{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T09:57:45Z","timestamp":1772445465019,"version":"3.50.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF0064985"],"award-info":[{"award-number":["NNF0064985"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Laboratory Endowment Fund at Boston Children\u2019s Hospital"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Brown adipose tissue (BAT) thermogenesis is mediated by sympathetic nervous system activation and enhanced by thyroid hormones via upregulation of uncoupling protein 1. Studying thyroid hormone response to cooling in populations with habitual cold exposure may give new insights to the role of thyroid hormones in non-shivering thermogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Twenty-one participants (11 Greenlanders, 10 Danes) underwent a cross-over protocol with experimental sessions of cooling and thermal comfort, followed by [18F]FDG positron emission tomography\/computed tomography scans. Serial blood samples were collected to assess thyrotropin (TSH), total triiodothyronine (TT3), total thyroxine (TT4), and thyroglobulin (Tg) before, during, and after cooling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cooling induced an increase in TSH (Danes: 0.24 mIU\/L, P &amp;lt; .001; Greenlanders: 0.15 mIU\/L, P = .009). TT3 also increased in response to cooling (Danes: 0.15\u2005nmol\/L, Greenlanders: 0.09\u2005nmol\/L, Pboth &amp;lt; .001). Greenlanders had lower TSH and higher TT3 levels compared to Danes (baseline 0.27\u2005nmol\/L, P = .009) with an attenuated TT3 response to cooling (\u22120.07\u2005nmol\/L, P \u00a0= \u00a0.009). The T3\/T4 ratio was elevated during cold exposure compared to thermoneutral conditions in both Danes (P &amp;lt; .001) and Greenlanders (P = .022), and Greenlanders had consistently higher T3\/T4 ratios compared to Danes (baseline, P = .001; after cooling, P = .023). Finally, Tg levels were higher in participants with low- compared to high-BAT volume (7.27\u2005\u00b5g\/L, P = .008).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Serial measurements of thyroid hormones and thyroglobulin with gold-standard detection of BAT activity documented distinct thyroid responses to cooling. The findings suggested a physiological preparedness to acute cold exposure in individuals with cold adaptation, irrespective of origin.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvag001","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T12:48:18Z","timestamp":1770295698000},"page":"146-156","source":"Crossref","is-referenced-by-count":0,"title":["Thyroid response to cold activation of brown adipose tissue in Greenlanders and Danes"],"prefix":"10.1093","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4129-2218","authenticated-orcid":false,"given":"Mette","family":"Motzfeldt Jensen","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, Aalborg University , Aalborg 9000 ,","place":["Denmark"]},{"name":"Greenland Centre for Health Research, Institute for Health and Nature, Ilisimatusarfik , Nuuk 3900, Greenland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0720-9160","authenticated-orcid":false,"given":"Charlotte Elberling","family":"Almasi","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aalborg University , Aalborg 9000 ,","place":["Denmark"]},{"name":"Department of Nuclear Medicine, Aalborg University Hospital , Aalborg 9000 ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6336-1936","authenticated-orcid":false,"given":"Stine Linding","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aalborg University , Aalborg 9000 ,","place":["Denmark"]},{"name":"Department of Clinical Biochemistry, Aalborg University Hospital , Aalborg 9000 ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3088-4375","authenticated-orcid":false,"given":"Christina","family":"Ellervik","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Zealand University Hospital , K\u00f8ge 4600 ,","place":["Denmark"]},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen 2200 ,","place":["Denmark"]},{"name":"Department of Laboratory Medicine, Boston Children\u2019s Hospital, Harvard Medical School , Boston, MA 02115 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8227-1469","authenticated-orcid":false,"given":"Mette Korre","family":"Andersen","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen , Copenhagen 2200 ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8748-3831","authenticated-orcid":false,"given":"Torben","family":"Hansen","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen , Copenhagen 2200 ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8356-5565","authenticated-orcid":false,"given":"Marit Eika","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Greenland Centre for Health Research, Institute for Health and Nature, Ilisimatusarfik , Nuuk 3900, Greenland"},{"name":"Steno Diabetes Center, Queen Ingrids Hospital , Nuuk 3900, Greenland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3632-5213","authenticated-orcid":false,"given":"Stig","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aalborg University , Aalborg 9000 ,","place":["Denmark"]},{"name":"Greenland Centre for Health Research, Institute for Health and Nature, Ilisimatusarfik , Nuuk 3900, Greenland"},{"name":"Department of Geriatric Medicine, Aalborg University Hospital , Aalborg 9000 ,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"issue":"2","key":"2026030204013580900_lvag001-B1","doi-asserted-by":"publisher","first-page":"R106","DOI":"10.1530\/EC-20-0562","article-title":"Thyroid hormones in the regulation of brown adipose tissue thermogenesis","volume":"10","author":"Sentis","year":"2021","journal-title":"Endocr Connect"},{"issue":"3","key":"2026030204013580900_lvag001-B2","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/S2213-8587(13)70069-X","article-title":"The role of thyroid hormone and brown adipose tissue in energy homoeostasis","volume":"1","author":"Bianco","year":"2013","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"5936","key":"2026030204013580900_lvag001-B3","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1038\/305712a0","article-title":"Adrenergic activation of triiodothyronine production in brown adipose tissue","volume":"305","author":"Silva","year":"1983","journal-title":"Nature"},{"issue":"5","key":"2026030204013580900_lvag001-B4","doi-asserted-by":"publisher","first-page":"E769","DOI":"10.1152\/ajpendo.2000.278.5.E769","article-title":"Triiodothyronine amplifies the adrenergic stimulation of uncoupling protein expression in rat brown adipocytes","volume":"278","author":"Hern\u00e1ndez","year":"2000","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"1","key":"2026030204013580900_lvag001-B5","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1152\/physrev.00015.2003","article-title":"Brown adipose tissue: function and physiological significance","volume":"84","author":"Cannon","year":"2004","journal-title":"Physiol Rev"},{"issue":"1","key":"2026030204013580900_lvag001-B6","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/S0005-2728(00)00247-4","article-title":"UCP1: the only protein able to mediate adaptive non-shivering thermogenesis and metabolic inefficiency","volume":"1504","author":"Nedergaard","year":"2001","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"2026030204013580900_lvag001-B7","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1172\/JCI112798","article-title":"Intracellular conversion of thyroxine to triiodothyronine is required for the optimal thermogenic function of brown adipose tissue","volume":"79","author":"Bianco","year":"1987","journal-title":"J Clin Invest"},{"issue":"3 Pt 1","key":"2026030204013580900_lvag001-B8","doi-asserted-by":"publisher","first-page":"E255","DOI":"10.1152\/ajpendo.1987.253.3.E255","article-title":"Optimal response of key enzymes and uncoupling protein to cold in BAT depends on local T3 generation","volume":"253","author":"Bianco","year":"1987","journal-title":"Am J Physiol"},{"issue":"2","key":"2026030204013580900_lvag001-B9","doi-asserted-by":"publisher","first-page":"E314","DOI":"10.1152\/ajpendo.2000.279.2.E314","article-title":"Evidence of UCP1-independent regulation of norepinephrine-induced thermogenesis in brown fat","volume":"279","author":"Ribeiro","year":"2000","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"4","key":"2026030204013580900_lvag001-B10","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1210\/jcem-70-4-965","article-title":"Changes in serum triiodothyronine (T3) kinetics after prolonged Antarctic residence: the polar T3 syndrome","volume":"70","author":"Reed","year":"1990","journal-title":"J Clin Endocrinol Metab."