The thyroid gland is supplied with a rich blood flow and is drained by three sets of veins on each side: the superior, middle, and inferior thyroid veins. It receives sympathetic innervation that affects blood vessels but not secretion.
The thyroid follicle is the functional unit of the gland, surrounded by a single layer of thyroid epithelial cells. It is approximately 200 to 300 µm in diameter and sits on a basal lamina. The follicle contains colloid, which is filled with thyroglobulin, a large protein secreted by the epithelial cells. Thyroid hormones are produced on this scaffold. The size of the epithelial cells and the amount of colloid vary with gland activity. Within the gland, there are also parafollicular cells, or C cells, which produce the hormone calcitonin.
The thyroid gland secretes iodothyronines, a class of hormones formed by the coupling of two iodinated tyrosine molecules. The primary product is thyroxine (T4), which is a prohormone. The active form of thyroid hormone is triiodothyronine (T3), which accounts for about 10% of the thyroid output. Less than 1% of the thyroid output is reverse T3 (rT3), which is inactive. T4, T3, and rT3 are normally secreted in the same proportions they are stored in the gland.
Since T4 is the primary product but T3 is the active form of thyroid hormone, peripheral conversion is crucial. Thyronine-specific deiodinases play a key role in this conversion. The type 1 deiodinase (D1) converts T4 to T3 in tissues with high blood flow, such as the liver and kidneys. This provides basal circulating T3 for uptake by other tissues. D1 is also expressed in the thyroid and has relatively low affinity for T4. Interestingly, D1 levels are increased in hyperthyroidism, contributing to elevated circulating T3 levels.
Fig. 42.1). Typically the two lobes are connected by a midventral isthmus. The thyroid gland receives a rich blood supply. It is drained by three sets of veins on each side: the superior, middle, and inferior thyroid veins. The thyroid gland receives sympathetic innervation that is vasomotor but not secretomotor.
The functional unit of the thyroid gland is the thyroid follicle, a spherical structure about 200 to 300 µm in diameter that is surrounded by a single layer of thyroid epithelial cells (
Fig. 42.2 ). The epithelium sits on a basal lamina, the outermost structure of the follicle, and is surrounded by a rich capillary supply. The apical side of the follicular epithelium faces the lumen of the follicle. The follicular lumen itself is filled with colloid, which is composed of thyroglobulin. This large (660 kDa) protein is secreted into the lumen and iodinated by the thyroid epithelial cells, serving as a scaffold for production of thyroid hormones. The size of the epithelial cells and the amount of colloid are dynamic features that change with activity of the gland. The thyroid gland contains another type of cell in addition to follicular cells. Scattered within the gland are parafollicular cells, or C cells, which are the source of the polypeptide hormone calcitonin (see
Production of Thyroid Hormones
The secretory products of the thyroid gland are iodothyronines (
Fig. 42.3 ), a class of hormones formed by the coupling of two iodinated tyrosine molecules. Approximately 90% of the thyroid output is 3,5,3′,5′-tetraiodothyronine (thyroxine, or T4). T4 is primarily a prohormone. About 10% is 3,5,3′-triiodothyronine (T3), which is the active form of thyroid hormone. Less than 1% of thyroid output is 3,3′,5′-triiodothyronine (reverse T3, or rT3), which is inactive. Normally these three products are secreted in the same proportions at which they are stored in the gland.
Because the primary product of the thyroid gland is T4, yet the active form of thyroid hormone is T3, the thyroid axis relies heavily on peripheral conversion through the action of thyronine-specific deiodinases (see
Fig. 42.3 ). Most • Fig. 42.1 A and B, Anatomy of the thyroid gland. C, Image of pertechnetate uptake by a normal thyroid gland. (Modified from Drake RL et al. Gray’s Anatomy for Students. Philadelphia: Churchill Livingstone; 2005.) conversion of T4 to T3 by type 1 deiodinase (D1) occurs in tissues with high blood flow and rapid exchange with plasma, such as the liver and kidneys. This process supplies basal circulating T3 for uptake by other tissues in which local T3 generation is low or absent. D1 is also expressed in the thyroid (again, where T4 is abundant) and has relatively low affinity (i.e., a Km of 1 µM) for T4. Levels of D1 are paradoxically increased in hyperthyroidism and contribute to the elevated circulating T3 levels in this disease.