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Thyroid hormone has many effects on the human body. It plays an essential role in growth and development, thermogenesis, oxygen consumption, and the metabolism of carbohydrates, lipids, and proteins. Although thyroid hormone is essential for the normal function of many tissues, thyroid dysfunction is frequently insidious and may be missed.
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The hypothalamic-pituitary-thyroid axis is finely tuned to maintain stable levels of thyroid hormone in the body. Thyrotropin-releasing hormone (TRH) is produced in the hypothalamus and stimulates the production and secretion of thyroid-stimulating hormone (TSH) by the anterior pituitary gland.1 Through binding of the thyroid-stimulating hormone receptor (TSHR), TSH leads to production and release of the thyroid hormones, thyroxine (T4) and triiodothyroxine (T3), as well as thyroid cell growth. Thyroid hormones feedback on the anterior pituitary and hypothalamus, decreasing secretion of TSH and TRH, respectively, allowing for tight regulation of thyroid hormone concentrations. The predominant form of hormone secreted by the thyroid is T4, which then undergoes peripheral conversion to T3 by types I and III deiodinases. T3, the metabolically active hormone, and exerts its effects by binding nuclear receptors and influencing DNA transcription. T4 may also be converted into the inactive reverse T3 (rT3) by deiodinase type III. Increased rT3 is commonly seen in the fetus and in severely ill patients.1
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The majority of thyroid hormone circulates bound to thyroid-binding globulin (TBG) and to a lesser extent, other serum proteins. The remainder circulates unbound (free) and is metabolically active. Estrogen decreases TBG clearance, leading to higher levels of total thyroid hormone. As a result, oral contraceptive pill use or pregnancy will lead to elevated total T4 levels, but the free amount of thyroid hormone remains normal.
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The maturity level of the hypothalamic-pituitary-thyroid axis must be considered to correctly interpret thyroid function tests in newborns and children. At birth, an acute surge in TSH occurs in response to exposure to the cold extrauterine environment, resulting in a rise in T4 and T3 levels. TSH remains elevated for 3 to 5 days after birth while the T4 and T3 levels gradually decline over the first 2 to 4 weeks of life.2 During childhood, there is a progressive decrease in TSH and thyroid hormone levels until approximately age 15 to 16 years, when adult levels are reached (Table 69-1).
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