},{"issue":"3","key":"2026030204013580900_lvag001-B11","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1530\/EJE-11-0888","article-title":"Thyroid hyperactivity with high thyroglobulin in serum despite sufficient iodine intake in chronic cold adaptation in an Arctic inuit hunter population","volume":"166","author":"Andersen","year":"2012","journal-title":"Eur J Endocrinol"},{"issue":"6254","key":"2026030204013580900_lvag001-B12","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1126\/science.aab2319","article-title":"Greenlandic inuit show genetic signatures of diet and climate adaptation","volume":"349","author":"Fumagalli","year":"2015","journal-title":"Science"},{"issue":"1","key":"2026030204013580900_lvag001-B13","doi-asserted-by":"publisher","first-page":"2545662","DOI":"10.1080\/22423982.2025.2545662","article-title":"Cross-over comparative study of cold-induced brown adipose tissue activity in Greenlandic inuit and Danes: rationale, design, and methodology","volume":"84","author":"Motzfeldt Jensen","year":"2025","journal-title":"Int J Circumpolar Health"},{"issue":"146","key":"2026030204013580900_lvag001-B14","doi-asserted-by":"publisher","first-page":"e58469","DOI":"10.3791\/58469","article-title":"Whole body and regional quantification of active human brown adipose tissue using 18F-FDG PET\/CT","volume":"2019","author":"Kim","year":"2019","journal-title":"J Vis Exp"},{"issue":"8","key":"2026030204013580900_lvag001-B15","doi-asserted-by":"publisher","first-page":"3020","DOI":"10.3390\/ijms21083020","article-title":"Thermogenesis in adipose tissue activated by thyroid hormone","volume":"21","author":"Yau","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"5 Pt 1","key":"2026030204013580900_lvag001-B16","doi-asserted-by":"publisher","first-page":"E786","DOI":"10.1152\/ajpendo.1994.266.5.E786","article-title":"Changes in serum triiodothyronine kinetics and hepatic type I 5'-deiodinase activity of cold-exposed swine","volume":"266","author":"Reed","year":"1994","journal-title":"Am J Physiol"},{"issue":"4","key":"2026030204013580900_lvag001-B17","doi-asserted-by":"publisher","first-page":"2149","DOI":"10.1210\/endo-128-4-2149","article-title":"Central role of brown adipose tissue thyroxine 5\u2032-deiodinase on thyroid hormone-dependent thermogenic response to cold","volume":"128","author":"Carvalho","year":"1991","journal-title":"Endocrinology"},{"issue":"9","key":"2026030204013580900_lvag001-B18","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1172\/JCI200113803","article-title":"The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue","volume":"108","author":"de Jesus","year":"2001","journal-title":"J Clin Invest"},{"issue":"2","key":"2026030204013580900_lvag001-B19","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1089\/thy.2007.0254","article-title":"Thyroid hormone and adipocyte differentiation","volume":"18","author":"Obregon","year":"2008","journal-title":"Thyroid"},{"issue":"2","key":"2026030204013580900_lvag001-B20","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1530\/JOE-16-0425","article-title":"Thyroid hormones induce browning of white fat","volume":"232","author":"Mart\u00ednez-S\u00e1nchez","year":"2017","journal-title":"J Endocrinol"},{"issue":"10","key":"2026030204013580900_lvag001-B21","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1038\/nm.3361","article-title":"Brown and beige fat: development, function and therapeutic potential","volume":"19","author":"Harms","year":"2013","journal-title":"Nat Med"},{"issue":"9","key":"2026030204013580900_lvag001-B22","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1038\/nm.2207","article-title":"Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance","volume":"16","author":"L\u00f3pez","year":"2010","journal-title":"Nat Med"},{"issue":"4","key":"2026030204013580900_lvag001-B23","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1210\/jcem-39-4-713","article-title":"Sympathetic innervation of the normal human thyroid","volume":"39","author":"Melander","year":"1974","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2026030204013580900_lvag001-B24","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1210\/endo-96-1-102","article-title":"Sympathetic innervation of the thyroid: variation with species and with