{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T01:17:24Z","timestamp":1773278244630,"version":"3.50.1"},"reference-count":25,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2020,4,18]],"date-time":"2020-04-18T00:00:00Z","timestamp":1587168000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Longevity is associated with higher circulating levels of TSH in the absence of differences in circulating thyroid hormones (TH), as previously observed in F2 members of long-lived families (F2-LLS) and their partners (F2-Con). The mechanism underlying this observed difference remains unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We hypothesized that the thyroid gland of members from long-lived families are less responsive to TSH stimulation, thereby requiring higher circulating TSH levels to maintain adequate TH levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed a case-control intervention study with a single intramuscular (gluteal) injection with 0.1 mg recombinant human TSH in a subgroup of 14 F2-LLS and 15 similarly aged F2-Con. They were followed for 4 days. No serious adverse events were reported. For analyses, we compared time trajectories of TSH and TH, and the ratio of TH to TSH using area under the curve (AUC) calculations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The AUC free T4\/AUC TSH ratio was significantly lower in F2-LLS than in F2-Con (estimated mean [95% confidence interval] 1.6 [1.2-1.9] and 2.2 [1.9-2.6], respectively, P = 0.01). The AUC thyroglobulin\/AUC TSH ratio was also lower in F2-LLS than in F2-Con (median [interquartile range] 2.1 [1.4-3.6] and 3.2 [2.7-7.4], respectively, P = 0.04). We observed the same trend with the AUC free T3\/AUC TSH ratio, although the difference was not statistically significant (estimated mean [95% confidence interval] 0.6 [0.4-0.7] and 0.7 [0.6-0.8], respectively, P = 0.07).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The present findings show that members of long-living families have a lower thyroid responsivity to TSH compared with their partners.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa195","type":"journal-article","created":{"date-parts":[[2020,4,18]],"date-time":"2020-04-18T02:15:39Z","timestamp":1587176139000},"page":"e2572-e2580","source":"Crossref","is-referenced-by-count":10,"title":["Familial Longevity is Associated with an Attenuated Thyroidal Response to Recombinant Human Thyroid Stimulating Hormone"],"prefix":"10.1210","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9224-7179","authenticated-orcid":false,"given":"Ana","family":"Zutinic","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Divis ion of Gerontology and Geriatrics, Leiden University Medical Centre, ZA, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3076-1551","authenticated-orcid":false,"given":"Hanno","family":"Pijl","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology and Metabolic Diseases, Leiden University Medical Centre, ZA, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart E","family":"Ballieux","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Centre, ZA, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6276-2834","authenticated-orcid":false,"given":"Ferdinand","family":"Roelfsema","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology and Metabolic Diseases, Leiden University Medical Centre, ZA, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudi G J","family":"Westendorp","sequence":"additional","affiliation":[{"name":"Public Health and Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard J","family":"Blauw","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Divis ion of Gerontology and Geriatrics, Leiden University Medical Centre, ZA, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"van Heemst","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Divis ion of Gerontology and Geriatrics, Leiden University Medical Centre, ZA, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2020,4,18]]},"reference":[{"issue":"4","key":"2020073114170515500_CIT0001","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1210\/er.2012-1056","article-title":"Thyroid hormone signaling and homeostasis during aging","volume":"34","author":"Bowers","year":"2013","journal-title":"Endocr Rev."},{"issue":"4","key":"2020073114170515500_CIT0002","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1210\/jc.2008-2325","article-title":"Extreme longevity is associated with increased serum thyrotropin","volume":"94","author":"Atzmon","year":"2009","journal-title":"J Clin Endocrinol 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