{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:37:12Z","timestamp":1783489032403,"version":"3.55.0"},"reference-count":32,"publisher":"The Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T00:00:00Z","timestamp":1607040000000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","award":["WI219179"],"award-info":[{"award-number":["WI219179"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Early treatment of primary congenital hypothyroidism (CH) prevents irreversible brain damage. Contrary to primary CH, outcome studies on central CH are scarce. Most patients with central CH have multiple pituitary hormone deficiencies (MPHD); these patients are also at risk for neonatal hypoglycemia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To assess cognitive and motor outcome in patients with early-treated central CH detected by the Dutch neonatal screening.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this cross-sectional study, primary outcome full-scale intelligence quotient (FSIQ) was measured in patients with MPHD and patients with isolated central CH born between January 1, 1995, and January 1, 2015, with siblings as controls. Secondary outcomes were intelligence test subscales and motor function. Linear mixed models were used to compare both patient groups and siblings, followed by post hoc tests in case of significant differences.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Eighty-seven patients (52 MPHD; 35 isolated central CH) and 52 siblings were included. Estimated marginal means for FSIQ were 90.7 (95% CI 86.4-95.0) in patients with MPHD and 98.2 (95% CI 93.0-103.5) in patients with isolated central CH. While patients with MPHD scored lower FSIQs than siblings (mean difference \u20137.9 points, 95% CI \u201313.4 to \u20132.5; P\u2005=\u2005.002), patients with isolated central CH did not. Processing speed was lower in both patient groups than in siblings (mean differences \u201310.5 and \u201310.3 points). Motor difficulties occurred significantly more often in patients (33%) versus siblings (5%; P\u2005=\u2005.004).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>In early-treated central CH, FSIQ is comparable with siblings in patients with isolated central CH, while patients with MPHD have a significantly lower FSIQ. This may be explained by disease-specific consequences of MPHD, such as neonatal hypoglycemia and more severe hypothyroidism.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa901","type":"journal-article","created":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T01:37:04Z","timestamp":1607045824000},"page":"e1231-e1239","source":"Crossref","is-referenced-by-count":18,"title":["Cognitive and Motor Outcome in Patients with Early-Detected Central Congenital Hypothyroidism Compared with Siblings"],"prefix":"10.1210","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3787-0811","authenticated-orcid":false,"given":"Jolanda C","family":"Naafs","sequence":"first","affiliation":[{"name":"Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, department of Pediatric Endocrinology, Amsterdam, The Netherlands"},{"name":"Amsterdam UMC, University of Amsterdam, department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology & Metabolism, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Pieter","family":"Marchal","sequence":"additional","affiliation":[{"name":"Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, Pediatric Psychosocial Department, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8048-9050","authenticated-orcid":false,"given":"Eric","family":"Fliers","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, University of Amsterdam, department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology & Metabolism, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul H","family":"Verkerk","sequence":"additional","affiliation":[{"name":"TNO, Department of Child Health, CE Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8016-2859","authenticated-orcid":false,"given":"Michiel A J","family":"Luijten","sequence":"additional","affiliation":[{"name":"Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, Pediatric Psychosocial Department, Amsterdam, The Netherlands"},{"name":"Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Epidemiology and Biostatistics, Amsterdam Public Health research institute, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4994-2918","authenticated-orcid":false,"given":"Anita","family":"Boelen","sequence":"additional","affiliation":[{"name":"Endocrine Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9677-7441","authenticated-orcid":false,"given":"A S Paul","family":"van Trotsenburg","sequence":"additional","affiliation":[{"name":"Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, department of Pediatric Endocrinology, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0318-5541","authenticated-orcid":false,"given":"Nitash","family":"Zwaveling-Soonawala","sequence":"additional","affiliation":[{"name":"Emma Children\u2019s Hospital, Amsterdam UMC, University of Amsterdam, department of Pediatric Endocrinology, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,12,3]]},"reference":[{"issue":"5","key":"2021122117345016100_CIT0001","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/S0022-3476(72)80542-0","article-title":"Improved prognosis in congenital hypothyroidism treated before age three months","volume":"81","author":"Klein","year":"1972","journal-title":"J Pediatr."