age","volume":"96","author":"Melander","year":"1975","journal-title":"Endocrinology"},{"issue":"1","key":"2026030204013580900_lvag001-B25","doi-asserted-by":"publisher","first-page":"e240272","DOI":"10.1530\/ETJ-24-0272","article-title":"Thyroid response to blocking sympathetic activity in chronic cold exposed hunters in East Greenland: a case-control study","volume":"14","author":"Motzfeldt Jensen","year":"2024","journal-title":"Eur Thyroid J"},{"issue":"1","key":"2026030204013580900_lvag001-B26","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1038\/s41572-020-0184-y","article-title":"Graves' disease","volume":"6","author":"Davies","year":"2020","journal-title":"Nat Rev Dis Primers"},{"issue":"6","key":"2026030204013580900_lvag001-B27","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1159\/000493976","article-title":"TRH neurons and thyroid hormone coordinate the hypothalamic response to cold","volume":"7","author":"Zhang","year":"2018","journal-title":"Eur Thyroid J"},{"issue":"10","key":"2026030204013580900_lvag001-B28","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1038\/s41574-019-0237-z","article-title":"Interconnection between circadian clocks and thyroid function","volume":"15","author":"Ikegami","year":"2019","journal-title":"Nat Rev Endocrinol"},{"issue":"11","key":"2026030204013580900_lvag001-B29","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1089\/105072503770867237","article-title":"Biologic variation is important for interpretation of thyroid function tests","volume":"13","author":"Andersen","year":"2003","journal-title":"Thyroid"},{"issue":"1","key":"2026030204013580900_lvag001-B30","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.ajhg.2014.11.012","article-title":"Uncovering the genetic history of the present-day Greenlandic population","volume":"96","author":"Moltke","year":"2015","journal-title":"Am J Hum Genet"},{"issue":"8054","key":"2026030204013580900_lvag001-B31","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1038\/s41586-024-08516-4","article-title":"Genetic architecture in Greenland is shaped by demography, structure and selection","volume":"639","author":"St\u00e6ger","year":"2025","journal-title":"Nature"},{"issue":"1","key":"2026030204013580900_lvag001-B32","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1017\/S0007114512004709","article-title":"Vitamin D status in North Greenland is influenced by diet and season: indicators of dermal 25-hydroxy vitamin D production north of the Arctic circle","volume":"110","author":"Andersen","year":"2013","journal-title":"Br J Nutr"},{"issue":"7","key":"2026030204013580900_lvag001-B33","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.2337\/db10-0004","article-title":"Impact of age on the relationships of brown adipose tissue with sex and adiposity in humans","volume":"59","author":"Pfannenberg","year":"2010","journal-title":"Diabetes"},{"issue":"1","key":"2026030204013580900_lvag001-B34","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1210\/jc.2010-0989","article-title":"Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans","volume":"96","author":"Ouellet","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"issue":"13-14","key":"2026030204013580900_lvag001-B35","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1016\/j.clinbiochem.2014.06.007","article-title":"Total and free thyroxine and triiodothyronine: measurement discrepancies, particularly in inpatients","volume":"47","author":"Jonklaas","year":"2014","journal-title":"Clin Biochem"},{"issue":"3","key":"2026030204013580900_lvag001-B36","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1080\/07420528.2020.1865394","article-title":"Seasonal variations in levels of human thyroid-stimulating hormone and thyroid hormones: a meta-analysis","volume":"38","author":"Kuzmenko","year":"2021","journal-title":"Chronobiol Int"}],"container-title":["European Journal of Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ejendo\/article-pdf\/194\/2\/146\/66840698\/lvag001.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejendo\/article-pdf\/194\/2\/146\/66840698\/lvag001.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T09:01:41Z","timestamp":1772442101000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/194\/2\/146\/8471271"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2,4]]}},"URL":"https:\/\/doi.org\/10.1093\/ejendo\/lvag001","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,2]]},"published":{"date-parts":[[2026,2]]}}}