{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:51:30Z","timestamp":1791478290217,"version":"4.3.4"},"reference-count":4,"publisher":"Walter de Gruyter GmbH","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,26]]},"abstract":"Abstract<\/jats:title>\n \n Objectives<\/jats:title>\n We present a case of central congenital hypothyroidism that was diagnosed clinically in the second month of life, after a false negative neonatal screening test.<\/jats:p>\n <\/jats:sec>\n \n Case presentation<\/jats:title>\n \n A 44-day-old infant presented to the Emergency Department with cyanosis and hypotonia. Examination revealed macroglossia, perioral cyanosis, jaundice, holosystolic murmur, and umbilical hernia. There was a history of early neonatal hospitalization due to feeding difficulties and hypoglycemia; neonatal endocrine-metabolic screening was negative for all tested diseases, including congenital hypothyroidism (whole blood TSH <6.0\u202fmUI\/L). Due to desaturation and bradycardia, the child was admitted to the Pediatric Intensive Care Unit, requiring intubation, mechanical ventilation and, later, a tracheostomy. Metabolic studies showed no abnormalities. Thyroid function tests revealed undetectable TSH and very low free T3 and free T4 levels. Whole exome sequencing revealed a likely pathogenic variant in homozygosity in the\n TSHB<\/jats:italic>\n gene, associated with central congenital hypothyroidism. Levothyroxine was initiated, with rapid normalization of free T4 levels and marked clinical improvement.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Clinical signs of congenital hypothyroidism are becoming increasingly uncommon, due to early screening, diagnosis and treatment; it is still crucial to recognize them, since central congenital hypothyroidism can be missed during routine neonatal screening. This case underscores the importance of starting hormone replacement therapy as early as possible to reduce systemic and cognitive complications.<\/jats:p>\n <\/jats:sec>","DOI":"10.1515\/jpem-2026-0074","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T09:29:32Z","timestamp":1778750972000},"page":"1066-1069","source":"Crossref","is-referenced-by-count":0,"title":["Central congenital hypothyroidism caused by\n TSHB<\/i>\n gene mutation: a case report"],"prefix":"10.1515","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0546-8115","authenticated-orcid":false,"given":"Mariana","family":"Andrade","sequence":"first","affiliation":[{"name":"Pediatrics Department , Unidade Local de Sa\u00fade [Local Health Unit] S\u00e3o Jo\u00e3o , Porto , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Lemos","sequence":"additional","affiliation":[{"name":"Pediatrics Department , Unidade Local de Sa\u00fade [Local Health Unit] S\u00e3o Jo\u00e3o , Porto , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina","family":"Mendon\u00e7a","sequence":"additional","affiliation":[{"name":"Pediatrics Department , Hospital Caldas da Rainha, Unidade Local de Sa\u00fade [Local Health Unit] Oeste , Caldas da Rainha , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Pissarra","sequence":"additional","affiliation":[{"name":"Pediatrics Department , Unidade Local de Sa\u00fade [Local Health Unit] S\u00e3o Jo\u00e3o , Porto , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Grangeia","sequence":"additional","affiliation":[{"name":"Genetics Department , Unidade Local de Sa\u00fade [Local Health Unit] S\u00e3o Jo\u00e3o , Porto , Portugal"},{"name":"Genetics Department, Faculty of Medicine , University of Porto , Porto , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Mota","sequence":"additional","affiliation":[{"name":"Pediatric Intensive Medicine Department , Unidade Local de Sa\u00fade [Local Health Unit] S\u00e3o Jo\u00e3o , Porto , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta Jo\u00e3o","family":"Silva","sequence":"additional","affiliation":[{"name":"Pediatric Intensive Medicine Department , Unidade Local de Sa\u00fade [Local Health Unit] S\u00e3o Jo\u00e3o , Porto , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Tenente","sequence":"additional","affiliation":[{"name":"Pediatrics Department , Unidade Local de Sa\u00fade [Local Health Unit] S\u00e3o Jo\u00e3o , Porto , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00edntia","family":"Castro-Correia","sequence":"additional","affiliation":[{"name":"Pediatrics Department , Unidade Local de Sa\u00fade [Local Health Unit] S\u00e3o Jo\u00e3o , Porto , Portugal"},{"name":"Pediatric Endocrinology and Diabetology Unit, Pediatrics Department , Unidade Local de Sa\u00fade [Local Health Unit] S\u00e3o Jo\u00e3o , Porto , Portugal"},{"name":"Gynecology-Obstetrics and Pediatrics Department, Faculty of Medicine , University of Porto , Porto , Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"2026100815572195831_j_jpem-2026-0074_ref_001","doi-asserted-by":"crossref","unstructured":"Lauffer, P, Zwaveling-Soonawala, N, Naafs, JC, Boelen, A. van Trotsenburg, ASP. Diagnosis and management of central congenital hypothyroidism. Front Endocrinol (Lausanne) 2021;12:686317. https:\/\/doi.org\/10.3389\/fendo.2021.686317.","DOI":"10.3389\/fendo.2021.686317"},{"key":"2026100815572195831_j_jpem-2026-0074_ref_002","doi-asserted-by":"crossref","unstructured":"Instituto Nacional de Sa\u00fade Doutor Ricardo Jorge. Programa Nacional de Rastreio Neonatal\u00a0\u2013\u00a0Relat\u00f3rio 2023. 2023.","DOI":"10.33610\/398039yicvpg"},{"key":"2026100815572195831_j_jpem-2026-0074_ref_003","doi-asserted-by":"crossref","unstructured":"Rose, SR, Wassner, AJ, Wintergerst, KA, Yayah-Jones, NH, Hopkin, RJ, Chuang, J, et al.. Congenital hypothyroidism: screening and management. Pediatrics 2023;151. https:\/\/doi.org\/10.1542\/peds.2022-060420.","DOI":"10.1542\/peds.2022-060419"},{"key":"2026100815572195831_j_jpem-2026-0074_ref_004","doi-asserted-by":"crossref","unstructured":"Schoenmakers, N, Alatzoglou, KS, Chatterjee, VK, Dattani, MT. Recent advances in central congenital hypothyroidism. J\u00a0Endocrinol 2015;227:R51\u201371. https:\/\/doi.org\/10.1530\/joe-15-0341.","DOI":"10.1530\/JOE-15-0341"}],"container-title":["Journal of Pediatric Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jpem-2026-0074\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jpem-2026-0074\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:58:11Z","timestamp":1791475091000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jpem-2026-0074\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,15]]},"references-count":4,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,7,27]]},"published-print":{"date-parts":[[2026,10,26]]}},"alternative-id":["10.1515\/jpem-2026-0074"],"URL":"https:\/\/doi.org\/10.1515\/jpem-2026-0074","relation":{},"ISSN":["0334-018X","2191-0251"],"issn-type":[{"value":"0334-018X","type":"print"},{"value":"2191-0251","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,15]]}}}