},{"issue":"4","key":"2021122117345016100_CIT0002","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1210\/jc.2017-01937","article-title":"Mean high-dose l-thyroxine treatment is efficient and safe to achieve a normal IQ in young adult patients with congenital hypothyroidism","volume":"103","author":"Aleksander","year":"2018","journal-title":"J Clin Endocrinol Metab."},{"issue":"9","key":"2021122117345016100_CIT0003","doi-asserted-by":"crossref","first-page":"3663","DOI":"10.1210\/jc.2013-1903","article-title":"Neurodevelopmental and body composition outcomes in children with congenital hypothyroidism treated with high-dose initial replacement and close monitoring","volume":"98","author":"Albert","year":"2013","journal-title":"J Clin Endocrinol Metab."},{"issue":"2","key":"2021122117345016100_CIT0004","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.beem.2013.05.008","article-title":"Screening for congenital hypothyroidism: a worldwide view of strategies","volume":"28","author":"Ford","year":"2014","journal-title":"Best Pract Res Clin Endocrinol Metab."},{"issue":"1","key":"2021122117345016100_CIT0005","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1542\/peds.2004-2162","article-title":"Clinical effectiveness and cost-effectiveness of the use of the thyroxine\/thyroxine-binding globulin ratio to detect congenital hypothyroidism of thyroidal and central origin in a neonatal screening program","volume":"116","author":"Lanting","year":"2005","journal-title":"Pediatrics."},{"issue":"2","key":"2021122117345016100_CIT0006","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1159\/000358198","article-title":"European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism","volume":"81","author":"L\u00e9ger","year":"2014","journal-title":"Horm Res Paediatr."},{"issue":"6","key":"2021122117345016100_CIT0007","doi-asserted-by":"crossref","first-page":"3350","DOI":"10.1210\/jc.2004-2444","article-title":"Neonatal detection of congenital hypothyroidism of central origin","volume":"90","author":"van Tijn","year":"2005","journal-title":"J Clin Endocrinol Metab."},{"issue":"2","key":"2021122117345016100_CIT0008","doi-asserted-by":"crossref","first-page":"E297","DOI":"10.1210\/jc.2014-2871","article-title":"The severity of congenital hypothyroidism of central origin should not be underestimated","volume":"100","author":"Zwaveling-Soonawala","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2021122117345016100_CIT0009","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/j.jpeds.2009.12.011","article-title":"Newborn screening results in children with central hypothyroidism","volume":"156","author":"Nebesio","year":"2010","journal-title":"J Pediatr."},{"issue":"12","key":"2021122117345016100_CIT0010","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1007\/s40618-014-0139-9","article-title":"Diagnostic pitfalls in the assessment of congenital hypopituitarism","volume":"37","author":"Cavarzere","year":"2014","journal-title":"J Endocrinol Invest."},{"issue":"6","key":"2021122117345016100_CIT0011","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1530\/EJE-20-0833","article-title":"Clinical and genetic characteristics of Dutch children with central congenital hypothyroidism, early detected by neonatal screening","volume":"183","author":"Naafs","year":"2020","journal-title":"Eur J Endocrinol."},{"key":"2021122117345016100_CIT0012","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.earlhumdev.2016.12.009","article-title":"An emerging evidence base for the management of neonatal hypoglycaemia","volume":"104","author":"Harding","year":"2017","journal-title":"Early Hum Dev."},{"issue":"10","key":"2021122117345016100_CIT0013","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1001\/jamapediatrics.2017.1579","article-title":"Association of neonatal glycemia with neurodevelopmental outcomes at 4.5 years","volume":"171","author":"McKinlay","year":"2017","journal-title":"JAMA Pediatr."},{"issue":"3","key":"2021122117345016100_CIT0014","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1530\/EJE-19-0874","article-title":"Cognitive outcome in congenital central hypothyroidism: a systematic review with meta-analysis of individual patient data","volume":"182","author":"Naafs","year":"2020","journal-title":"Eur J Endocrinol."},{"issue":"4","key":"2021122117345016100_CIT0015","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1007\/s11065-012-9215-0","article-title":"Assessment of intelligence in the preschool period","volume":"22","author":"Baron","year":"2012","journal-title":"Neuropsychol Rev"},{"issue":"12","key":"2021122117345016100_CIT0016","doi-asserted-by":"crossref","first-page":"4564","DOI":"10.1210\/jc.2016-2531","article-title":"Mutations in TBL1X are associated with central hypothyroidism","volume":"101","author":"Heinen","year":"2016","journal-title":"J Clin Endocrinol Metab."},{"issue":"7","key":"2021122117345016100_CIT0017","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.paed.2015.03.007","article-title":"Understanding hypopituitarism","volume":"25","author":"Webb","year":"2015","journal-title":"Paediatr Child Health."