{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:09:53Z","timestamp":1783487393158,"version":"3.55.0"},"reference-count":53,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T00:00:00Z","timestamp":1409529600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      3,5-Diiodo-L-thyronine (3,5-T\n                      <jats:sub>2<\/jats:sub>\n                      ), a potential metabolite of 3,3\u2032,5-triiodothyronine (T\n                      <jats:sub>3<\/jats:sub>\n                      ), exerts marked metabolic actions without the undesirable cardiac and central side effects of T\n                      <jats:sub>3<\/jats:sub>\n                      . So far the lack of reliable quantification methods for endogenous 3,5-T\n                      <jats:sub>2<\/jats:sub>\n                      in human serum has limited further insight into its physiological and pathophysiological roles in endocrine homeostasis and disease status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Monoclonal anti-3,5-T\n                      <jats:sub>2<\/jats:sub>\n                      antibodies (3,5-T\n                      <jats:sub>2<\/jats:sub>\n                      mAbs) were produced in mice. We developed a competitive chemiluminescence immunoassay (CLIA) with one selected mAb and optimized it for high sensitivity, linearity, recovery, and low cross-reactivity to structurally related thyroid hormones (THs) and thyronamines. The CLIA was then used to investigate the origin and action of 3,5-T\n                      <jats:sub>2<\/jats:sub>\n                      in humans under physiological and pathophysiological conditions in comparison with THs. Patient analysis included individuals with confirmed hypo- or hyperthyroidism and a separate population of thyroidectomized patients on L-thyroxine (T\n                      <jats:sub>4<\/jats:sub>\n                      ) replacement therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      3,5-T\n                      <jats:sub>2<\/jats:sub>\n                      is stable in human serum after storage at 4\u00b0C or room temperature as well as several freeze\u2013thaw cycles. The immunoassay did not show any significant cross-reactivity with naturally occurring TH metabolites in physiological and pathophysiological concentrations. The assay shows a lower detection limit of 0.2\u2009nM 3,5-T\n                      <jats:sub>2<\/jats:sub>\n                      and an upper detection limit of 10.0\u2009nM. The newly established CLIA generates reliable results after spiking exogenous 3,5-T\n                      <jats:sub>2<\/jats:sub>\n                      or by linear dilution of sera. Intra-assay variation is between 4.1% and 9.0%. Overall mean of variation between different assays is 5.6%\u201312.9%. 3,5-T\n                      <jats:sub>2<\/jats:sub>\n                      serum concentrations do not differ in hyperthyroid (0.31\u00b10.02\u2009nM,\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =24) compared to hypothyroid (0.43\u00b10.04\u2009nM,\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =31) individuals. 3,5-T\n                      <jats:sub>2<\/jats:sub>\n                      was detectable and elevated in serum from thyroidectomized and T\n                      <jats:sub>4<\/jats:sub>\n                      -substituted patients (0.48\u00b10.03\u2009nM,\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =100) in comparison to a sex- and age-matched control group (0.29\u00b10.01\u2009nM,\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =99).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      The established CLIA is highly specific, sensitive, precise and accurate for 3,5-T\n                      <jats:sub>2<\/jats:sub>\n                      detection in human serum. Because 3,5-T\n                      <jats:sub>2<\/jats:sub>\n                      is not regulated in conditions of an altered thyroid state, it is most likely that serum 3,5-T\n                      <jats:sub>2<\/jats:sub>\n                      concentrations are not directly dependent on feedback regulation via the hypothalamic\u2013pituitary axis. In addition 3,5-T\n                      <jats:sub>2<\/jats:sub>\n                      is present in thyroidectomized individuals on T\n                      <jats:sub>4<\/jats:sub>\n                      substitution, and it is elevated after T\n                      <jats:sub>4<\/jats:sub>\n                      substitution compared with healthy controls. We conclude that these data support extrathyroidal production of 3,5-T\n                      <jats:sub>2<\/jats:sub>\n                      from T\n                      <jats:sub>4<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2013.0688","type":"journal-article","created":{"date-parts":[[2014,6,26]],"date-time":"2014-06-26T17:15:44Z","timestamp":1403802944000},"page":"1350-1360","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":51,"title":["Detection of 3,5-Diiodothyronine in Sera of Patients with Altered Thyroid Status Using a New Monoclonal Antibody-Based Chemiluminescence Immunoassay"],"prefix":"10.1177","volume":"24","author":[{"given":"Ina","family":"Lehmphul","sequence":"first","affiliation":[{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Brabant","sequence":"additional","affiliation":[{"name":"University of L\u00fcbeck","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri","family":"Wallaschofski","sequence":"additional","affiliation":[{"name":"University Medicine Greifswald","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Ruchala","sequence":"additional","affiliation":[{"name":"University of Medical Sciences","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian J.","family":"Strasburger","sequence":"additional","affiliation":[{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"K\u00f6hrle","sequence":"additional","affiliation":[{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zida","family":"Wu","sequence":"additional","affiliation":[{"name":"Charit\u00e9-Universit\u00e4tsmedizin Berlin","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,9,1]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2007.0248"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0b013e32833cf354"},{"key":"e_1_3_3_4_2","first-page":"655","article-title":"3,5-Diiodo-L-thyronine increases resting metabolic rate and reduces body weight without undesirable side effects","volume":"25","author":"Antonelli A","year":"2011","unstructured":"Antonelli A, , Fallahi P, , Ferrari SM, , Di Domenicantonio A, , Moreno M, , Lanni A, , Goglia F. 2011. 