Treatment of congenital thyroid dysfunction: Achievements and challenges

The active thyroid hormone tri-iodothyronine (T3) is essential for a normal development of children. Especially within the first years of life, thyroid hormone is pivotal in enabling maturation of complex brain function and somatic growth. The most compelling example for a life without thyroid hormone are those historical cases of children who came to birth without a thyroid gland – as shown in autopsy-studies- and who suffered from untreated hypothyroidism, at that time initially called “sporadic congenital hypothyroidism” (CH). In the last decades huge achievements resulted in a normal development of these children based on newborn screening programs that enable an early onset of a high dose LT4-treatment. Further progress will be necessary to further tailor an individualized thyroid hormone substitution approach and to identify those more complex patients with congenital hypothyroidism and associated defects, who will not benefit from an even optimized LT4 therapy.Besides the primary production of thyroid hormone a variety of further mechanisms are necessary to mediate the function of T3 on normal development that are located downstream of thyroid hormone production. Abnormalities of these mechanisms include the MCT8-transport defect, deiodinase-insufficiency and thyroid hormone receptor alpha-and beta defects. These thyroid hormone resistant diseases can not be treated with classical LT4 substitution alone. The development of new treatment options for those rare cases of thyroid hormone resistance is one of the most challenging tasks in the field of congenital thyroid diseases today.