},{"issue":"2","key":"2021122117345016100_CIT0018","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1093\/jpepsy\/27.2.121","article-title":"Quantifying practice effects in longitudinal research with the WISC-R and WAIS-R: a study of children and adolescents with hemophilia and male siblings without hemophilia","volume":"27","author":"Sirois","year":"2002","journal-title":"J Pediatr Psychol."},{"issue":"Pt 3","key":"2021122117345016100_CIT0019","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1348\/000709903322275911","article-title":"Psychometric properties of the movement assessment battery for children-checklist as a screening instrument for children with a developmental co-ordination disorder","volume":"73","author":"Schoemaker","year":"2003","journal-title":"Br J Educ Psychol."},{"issue":"3","key":"2021122117345016100_CIT0020","article-title":"Test statistics for comparing two proportions with partially overlapping samples","volume":"10","author":"Derrick","year":"2015","journal-title":"J Appl Quant Methods"},{"issue":"1","key":"2021122117345016100_CIT0021","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting linear mixed-effects models using lme4","volume":"67","author":"Bates","year":"2015","journal-title":"J Stat Software"},{"issue":"10","key":"2021122117345016100_CIT0022","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1136\/jmedgenet-2017-105113","article-title":"Mutations in IRS4 are associated with central hypothyroidism","volume":"55","author":"Heinen","year":"2018","journal-title":"J Med Genet."},{"issue":"6","key":"2021122117345016100_CIT0023","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/S0022-3476(05)83178-6","article-title":"Motor and cognitive development in children with congenital hypothyroidism: a long-term evaluation of the effects of neonatal treatment","volume":"124","author":"Kooistra","year":"1994","journal-title":"J Pediatr."},{"issue":"2","key":"2021122117345016100_CIT0024","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1210\/jc.2005-1209","article-title":"Intellectual and motor development of young adults with congenital hypothyroidism diagnosed by neonatal screening","volume":"91","author":"Kempers","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"2021122117345016100_CIT0025","doi-asserted-by":"crossref","first-page":"102","DOI":"10.6065\/apem.2017.22.2.102","article-title":"Intellectual development in preschool children with early treated congenital hypothyroidism","volume":"22","author":"Seo","year":"2017","journal-title":"Ann Pediatr Endocrinol Metab."},{"issue":"5","key":"2021122117345016100_CIT0026","doi-asserted-by":"crossref","first-page":"R199","DOI":"10.1530\/EJE-19-0168","article-title":"Diagnosis of endocrine disease: pituitary stalk interruption syndrome: etiology and clinical manifestations","volume":"181","author":"Vergier","year":"2019","journal-title":"Eur J Endocrinol."},{"issue":"2","key":"2021122117345016100_CIT0027","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1210\/jc.2012-2731","article-title":"All-cause and disease-specific mortality and morbidity in patients with congenital hypothyroidism treated since the neonatal period: a national population-based study","volume":"98","author":"Azar-Kolakez","year":"2013","journal-title":"J Clin Endocrinol Metab."},{"issue":"3","key":"2021122117345016100_CIT0028","first-page":"149","article-title":"Compound heterozygous and homozygous mutations of the TSHbeta gene as a cause of congenital central hypothyroidism in Europe","volume":"62","author":"Karges","year":"2004","journal-title":"Horm Res."},{"issue":"6","key":"2021122117345016100_CIT0029","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1111\/cen.12947","article-title":"Mild deficits in attentional control in patients with the IGSF1 deficiency syndrome","volume":"84","author":"Joustra","year":"2016","journal-title":"Clin Endocrinol (Oxf)."},{"key":"2021122117345016100_CIT0030","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/B978-0-12-404697-9.00012-1","article-title":"Chapter 12\u2014WISC-V and the personalized assessment approach","volume-title":"WISC-V Assessment and Interpretation.","author":"Holdnack","year":"2016"},{"issue":"1","key":"2021122117345016100_CIT0031","first-page":"12","article-title":"Cognitive profiles of patients with early detected and treated congenital hypothyroidism","volume":"115","author":"Pardo Campos","year":"2017","journal-title":"Arch Argent Pediatr."},{"issue":"10","key":"2021122117345016100_CIT0032","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1111\/j.1365-2826.2004.01243.x","article-title":"Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings","volume":"16","author":"Zoeller","year":"2004","journal-title":"J Neuroendocrinol."}],"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\/dgaa901\/35436011\/dgaa901.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/106\/3\/e1231\/41832416\/dgaa901.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/106\/3\/e1231\/41832416\/dgaa901.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T18:02:42Z","timestamp":1640109762000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/106\/3\/e1231\/6019991"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,3]]},"references-count":32,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,12,3]]},"published-print":{"date-parts":[[2021,3,8]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgaa901","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,3,1]]},"published":{"date-parts":[[2020,12,3]]}}}