3,5-Diiodo-L-thyronine increases resting metabolic rate and reduces body weight without undesirable side effects. J Biol Regul Homeost Agents, 25:655\u2013660.","journal-title":"J Biol Regul Homeost Agents"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2007.04.004"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1450291"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.138.8.5333"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0190137"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2009.10.009"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2013-1030"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-3977fje"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90642.2008"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-181982"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.2337\/db11-0207"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.03.023"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1039\/c0mb00040j"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-11-0288"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.141.5.7449"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0345"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.09.027"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2610945"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(92)90138-V"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1042\/bst020059s"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1360059"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(94)90150-3"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0130275"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.1998.2520325.x"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)00229-X"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2728(03)00027-6"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2003.06.005"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-011-9366-3"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.143.5.8767"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.90604.2007"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00389.2011"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-49-3-399"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-55-1-8"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.143.2.8613"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.3732"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1978.tb02187.x"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-50-6-1075"},{"key":"e_1_3_3_41_2","first-page":"196","article-title":"A radioimmunoassay of serum 3,5-diiodothyronine","volume":"97","author":"Kirkegaard C","year":"1981","unstructured":"Kirkegaard C, , Faber J, , Siersbaek-Nielsen K, , Friis T. 1981. A radioimmunoassay of serum 3,5-diiodothyronine. Acta Endocrinol, 97:196\u2013201.","journal-title":"Acta Endocrinol"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-52-3-517"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-58-1-49"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.82.5.3939"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/jms.971"},{"key":"e_1_3_3_46_2","first-page":"2613","article-title":"Immunofunctional assay of human growth hormone (hGH) in serum: a possible consensus for quantitative hGH measurement","volume":"81","author":"Strasburger CJ","year":"1996","unstructured":"Strasburger CJ, , Wu Z, , Pflaum CD, , Dressendorfer RA. 1996. Immunofunctional assay of human growth hormone (hGH) in serum: a possible consensus for quantitative hGH measurement. J Clin Endocrinol Metab, 81:2613\u20132620.","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/256495a0"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyp394"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-2680"},{"key":"e_1_3_3_50_2","first-page":"121","volume-title":"Werner and Ingbar's The Thyroid","author":"Chopra IJ","year":"2000","unstructured":"Chopra IJ, , Sabatino L. 2000. Nature and sources of circulating thyroid hormones. In: Braverman LE, , Utinger RD (eds) Werner and Ingbar's The Thyroid. Lippincott Williams & Wilkins, Philadelphia, PA, pp 121\u2013135."},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-57-1-66"},{"key":"e_1_3_3_52_2","volume-title":"Program of the 79th Annual Meeting of the American Thyroid Association","author":"Geraci T","year":"2008","unstructured":"Geraci T, , Fjeld C, , Colasurdo V, , Samuels M, , Schuff K, , Scanlan T. 2008. 3-Iodothyronamine (T1AM) levels in human serum and tissue. Program of the 79th Annual Meeting of the American Thyroid Association, Chicago, IL."},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-2680"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-010-3705-9"}],"container-title":["Thyroid\u00ae"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/thy.2013.0688","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/thy.2013.0688","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/thy.2013.0688","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T05:57:03Z","timestamp":1777701423000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/thy.2013.0688"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9]]},"references-count":53,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2014,9]]}},"alternative-id":["10.1089\/thy.2013.0688"],"URL":"https:\/\/doi.org\/10.1089\/thy.2013.0688","relation":{},"ISSN":["1050-7256","1557-9077"],"issn-type":[{"value":"1050-7256","type":"print"},{"value":"1557-9077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9]]}}}