The normal thyroid gland secretes sufficient amounts of the thyroid hormones—triiodothyronine (T3) and tetraiodothyronine (T4, thyroxine)—to normalize growth and development, body temperature, and energy levels. These hormones contain 59% and 65% (respectively) of iodine as an essential part of the molecule. Calcitonin, the second type of thyroid hormone, is important in the regulation of calcium metabolism and is discussed in Chapter 42.
The recommended daily adult iodide (I−)† intake is 150 mcg (200 mcg during pregnancy and lactation and up to 250 mcg for children).
* This chapter is dedicated to Dr. Francis S. Greenspan, co-author, mentor, colleague, and friend who will be sorely missed by his many colleagues and by his patients for his kindness, generosity, and expert care as chief of the Thyroid Clinic at UCSF.
†In this chapter, the term “iodine” denotes all forms of the element; the term “iodide” denotes only the ionic form, I−
Iodide, ingested from food, water, or medication, is rapidly absorbed and enters an extracellular fluid pool. The thyroid gland removes about 75 mcg a day from this pool for hormone synthesis, and the balance is excreted in the urine. If iodide intake is increased, the fractional iodine uptake by the thyroid is diminished.
Biosynthesis of Thyroid Hormones
Once taken up by the thyroid gland, iodide undergoes a series of enzymatic reactions that incorporate it into active thyroid hormone (Figure 38–1). The first step is the transport of iodide into the thyroid gland by an intrinsic follicle cell basement membrane protein called the sodium/iodide symporter (NIS). This can be inhibited by large doses of iodides as well as anions (eg, thiocyanate (SCN−), pertechnetate (TcO4−), and perchlorate (CIO4−). At the apical cell membrane a second I− transport enzyme called pendrin controls the flow of iodide across the membrane. Pendrin is also found in the cochlea of the inner ear. If pendrin is deficient or absent (SLC26A4 mutation), a hereditary syndrome of goiter and deafness, called Pendred syndrome (PDS), ensues. At the apical – – – −I−ProteolysisI°MIT-DIT-T3-T4 Transport PeroxidaseOrganification Thyroid gland Thyroglobulin Peripheral tissues T4, T3 Blood Iodides –Iodides, thioamides
SCN–, ClO4
T4, T3 – Radiocontrast media, °-blockers, corticosteroids, amiodarone
FIGURE 38–1 Biosynthesis of thyroid hormones. The sites of action of various drugs that interfere with thyroid hormone biosynthesis are shown.
cell membrane, iodide is oxidized by thyroidal peroxidase (TPO) to iodine, in which form it rapidly iodinates tyrosine residues within the thyroglobulin molecule to form monoiodotyrosine (MIT) and diiodotyrosine (DIT). This process is called iodide organification. Thyroidal peroxidase is transiently blocked by high levels of intrathyroidal iodide and blocked more persistently by thioamide drugs. Gene expression of TPO is stimulated by thyroid-stimulating hormone (TSH).