Congenital thyroid stimulating hormone (TSH) deficiency occurs due to hypothalamic or pituitary pathology, with consequent impaired stimulation of the thyroid gland by TSH resulting in central congenital hypothyroidism (CCH). Although assumed to be rare, CCH may be more common than previously appreciated with an incidence of up to 1:21 000 reported in the Netherlands. TSH deficiency is most frequently associated with additional pituitary hormone deficits but may also occur in isolation with an estimated incidence of around 1:65 000, often as a result of defects in genes controlling the TSH biosynthetic pathway. Genetic ascertainment in isolated TSH deficiency has advanced over the last three decades, with causative monogenic mutations reported in five different genes: IGSF1, TRHR, TSHB, TBL1X and IRS4. CCH is characterized biochemically by failure of appropriate TSH elevation despite subnormal circulating thyroid hormone levels. Therefore, the primary, TSH-based congenital hypothyroidism screening programmes which operate in the UK will not detect CCH since TSH is not raised. Severe central hypothyroidism may therefore evade diagnosis until the patient presents with clinical sequelae. Adequate circulating thyroid hormone levels are essential for normal childhood growth and neurodevelopment, therefore delayed diagnosis and treatment of CCH may result in profound neurodevelopmental delay. This presentation will focus on the diagnostic pitfalls of CCH, the genetic causes of isolated TSH deficiency, and their associated clinical, biochemical and molecular features.
27 - 29 Nov 2019
British Society for Paediatric Endocrinology and Diabetes