ESPE Abstracts

Background: Congenital primary hypothyreoidism occurs in about 1 of 3 600 life births and is usually detected with newborn screening. Early levothyroxine treatment is the prerequisite for normal psychomotor development of affected children. However, patients suffering from congenital central hypothyroidism are missed by the screening procedure, which may lead to delayed diagnosis and therapy. In very rare cases central hypothyroidism is caused by isolated TSH deficiency due to mutations in the TSHB gene.

Case presentation: A 1.5 year old boy of non-consanguineous parents presented at the age of 5 months because of feeding problems and weight loss. On admission he was in poor condition and suffered from a severe RSV infection requiring artificial ventilation. He had pale skin, umbilical hernia, short stature and marked developmental delay. The boy had already been hospitalized twice because of icterus prolongatus, meteorism and feeding problems, unfortunately without recognition of the severe hypothyroidism. A very low TSH (0.17 mU/l) in combination with unmeasurable fT₄ and T₃ led to the suspicion of isolated TSH deficiency. Sequencing revealed a homozygous mutation c.373delT; p.Cys125Valfs*10 in the TSHB gene. Interestingly, this particular mutation (formerly named C105V or 313ΔT) has already been described as a homozygous mutation in a couple of German families without obvious consanguinity, indicating a founder mutation. Levothyroxine treatment was immediately started. At age 14 months Bayley scales of infant development revealed a developmental age of 9–10 months, absent speech but fortunately no hearing deficit.

Conclusion: Central hypothyroidism is still a clinical challenge, as it is not detected in newborn screening. Paediatric endocrinologists should therefore advice their paediatric colleagues about this syndrome and its clinical picture. TSHB gene mutations should be considered in cases with very low TSH with preservation of other pituitary axes and normal pituitary MRI.