 20, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0836-5114","authenticated-orcid":false,"given":"Magdalena","family":"Avbelj Stefanija","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolic Diseases, University Children\u2019s Hospital, University Medical Centre Ljubljana, Bohori\u010deva 20, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0154-3547","authenticated-orcid":false,"given":"Katarina","family":"Trebusak Podkrajsek","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolic Diseases, University Children\u2019s Hospital, University Medical Centre Ljubljana, Bohori\u010deva 20, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasna","family":"Suput Omladic","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolic Diseases, University Children\u2019s Hospital, University Medical Centre Ljubljana, Bohori\u010deva 20, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mojca","family":"Zerjav Tansek","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolic Diseases, University Children\u2019s Hospital, University Medical Centre Ljubljana, Bohori\u010deva 20, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadej","family":"Battelino","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolic Diseases, University Children\u2019s Hospital, University Medical Centre Ljubljana, Bohori\u010deva 20, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5246-9869","authenticated-orcid":false,"given":"Urh","family":"Groselj","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolic Diseases, University Children\u2019s Hospital, University Medical Centre Ljubljana, Bohori\u010deva 20, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1023\/A:1010072605757","article-title":"Resistance to Thyroid Hormone","volume":"1","author":"Weiss","year":"2000","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"229","DOI":"10.6065\/apem.2014.19.4.229","article-title":"Resistance to thyroid hormone due to a novel mutation of thyroid hormone receptor beta gene","volume":"19","author":"Lee","year":"2014","journal-title":"Ann. Pediatr. Endocrinol. Metab."},{"key":"ref_3","first-page":"322","article-title":"Thyroid hormone resistance: A novel mutation in thyroid hormone receptor beta (THRB) gene\u2014Case report","volume":"55","author":"Campi","year":"2013","journal-title":"Turk. J. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1159\/000363159","article-title":"Resistance to thyroid hormone","volume":"26","author":"Onigata","year":"2014","journal-title":"Endocr. Dev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/nrendo.2014.143","article-title":"Thyroid hormone receptors and resistance to thyroid hormone disorders","volume":"10","author":"Sidhaye","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1590\/0004-2730000003297","article-title":"A case of thyroid hormone resistance: A rare mutation","volume":"58","author":"Nobre","year":"2014","journal-title":"Arq. Bras. Endocrinol. Metabol."},{"key":"ref_7","first-page":"3609","article-title":"Search for abnormalities of nuclear corepressors, coactivators, and a coregulator in families with resistance to thyroid hormone without mutations in thyroid hormone receptor beta or alpha genes","volume":"85","author":"Reutrakul","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_8","first-page":"4196","article-title":"Dominant inheritance of resistance to thyroid hormone not linked to defects in the thyroid hormone receptor alpha or beta genes may be due to a defective cofactor","volume":"81","author":"Weiss","year":"1996","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"560","DOI":"10.3346\/jkms.2007.22.3.560","article-title":"A newly identified insertion mutation in the thyroid hormone receptor-beta gene in a Korean family with generalized thyroid hormone resistance","volume":"22","author":"Kim","year":"2007","journal-title":"J. Korean Med. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.bbadis.2010.12.019","article-title":"Role of thyroid receptor \u03b2 in lipid metabolism","volume":"1812","author":"Pramfalk","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_11","unstructured":"(2020, October 05). Clinical Variation for Gene Symbols, HGVS Expressions, Condition, and More. NCBI. Last Evaluated 31 May 2018, Available online: http:\/\/www.ncbi.nlm.nih.gov\/clinvar\/variation\/12567\/#clinical-assertions."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1007\/BF03401322","article-title":"Identification of four novel mutations in the thyroid hormone receptor-\u03b2 gene in 164 Spanish and 2 Greek patients with resistance to thyroid hormone","volume":"13","author":"Amor","year":"2014","journal-title":"Hormones"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1507\/endocrj.46.825","article-title":"A de novo L330S point mutation in thyroid hormone receptor beta gene in a Thai female with resistance to thyroid hormone","volume":"46","author":"Ditudompo","year":"1999","journal-title":"Endocr. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.tem.2005.03.008","article-title":"Thyroid hormone receptor mutations and disease: Beyond thyroid hormone resistance","volume":"16","author":"Cheng","year":"2005","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nrendo.2018.10","article-title":"Direct effects of thyroid hormones on hepatic lipid metabolism","volume":"14","author":"Sinha","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1172\/JCI38793","article-title":"Resistance to thyroid hormone is associated with raised energy expenditure, muscle mitochondrial uncoupling, and hyperphagia","volume":"120","author":"Mitchell","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1111\/j.1365-2265.2008.03422.x","article-title":"Augmentation index in resistance to thyroid hormone (RTH)","volume":"70","author":"Owen","year":"2009","journal-title":"Clin. Endocrinol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1016\/j.jacc.2015.07.017","article-title":"Universal screening for familial hypercholesterolemia in children","volume":"66","author":"Bratina","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.atherosclerosis.2018.06.858","article-title":"Universal screening for familial hypercholesterolemia in children: The Slovenian model and literature review","volume":"277","author":"Groselj","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_20","first-page":"767","article-title":"Hypercholesterolemia in children","volume":"2","author":"Shamir","year":"2000","journal-title":"Isr. Med. Assoc. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1515\/jpem-2018-0519","article-title":"Association between mild hyperthyrotropinemia and hypercholesterolemia in children with severe obesity","volume":"32","author":"Iqbal","year":"2019","journal-title":"J. Ped. Endorcinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1530\/EJE-13-0566","article-title":"Decreased prevalence of hypercholesterolaemia and stabilisation of obesity trends in 5-year-old children: Possible effects of changed public health policies","volume":"170","author":"Sedej","year":"2014","journal-title":"Eur. J. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1752-1947-8-12","article-title":"A rare thyroid hormone receptor beta (THR\u03b2) gene mutation in a 15-year-old girl with thyroid hormone resistance syndrome: A case report","volume":"8","author":"Ouhtit","year":"2014","journal-title":"J. Med. Case Rep."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/56\/12\/699\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:45:18Z","timestamp":1760179518000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/56\/12\/699"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,15]]},"references-count":23,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["medicina56120699"],"URL":"https:\/\/doi.org\/10.3390\/medicina56120699","relation":{},"ISSN":["1648-9144"],"issn-type":[{"type":"electronic","value":"1648-9144"}],"subject":[],"published":{"date-parts":[[2020,12,15]]}}}