{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:45:16Z","timestamp":1792010716966,"version":"4.4.0"},"reference-count":36,"publisher":"The Endocrine Society","issue":"5","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["210755\/Z\/18\/Z to\u00a0KC"],"award-info":[{"award-number":["210755\/Z\/18\/Z to\u00a0KC"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["219496\/Z\/19\/Z"],"award-info":[{"award-number":["219496\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIHR Cambridge Biomedical Research Centre"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>In resistance to thyroid hormone due to mutations in thyroid hormone receptor \u03b2, peripheral tissues are variably refractory to the action of circulating thyroid hormones. We evaluated parameters contributing to atherosclerotic risk in this disorder.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We measured low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), nonesterified fatty acids (NEFA), intrahepatic lipid (IHL) and intramyocellular lipid (IMCL), Homeostasis-model assessment of insulin resistance (HOMA-IR), augmentation index (AIx) and pulse wave velocity (PWV), flow-mediated dilatation, and carotid intima-media thickness (cIMT) in an unselected, genetically confirmed cohort of adult RTH\u03b2 patients (n\u2005=\u200527-77) and compared these with measurements in healthy subjects (up to n\u2005=\u2005100) and thyrotoxic patients (n\u2005=\u200540).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Resistance to thyroid hormone beta (RTH\u03b2) patients exhibited higher LDL-C (P\u2005=\u20050.008) and TG (P\u2005=\u20050.002) and lower HDL-C concentrations (P\u2005=\u20050.015\u2005\u00d7\u200510\u20132) than control subjects, with LDL-C being higher than in thyrotoxic patients with comparable hyperthyroxinemia. Proprotein convertase subtilisin\/kexin 9 (P\u2005=\u20050.002) and apolipoprotein B (P\u2005=\u20050.0009) levels were reduced in thyrotoxic patients but not lower in RTH\u03b2 patients or control subjects. Intrahepatic lipid (P\u2005=\u20050.02\u2005\u00d7\u200510\u20134), IMCL (P\u2005=\u20050.002), HOMA-IR (P\u2005=\u20050.01\u2005\u00d7\u200510\u20132), and NEFA (P\u2005=\u20050.04\u2005\u00d7\u200510\u20136) were significantly higher in RTH\u03b2 patients than control subjects. Flow-mediated dilatation was increased (P\u2005=\u20050.04) but cIMT (P\u2005=\u20050.71), PWV P\u2005=\u20050.81), and AIx (P\u2005=\u20050.95) were unaltered in RTH\u03b2 patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We have documented mixed dyslipidemia with hepatic and IMCL accumulation in RTH\u03b2, suggesting that surveillance for these metabolic abnormalities is warranted. How they combine with enhanced endothelial function and unaltered vessel wall thickness and compliance to determine overall cardiometabolic risk in this disorder remains to be defined.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgab002","type":"journal-article","created":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T23:58:41Z","timestamp":1612310321000},"page":"e2005-e2014","source":"Crossref","is-referenced-by-count":34,"title":["Dyslipidemia, Insulin Resistance, Ectopic Lipid Accumulation, and Vascular Function in Resistance to Thyroid Hormone \u03b2"],"prefix":"10.1210","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7318-7166","authenticated-orcid":false,"given":"Carla","family":"Moran","sequence":"first","affiliation":[{"name":"Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmel M","family":"McEniery","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Schoenmakers","sequence":"additional","affiliation":[{"name":"Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Hillingdon Hospital, Hillingdon, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Sleigh","sequence":"additional","affiliation":[{"name":"Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK"},{"name":"Wolfson Brain Imaging Centre, University of Cambridge School of Clinical Medicine, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Watson","sequence":"additional","affiliation":[{"name":"Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta","family":"Lyons","sequence":"additional","affiliation":[{"name":"Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Burling","sequence":"additional","affiliation":[{"name":"NIHR Cambridge BRC Core Biochemical Assay Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Barker","sequence":"additional","affiliation":[{"name":"NIHR Cambridge BRC Core Biochemical Assay Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2021,2,1]]},"reference":[{"issue":"8","key":"2021122204521050800_CIT0001","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1089\/thy.2019.0763","article-title":"A direct comparison of thyroid hormone receptor protein levels in mice provides unexpected insights into thyroid hormone action","volume":"30","author":"Minakhina","year":"2020","journal-title":"Thyroid."},{"issue":"7","key":"2021122204521050800_CIT0002","doi-asserted-by":"crossref","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":"2021122204521050800_CIT0003","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1172\/JCI115225","article-title":"Thyroid hormone resistance syndrome: inhibition of normal receptor function by mutant thyroid hormone receptor","volume":"87","author":"Chatterjee","year":"1991","journal-title":"J Clin Invest."