ESPE Abstracts

Central congenital hypothyroidism (central CH) refers to an inborn deficient thyroid hormone production due to insufficient pituitary TSH stimulation of an otherwise normal thyroid gland. Central CH may be part of combined pituitary hormone deficiencies (CPHD) (60%) or may occur in isolation. The most common cause of CPHD consists of a characteristic pituitary malformation referred to as pituitary stalk interruption syndrome. Up until 2012 most cases of isolated central CH remained unexplained and only TSHB and TRHR gene variants were described in very rare cases. In the last decade, the use of next generation DNA sequencing techniques, has led to the identification of three new genetic causes of central CH: IGSF1 (2012), TBL1X (2016) and IRS4 (2018). Diagnosing central CH is often challenging since TSH concentrations are normal and diagnosis is based solely on a free T4 concentration below age-specific reference intervals. The lack of neonatal free T4 reference intervals makes diagnosing central CH at the newborn age especially difficult. The Netherlands has a longstanding history of neonatal screening for central CH which enables early detection and treatment. In a recent study on cognitive outcome of early treated Dutch central CH patients, full-scale IQ scores of isolated central CH patients were similar to that of healthy siblings while patients with CPHD had significantly lower full-scale IQ scores (mean of -7.9 points). Unfortunately comparison with late detected patients isn’t possible since systematically collected data on developmental outcomes in these patients is lacking. This leaves the question whether early detection and treatment of central CH improves prognosis unanswered. In this symposium the Dutch experience of screening for central CH will be presented. Challenges in coming to a diagnosis will be highlighted and a practical approach to diagnosis and management of this intriguing condition will be provided.