Congenital Hypothyroidism

Excerpt

Congenital hypothyroidism (CH) is defined as thyroid hormone deficiency present at birth. CH must be diagnosed promptly because delay in treatment can lead to irreversible neurological deficits. Before the newborn screening program, CH was one of the most common preventable causes of intellectual disability. Newborn screening (NBS) programs have led to earlier diagnosis and treatment of CH, resulting in improved neurodevelopmental outcomes.

The thyroid hormone plays an essential role in energy metabolism, growth, and neurodevelopment. Specifically, the thyroid hormone acts on neuronal differentiation, synapsis development, and myelination in the prenatal and newborn periods, regulating central nervous system development. The thyroid hormones are derived from the amino acid tyrosine and produced by the thyroid gland in response to stimulation by the thyroid-stimulating hormone (TSH) produced by the anterior pituitary. TSH is regulated by the thyrotropin-releasing hormone (TRH), which is released from the hypothalamus. This regulation pathway is called the hypothalamic-pituitary-thyroid (HPT) axis. There are two active thyroid hormones, thyroxine (T4) and triiodothyronine (T3).

Both T3 and T4 are secreted by the thyroid gland, though the majority of circulating T3 is derived from peripheral tissue deiodination of T4. Deiodination of T4 to T3 is catalyzed by a group of enzymes known as iodothyronine deiodinases. T4 and T3 inhibit the secretion of TSH, both directly and indirectly, by inhibiting the secretion of TRH. Additional factors that inhibit TSH release are glucocorticoids, somatostatin, and dopamine. Both circulating T4 and T3 are bound tightly to serum proteins, including T4-binding globulin (TBG), and only the tiny fraction of T4 (0.02%) and T3 (0.3%) are unbound, so-called free T4 and free T3, which are biologically active.