},{"issue":"11","key":"2021122204521050800_CIT0004","doi-asserted-by":"crossref","first-page":"3246","DOI":"10.1210\/jcem.80.11.7593433","article-title":"Do clinical manifestations of resistance to thyroid hormone correlate with the functional alteration of the corresponding mutant thyroid hormone-beta receptors?","volume":"80","author":"Hayashi","year":"1995","journal-title":"J Clin Endocrinol Metab."},{"issue":"4","key":"2021122204521050800_CIT0005","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 Invest"},{"issue":"1","key":"2021122204521050800_CIT0006","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1210\/jcem.87.1.8170","article-title":"Cardiac involvement in thyroid hormone resistance","volume":"87","author":"Kahaly","year":"2002","journal-title":"J Clin Endocrinol Metab."},{"issue":"1","key":"2021122204521050800_CIT0007","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1210\/jcem-71-1-19","article-title":"Sex hormone binding globulin measurement in patients with inappropriate secretion of thyrotropin (IST): evidence against selective pituitary thyroid hormone resistance in non-neoplastic IST","volume":"71","author":"Beck-Peccoz","year":"1990","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2021122204521050800_CIT0008","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1530\/EJE-15-1249","article-title":"The hypercoagulable state in hyperthyroidism is mediated via the thyroid hormone b receptor pathway","volume":"174","author":"Elbers","year":"2016","journal-title":"Eur J Endocrinol."},{"issue":"1","key":"2021122204521050800_CIT0009","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1210\/jcem-66-1-51","article-title":"Lipoproteins, lipolytic enzymes and hormonal status in hypothyroid women at different levels of substitution","volume":"66","author":"Kuusi","year":"1988","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2021122204521050800_CIT0010","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.arcmed.2004.08.003","article-title":"Plasma CRP, apolipoprotein A-1, apolipoprotein B and Lpa levels according to thyroid function status","volume":"35","author":"Lee","year":"2004","journal-title":"Arch Med Res."},{"issue":"8","key":"2021122204521050800_CIT0011","doi-asserted-by":"crossref","first-page":"3204","DOI":"10.1210\/jc.2016-1300","article-title":"Thyroid function and the risk of non-alcoholic fatty liver disease: the Rotterdam study","volume":"101","author":"Bano","year":"2016","journal-title":"J Clin Endocrinol Metab."},{"issue":"10","key":"2021122204521050800_CIT0012","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1089\/thy.2018.0257","article-title":"Association between primary hypothyroidism and nonalcoholic fatty liver disease: a systematic review and meta-analysis","volume":"28","author":"Mantovani","year":"2018","journal-title":"Thyroid."},{"issue":"6","key":"2021122204521050800_CIT0013","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1089\/thy.2007.0051","article-title":"Thyroid disease and vascular function","volume":"17","author":"Owen","year":"2007","journal-title":"Thyroid."},{"issue":"5","key":"2021122204521050800_CIT0014","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1046\/j.1365-2265.2003.01893.x","article-title":"Decrease in carotid intima-media thickness in hypothyroid patients after normalization of thyroid function","volume":"59","author":"Nagasaki","year":"2003","journal-title":"Clin Endocrinol (Oxf)."},{"issue":"6","key":"2021122204521050800_CIT0015","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1210\/jc.2003-030398","article-title":"Hypothyroidism and atherosclerosis","volume":"88","author":"Cappola","year":"2003","journal-title":"J Clin Endocrinol Metab."},{"key":"2021122204521050800_CIT0016"},{"issue":"2","key":"2021122204521050800_CIT0017","first-page":"315","article-title":"Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis","volume":"119","author":"Semple","year":"2009","journal-title":"J Clin Invest."},{"issue":"6","key":"2021122204521050800_CIT0018","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1210\/jc.2013-4542","article-title":"Low circulating levels of IGF-1 in healthy adults are associated with reduced \u03b2-cell function, increased intramyocellular lipid and enhanced fat utilization during fasting","volume":"99","author":"Thankamony","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"2021122204521050800_CIT0019","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1161\/HYPERTENSIONAHA.107.089391","article-title":"Isolated systolic hypertension is characterized by increased aortic stiffness and endothelial dysfunction","volume":"50","author":"Wallace","year":"2007","journal-title":"Hypertension."},{"key":"2021122204521050800_CIT0020","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1475-2840-10-3","article-title":"Relationship between intima-media thickness of the common carotid artery and arterial stiffness in subjects with and without type 2 diabetes: a case-series report","volume":"10","author":"G\u00f3mez-Marcos","year":"2011","journal-title":"Cardiovasc Diabetol."