Central congenital hypothyroidism due to TSHB gene mutation: 25-year follow-up.

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.108-109 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.