{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T10:10:06Z","timestamp":1756289406452,"version":"3.44.0"},"reference-count":12,"publisher":"BMJ","issue":"1","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2025,1,13]]},"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>TSHB gene mutation results in isolated central congenital hypothyroidism (iCCH). Often diagnosed late, mild neurocognitive impairment is common despite thyroxine initiation. We discuss a female term neonatal presenting with prolonged unconjugated hyperbilirubinaemia. The diagnosis of hypothyroidism was based on strong clinical suspicion, although her thyroid function tests were not felt to fit with the usual appearance of primary thyroid disease. Levothyroxine was started on day 11 of life. On follow-up, the history of low T4 and undetectable TSH at diagnosis plus subsequent normal anterior pituitary hormones and normal pituitary on MRI raised suspicion of iCCH. Genetic analysis revealed deletion involving coding sequence position c.108\u2013109 in exon 2 of TSHB gene. Despite having severe congenital hypothyroidism, timely initiation of levothyroxine averted neurocognitive sequelae. She is on follow-up for 25 years. Early diagnosis and prompt thyroxine initiation are rewarding regardless of the severity of mutation.<\/jats:p>","DOI":"10.1136\/bcr-2024-263094","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T11:56:11Z","timestamp":1738065371000},"page":"e263094","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Central congenital hypothyroidism due to TSHB gene mutation: 25-year follow-up"],"prefix":"10.1136","volume":"18","author":[{"given":"Adlyne Reena","family":"Asirvatham","sequence":"first","affiliation":[{"name":"Endocrinology, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamilnadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vaishnavi Reddy","family":"Deva Reddy","sequence":"additional","affiliation":[{"name":"Genetics, MediScan Systems, Chennai, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sujatha","family":"Jagadeesh","sequence":"additional","affiliation":[{"name":"Clinical Genetics & Genetic Counseling, MediScan Systems, Chennai, Tamil Nadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shriraam","family":"Mahadevan","sequence":"additional","affiliation":[{"name":"Endocrinology Department, Sri Ramachandra Institute of Higher Education and Research, Chennai, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"2025082702350901000_18.1.e263094.1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-1903"},{"key":"2025082702350901000_18.1.e263094.2","doi-asserted-by":"crossref","first-page":"6229","DOI":"10.1210\/jc.2019-00657","article-title":"Genetics of Congenital Isolated TSH Deficiency: Mutation Screening of the Known Causative Genes and a Literature Review","volume":"104","author":"Sugisawa","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"2025082702350901000_18.1.e263094.3","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-18-0383"},{"key":"2025082702350901000_18.1.e263094.4","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1210\/js.2017-00478","article-title":"From Consternation to Revelation: Discovery of a Role for IGSF1 in Pituitary Control of Thyroid Function","volume":"2","author":"Bernard","year":"2018","journal-title":"J Endocr Soc"},{"key":"2025082702350901000_18.1.e263094.5","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-15-0341"},{"key":"2025082702350901000_18.1.e263094.6","doi-asserted-by":"publisher","DOI":"10.1210\/jc.86.4.1600"},{"key":"2025082702350901000_18.1.e263094.7","article-title":"Novel TSHB variant (c.217A>C) causing severe central hypothyroidism and pituitary hyperplasia","volume":"2022","author":"Kaplan","year":"2022","journal-title":"Endocrinol Diabetes Metab Case Rep"},{"key":"2025082702350901000_18.1.e263094.8","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118540"},{"key":"2025082702350901000_18.1.e263094.9","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1089\/thy.2015.0096","article-title":"A TSH\u03b2 Variant with Impaired Immunoreactivity but Intact Biological Activity and Its Clinical Implications","volume":"25","author":"Pappa","year":"2015","journal-title":"Thyroid"},{"key":"2025082702350901000_18.1.e263094.10","doi-asserted-by":"crossref","first-page":"e1231","DOI":"10.1210\/clinem\/dgaa901","article-title":"Cognitive and Motor Outcome in Patients with Early-Detected Central Congenital Hypothyroidism Compared with Siblings","volume":"106","author":"Naafs","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"2025082702350901000_18.1.e263094.11","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1007\/s12098-009-0248-1","article-title":"Central hypothyroidism","volume":"77","author":"Muthukrishnan","year":"2010","journal-title":"Indian J Pediatr"},{"key":"2025082702350901000_18.1.e263094.12","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(86)80276-1"}],"container-title":["BMJ Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bcr-2024-263094","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T09:35:17Z","timestamp":1756287317000},"score":1,"resource":{"primary":{"URL":"https:\/\/casereports.bmj.com\/lookup\/doi\/10.1136\/bcr-2024-263094"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":12,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1,28]]},"published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1136\/bcr-2024-263094"],"URL":"https:\/\/doi.org\/10.1136\/bcr-2024-263094","relation":{},"ISSN":["1757-790X"],"issn-type":[{"type":"electronic","value":"1757-790X"}],"subject":[],"published":{"date-parts":[[2025,1]]}}}