},{"issue":"12 Pt 2","key":"2021122204521050800_CIT0021","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1097\/00004872-199816121-00033","article-title":"Reproducibility of pulse wave velocity and augmentation index measured by pulse wave analysis","volume":"16","author":"Wilkinson","year":"1998","journal-title":"J Hypertens."},{"issue":"3","key":"2021122204521050800_CIT0022","first-page":"348","article-title":"The syndromes of resistance to thyroid hormone","volume":"14","author":"Refetoff","year":"1993","journal-title":"Endocr Rev."},{"issue":"11","key":"2021122204521050800_CIT0023","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.1194\/jlr.M051664","article-title":"Thyroid hormone reduces PCSK9 and stimulates bile acid synthesis in humans","volume":"55","author":"Bonde","year":"2014","journal-title":"J Lipid Res."},{"key":"2021122204521050800_CIT0024","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/joim.12261","article-title":"Reductions in serum levels of LDL cholesterol, apolipoprotein B, triglycerides and lipoprotein (a) in hypercholesterolaemic patients treated with the liver-selective thyroid hormone receptor agonist eprotirome","volume":"277","author":"Angelin","year":"2015","journal-title":"J Intern Med"},{"issue":"8","key":"2021122204521050800_CIT0025","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1089\/thy.2009.0212","article-title":"Decreased lipid intermediate levels and lipid oxidation rates despite normal lipolysis in patients with hypothyroidism","volume":"20","author":"Gjedde","year":"2010","journal-title":"Thyroid."},{"issue":"6","key":"2021122204521050800_CIT0026","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1089\/thy.2011.0279","article-title":"Inverse association between serum free thyroxine levels and hepatic steatosis: results from the Study of Health in Pomerania","volume":"22","author":"Ittermann","year":"2012","journal-title":"Thyroid."},{"issue":"9","key":"2021122204521050800_CIT0027","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.1210\/jc.2009-0212","article-title":"Thyroid hormone-related regulation of gene expression in human fatty liver","volume":"94","author":"Pihlajam\u00e4ki","year":"2009","journal-title":"J Clin Endocrinol Metab."},{"issue":"3","key":"2021122204521050800_CIT0028","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1210\/me.2008-0311","article-title":"Distinct dysregulation of lipid metabolism by unliganded thyroid hormone receptor isoforms","volume":"23","author":"Araki","year":"2009","journal-title":"Mol Endocrinol."},{"issue":"1","key":"2021122204521050800_CIT0029","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1172\/JCI114961","article-title":"Functional relationship of thyroid hormone-induced lipogenesis, lipolysis, and thermogenesis in the rat","volume":"87","author":"Oppenheimer","year":"1991","journal-title":"J Clin Invest."},{"key":"2021122204521050800_CIT0030","first-page":"1","article-title":"Role of intramyocellular lipids in human health","volume":"809","author":"Coen","year":"2012","journal-title":"Trends Endocrinol Metabol"},{"issue":"1","key":"2021122204521050800_CIT0031","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1161\/ATVBAHA.107.147538","article-title":"Fatty liver: a novel component of the metabolic syndrome","volume":"28","author":"Kotronen","year":"2008","journal-title":"Arterioscler Thromb Vasc Biol."},{"issue":"4","key":"2021122204521050800_CIT0032","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 (Oxf)."},{"issue":"25","key":"2021122204521050800_CIT0033","doi-asserted-by":"crossref","first-page":"3076","DOI":"10.1161\/hc5001.100621","article-title":"Impact of hyperthyroidism and its correction on vascular reactivity in humans","volume":"104","author":"Napoli","year":"2001","journal-title":"Circulation."},{"issue":"38","key":"2021122204521050800_CIT0034","doi-asserted-by":"crossref","first-page":"14104","DOI":"10.1073\/pnas.0601600103","article-title":"Rapid nongenomic actions of thyroid hormone","volume":"103","author":"Hiroi","year":"2006","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"2","key":"2021122204521050800_CIT0035","doi-asserted-by":"crossref","first-page":"e77","DOI":"10.1016\/j.atherosclerosis.2008.09.022","article-title":"Thyroid function is associated with carotid intima-media thickness in euthyroid subjects","volume":"204","author":"Takamura","year":"2009","journal-title":"Atherosclerosis."},{"issue":"10213","key":"2021122204521050800_CIT0036","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1016\/S0140-6736(19)32517-6","article-title":"Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial","volume":"394","author":"Harrison","year":"2019","journal-title":"Lancet."}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgab002\/36166785\/dgab002.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/106\/5\/e2005\/41848361\/dgab002.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/106\/5\/e2005\/41848361\/dgab002.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T04:53:43Z","timestamp":1640148823000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/106\/5\/e2005\/6125725"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,1]]},"references-count":36,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,2,1]]},"published-print":{"date-parts":[[2021,4,23]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgab002","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,5,1]]},"published":{"date-parts":[[2021,2,1]]}}}