{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T23:31:01Z","timestamp":1776468661996,"version":"3.51.2"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T00:00:00Z","timestamp":1634601600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007786","name":"National Center for Child Health and Development","doi-asserted-by":"publisher","award":["2019\u20102021"],"award-info":[{"award-number":["2019\u20102021"]}],"id":[{"id":"10.13039\/100007786","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Thyroid dysfunction is common in patients with Down syndrome (DS), the most common chromosomal disorder. Thyroid hormones (THs) are important for normal growth, neurodevelopment, and metabolism, highlighting the importance of quantifying the levels in patients with DS. However, current methods possess cross\u2010reactivity that results in inaccuracies in quantification. We aimed at developing a new analytical method for quantifying the total 3,3\u2032,5\u2010triiodo\u2010<jats:sc>l<\/jats:sc>\u2010thyronine (TT3), total 3,3\u2032,5,5\u2032\u2010tetraiodo\u2010<jats:sc>l<\/jats:sc>\u2010thyronine (TT4), 3,3\u2032,5\u2032\u2010triiodo\u2010<jats:sc>l<\/jats:sc>\u2010thyronine, and reverse T3 (rT3) levels using LC\u2013MS\/MS. Repeatability and reproducibility with coefficient of variation values of 2\u20139 and 3\u201313%, respectively, were acceptable, suggesting that the assay was suitable for measuring serum THs. We measured the serum TH levels of patients with DS but without thyroid dysfunction (age, 3\u201320\u2009years) and compared the levels to those of controls (patients with idiopathic short stature; age, 3\u201317\u2009years). When TH levels were summarized by age group, the serum TT4 concentrations were not significantly different between the controls and patients with DS across all age groups. Meanwhile, the serum TT3 concentrations differed according to age. In addition, the serum rT3 concentrations were significantly higher in patients with DS than in controls, except for those in the 12\u201314 age group. We also calculated the T3\/T4 and rT3\/T4 ratios to elucidate the reason for the higher rT3 in patients with DS; however, no useful findings were obtained. Thus, further investigation is needed to clarify our findings.<\/jats:p>","DOI":"10.1002\/bmc.5249","type":"journal-article","created":{"date-parts":[[2021,9,26]],"date-time":"2021-09-26T22:01:58Z","timestamp":1632693718000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Quantification of serum thyroid hormones using tandem mass spectrometry in patients with Down syndrome"],"prefix":"10.1002","volume":"36","author":[{"given":"Reiko","family":"Iwano","sequence":"first","affiliation":[{"name":"Clinical Research Institute Kanagawa Children\u2019s Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Machiko","family":"Toki","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Kanagawa Children's Medical Center  Yokohama Japan"},{"name":"Department of Pediatrics Keio University School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko","family":"Hanakawa","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumi","family":"Asakura","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masanori","family":"Adachi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukichi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Clinical Research Institute Kanagawa Children\u2019s Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1810-9894","authenticated-orcid":false,"given":"Koji","family":"Muroya","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,10,19]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"36","article-title":"Prevalence of thyroid dysfunctions in infants and children with down syndrome (DS) and the effect of thyroxine treatment on linear growth and weight gain in treated subjects versus DS subjects with normal thyroid function: A controlled study","volume":"90","author":"AlAaraj N.","year":"2019","journal-title":"Acta BioMedica"},{"key":"e_1_2_9_3_1","first-page":"132","article-title":"Thyroid disorders in subjects with down syndrome: An update","volume":"89","author":"Amr N. H.","year":"2018","journal-title":"Acta BioMedica"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7902-8_8"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.23.1.0455"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2011-0007"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-11-0002"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/44.3.440"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000381543"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.5603\/EP.a2018.0087"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpem-2018-0537"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2016.02.039"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(84)80544-2"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2004.049536"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2012.08.008"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000362450"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/hvaa022"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2014.06.007"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.79.3.242"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2014.04.032"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11845-013-0994-y"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38219"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-019-0218-2"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac020361s"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12374"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1515\/JPEM.2008.21.2.155"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3164\/jcbn.17-55"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-0535"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1159\/000457952"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-019-01941-9"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2018.06.052"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0138864"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/1824-7288-38-44"},{"key":"e_1_2_9_34_1","first-page":"172","article-title":"Age\u2010related patterns of thyroid\u2010stimulating hormone response to thyrotropin\u2010releasing hormone stimulation in down syndrome","volume":"145","author":"Sharav T.","year":"1991","journal-title":"American Journal of Diseases of Children"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2010.07.020"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cccn.2004.01.007"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1177\/2042018820922688"},{"issue":"2","key":"e_1_2_9_38_1","first-page":"96","article-title":"Assessing thyroid functions in children with down's syndrome","volume":"6","author":"Tayrab E.","year":"2017","journal-title":"International Journal of Advances in Pharmacy, Biology and Chemistry"},{"key":"e_1_2_9_39_1","volume-title":"Bioanalytical method validation: Guidance for industry","author":"U.S. Department of Health and Human Services. Food and Drug Administration","year":"2018"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2010.154088"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021303"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-010-3705-9"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-16-0193"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2016.11.022"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.34172\/aim.2020.31"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-16-0858"}],"container-title":["Biomedical Chromatography"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bmc.5249","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bmc.5249","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bmc.5249","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T20:14:26Z","timestamp":1760040866000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bmc.5249"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,19]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1002\/bmc.5249"],"URL":"https:\/\/doi.org\/10.1002\/bmc.5249","archive":["Portico"],"relation":{},"ISSN":["0269-3879","1099-0801"],"issn-type":[{"value":"0269-3879","type":"print"},{"value":"1099-0801","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,19]]},"assertion":[{"value":"2021-04-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e5249"}}