Thyroid hormone has a significant role in promoting growth and maturation. During midgestation, a crucial amount of thyroid hormone crosses the placenta and the fetal thyroid axis becomes functional. Proper neurological development and bone formation in the fetus rely heavily on thyroid hormone. Insufficient thyroid hormone during infancy leads to congenital hypothyroidism, characterized by irreversible intellectual disability and short stature.

Thyroid hormone has several effects on bone, hard tissue, and the dermis. It promotes endochondral ossification, linear bone growth, and the maturation of epiphyseal bone centers. The maturation and activity of chondrocytes in the cartilage growth plate are enhanced by T3, partially through increasing the production and action of local growth factors. T3 also supports the actions of growth hormone, insulinlike growth factor (IGF)-I, and other growth factors during linear postnatal growth. Additionally, T3 plays a role in normal adult bone remodeling.

Thyroid hormone influences the progression of tooth development and eruption, as well as the growth and maturation cycle of the epidermis, hair follicles, and nails. Abnormalities in thyroid hormone levels can result in hair loss and abnormal nail formation. Thyroid hormone stimulates the normal degradative processes in these tissues. It also regulates the structure of subcutaneous tissue by inhibiting the synthesis and increasing the degradation of mucopolysaccharides (glycosaminoglycans) and fibronectin in the extracellular connective tissue.

The nervous system is regulated by thyroid hormone in terms of timing and pace of development. Inadequate thyroid hormone levels during fetal and early infancy stages hinder the growth of the cerebral and cerebellar cortex, axon proliferation, dendrite branching, synaptogenesis, myelination, and cell migration. If neonatal thyroid hormone deficiency is not promptly recognized and treated, irreversible impairment of the central nervous system (CNS) occurs. These morphological defects are accompanied by biochemical abnormalities such as decreased cell size, RNA and protein content, tubulin and microtubule-associated protein, myelin protein and lipid content, local production of critical growth factors, and rates of protein synthesis.

Thyroid hormone also impacts various functions of the nervous system including wakefulness, alertness, responsiveness to stimuli, auditory sense, hunger awareness, memory, and learning capacity. Proper availability of thyroid hormone is essential for maintaining normal emotional tone. Furthermore, thyroid hormone increases the speed and amplitude of peripheral nerve reflexes and the motility of the gastrointestinal tract.

In both men and women, thyroid hormone plays a permissive role in the regulation of reproductive function. Deviations in thyroid hormone levels from the normal range disrupt the normal ovarian cycle of follicular development, maturation, and ovulation, as well as the testicular process of spermatogenesis. Additionally, maintaining a healthy pregnant state is dependent on thyroid hormone levels. These detrimental effects may be attributed, in part, to alterations in the metabolism or availability of steroid hormones. For instance, thyroid hormone stimulates hepatic synthesis and release of sex steroid–binding globulin.

Hypothyroidism refers to the insufficient production of thyroid hormones and can occur as primary, secondary, or tertiary endocrine disease. In primary hypothyroidism, T4 and T3 levels are abnormally low and TSH is high. In secondary and tertiary hypothyroidism, both thyroid hormones and TSH are low. The response of TSH levels to synthetic TRH can be utilized to distinguish between pituitary and hypothalamic disease.
A major effect of thyroid hormone is to promote growth and maturation. A small but crucial amount of thyroid hormone crosses the placenta, and the fetal thyroid axis becomes functional at midgestation. Thyroid hormone is extremely important for normal neurological development and proper bone formation in the fetus. In infants, insufficient fetal thyroid hormone causes congenital hypothyroidism, characterized by irreversible intellectual disability and short stature (see In the Clinic box).
Effects on Bone, Hard Tissue, and Dermis
Thyroid hormone promotes endochondral ossification, linear bone growth, and maturation of the epiphyseal bone centers. T3 enhances maturation and activity of chondrocytes in the cartilage growth plate, in part by increasing local growth factor production and action. During linear postnatal growth, T3 supports the actions of growth hormone, insulinlike growth factor (IGF)-I, and other growth factors. T3 also supports normal adult bone remodeling.
The progression of tooth development and eruption depends on thyroid hormone, as does the normal cycle of growth and maturation of the epidermis, its hair follicles, and nails. The normal degradative processes in these structural and integumentary tissues are stimulated by thyroid hormone. Thus either too much or too little thyroid hormone can lead to hair loss and abnormal nail formation. Thyroid hormone regulates the structure of subcutaneous tissue by inhibiting synthesis and increasing degradation of mucopolysaccharides (glycosaminoglycans) and fibronectin in the extracellular connective tissue (see later description of myxedema).
Effects on the Nervous System
Thyroid hormone regulates the timing and pace of development of the CNS. Thyroid hormone deficiency in utero and in early infancy inhibits growth of the cerebral and cerebellar cortex, proliferation of axons and branching of dendrites, synaptogenesis, myelination, and cell migration. Irreversible CNS impairment results when neonatal thyroid hormone deficiency is not recognized and treated promptly. These morphological defects are paralleled by biochemical abnormalities. Decreased thyroid hormone levels reduce cell size, RNA and protein content, tubulinand microtubuleassociated protein, protein and lipid content of myelin, local production of critical growth factors, and rates of protein synthesis.
Thyroid hormone also enhances wakefulness, alertness, responsiveness to various stimuli, auditory sense, awareness of hunger, memory, and learning capacity. In addition, normal emotional tone depends on proper thyroid hormone availability. Furthermore the speed and amplitude of peripheral nerve reflexes are increased by thyroid hormone, as is motility of the gastrointestinal tract.
In both women and men, thyroid hormone plays an important permissive role in regulation of reproductive function. The normal ovarian cycle of follicular development, maturation, and ovulation, the homologous testicular process of spermatogenesis, and maintenance of the healthy pregnant state are all disrupted by significant deviations in thyroid hormone levels from the normal range. In part these deleterious effects may be caused by alterations in the metabolism or availability of steroid hormones. For example, thyroid hormone stimulates hepatic synthesis and release of sex steroid–binding globulin.
Hypothyroidism referstoinsufficientproductionofthyroidhormonesandcanoccurasprimary,secondary,ortertiaryendocrinedisease(see ).Inprimaryhypothyroidism,T4andT3levelsareabnormallylowandTSHishigh.Insecondaryandtertiaryhypothyroidism,boththyroidhormonesandTSHarelow.TheresponseofTSHlevelstosyntheticTRHcanbeusedtodistinguishbetweenpituitaryandhypothalamicdisease.