Congenital hypothyroidism (CH) is the most frequent neonatal endocrine disorder and
the most common preventable cause of development delay and growth failure if diagnosed
and treated early. The thyroid is the first endocrine gland to develop during embryonic
life and to be recognizable in humans. Thyroid development and maturation can be divided
into 2 phases: a first phase of embryogenesis and a second phase of folliculogenesis
and differentiation with thyroid hormone production at the final steps. Regulation
of the thyroid function requires normal development of the hypothalamic-pituitary-thyroid
axis, which occurs during the embryonic and neonatal period. Defects in any of steps
of thyroid development, differentiation, and regulation lead to permanent CH. Newborn
screening programs, established in only one-third of countries worldwide, detect CH
and are cost-effective and highly sensitive and specific. During the last decade,
epidemiology of CH has changed with increased frequency of thyroid in situ in primary
CH. Advances in molecular testing have expanded knowledge and understanding of thyroid
development and function. However, a molecular cause is identified in only 5% of CH
due to thyroid dysgenesis. The purpose of this article is to describe the clinical
approach to the child with CH, focusing on diagnostic work-up and future challenges
on optimizing thyroid replacement therapy and regenerative medicine. The review is
written from the perspective of the case of 2 girls referred for CH after newborn
screening and diagnosed with thyroid ectopy. The genetic work-up revealed novel mutations
in TUBB1 gene, associated with large platelets and abnormal platelet physiology.
