The thyroid gland is a bilobed organ of the endocrine system located in the front of the neck. It secretes hormones that are involved in human development, growth, and metabolism.
The thyroid gland is a small, butterfly-shaped gland made up of two lobes separated by tissue called the isthmus, which lies across the trachea. The lobes of the thyroid are each approximately 2 inches (5 cm) in length, and the isthmus is approximately 2 inches (5 cm) in width and length and the thyroid gland weighs approximately 1 ounce (28 g). Each lobe of the thyroid gland wraps around and is affixed by fibrous tissue to one side of the trachea. A narrow projection of thyroid tissue, called the pyramidal lobe, is often present and originates at the isthmus and extends up to and lays on the surface of the thyroid cartilage (Adam's apple). The upper projections of the right and left lobes are called the upper poles of the gland while the lower projections of the lobes are called the lower poles. The lobes of the thyroid lie between the larynx and trachea medially and the sternomastoid muscles and carotid sheath laterally. The thyroid gland can be felt through palpitation of the neck, unless the neck is very thick and short or the sternomastoid muscles are very well developed.
A thin capsule of connective tissue surrounds the thyroid and divides it into a cluster of globular sacks called follicles. The gland does not, however, have any true subdivisions, and the follicles are packed together like a bag of berries. The follicles are lined with follicular cells that secrete hormones called thyroxine (T4) and triiodothyronine (T3) and enclose a glutinous material called colloid. Colloid is primarily made of a protein called thyroglobulin that is involved in the formation of T4 and T3. Cells called parafollicluar cells or C-cells, which secrete the hormone calcitonin, are found between the follicles.
T3 and T4 hormones
The primary function of the thyroid gland is to produce and secrete T4 and T3, which are hormones involved in many aspects of growth, development, and metabolism. T4 and T3 are produced from thyroglobulin attached to iodide. Iodine obtained from the diet is absorbed through the small intestine, converted into iodide, and transported through the blood stream to the thyroid. The iodide absorbed by the thyroid attaches to thyroglobulin and forms monoiodotyrosine (MIT) and diiodotyrosine (DIT). T4 is formed when two DITs join together and T3 is formed when one MIT joins to one DIT. At this point the T3/T4 are still attached to the thyroglobulin. The thyroglobulin containing T4 and T3 is then transported to the center of the follicle where it forms colloid. When there are low levels of T4 and T3 in the blood, the follicular cells are stimulated to ingest colloid, and digest the thyroglobulin. This ultimately results in the release of T4 and T3 into the blood stream.
REGULATION OF T3 AND T4 SYNTHESIS AND RELEASE. Thyroid stimulating hormone (TSH), which is also called thyrotropin, is the main regulator of thyroid hormone synthesis and release. TSH is produced by the pituitary gland. Binding of TSH to receptors on the thyroid gland stimulates the synthesis and release of T4 and T3. High concentrations of TSH result in increased thyroid hormone synthesis and release into the blood stream, and low levels of TSH result in decreased synthesis and decreased release into the blood stream. The amount of TSH secreted is controlled by the thyroid-releasing hormone, which is produced by an organ called the hypothalamus. When the amount of thyroid hormones in the blood exceeds a certain level, the hypothalamus stops secreting thyroid-releasing hormone. This stops the secretion of TSH, which stops the secretion of T3 and T4. This is called a negative feedback loop. When the levels of thyroid hormones in the blood stream decrease to below a predetermined level then the negative feedback is stopped and the secretion of thyroid-releasing hormone resumes. This ultimately results in resumed secretion of T4 and T3. The amount of T4 and T3 produced can also be influenced by dietary factors such as the amount of iodine consumed and the total caloric intake and can also be affected by inhibitory drugs such as the thionamides.
The thyroid gland also secretes calcitonin. The thyroid's C-cells are stimulated to secrete calcitonin when there is a high concentration of calcium in the blood stream. The function of calcitonin is to inhibit the amount
of resorption of calcium from the bone and to regulate the amount of calcium in the blood stream.
Role in human health
The hormones T4 and T3 produced by the thyroid gland are involved in growth, development and metabolism, and it is likely that most cells are targets for these hormones. Some researchers feel that T4 is only an inactive prohormone while T3 is the biochemically active form of the thyroid hormone. Some T3 is produced in the thyroid but most of it is produced from the conversion of T4 outside of the liver. Receptors on cells bind some T4 but preferentially bind T3. The thyroid hormones stimulate the metabolic activities of most tissues and cause an increase in basal metabolic rate. Normal levels of T4 and T3 are necessary for normal development of the brain and normal growth in childhood. The thyroid hormones are also involved in regulating heart rate and increasing cardiac contractility and output. These hormones also have effects on the central nervous system, since decreased thyroid hormone levels are associated with decreased ability to concentrate and think, and increased levels are associated with anxiety. The reproductive system also requires normal thyroid hormone levels, and decreased levels of these hormones can result in infertility.
Iodine deficiency or excess
Dietary intake of iodine is necessary for the normal synthesis of T3 and T4. A deficiency or excess consumption of iodine can result in a deficiency in these hormones (hypothyroidism) or an excess of these hormones (hyperthyroidism). Iodine deficiency is less common in developed countries where table salt contains iodine. Disorders which lead to a deficiency of iodide in the thyroid can also cause hypothyroidism.
Hypothyroidism is the most common disease of the thyroid and results in deficient production of T4/T3 by the thyroid, or defects, which result in the inability of the body to respond to T4/T3. The clinical manifestations of hypothyroidism include:
- weight gain
- memory and mental impairment and decreased concentration
- loss of libido
- coarseness or loss of hair
- dry skin and cold intolerance
- irregular or heavy menses
- reflex delay
Hypothyroidism is usually confirmed when serum levels of T4 are decreased and serum levels of TSH are increased. In some cases, patients with hypothyroidism can have normal T4 or TSH levels or even low TSH levels. Hypothyroidism is typically treated by oral administration of a synthetic form of T4 called levothyroxine. Hypothyroidism can be classified into primary hypothyroidism, central hypothyroidism and peripheral hypothyroidism.
PRIMARY HYPOTHYROIDISM. Primary hypothyroidism is the most common form of hypothyroidism. Primary hypothyroidism is caused by factors affecting the thyroid gland itself such as thyroid dysgenesis, environmental damage to the thyroid, inherited metabolic defects and environmental factors such as medications
The most common cause of primary hypothyroidism in adults in developed countries is autoimmune thyroiditis (Hashimoto's thyroiditis). Hashimoto's thyroiditis results when the body forms antibodies against the TSH receptors in the thyroid gland. This results in a decreased stimulation of T4/T3 production by the thyroid gland.
CENTRAL HYPOTHYROIDISM. Central hypothyroidism results from insufficient stimulation of the thyroid gland by the thyroid-stimulating hormone (TSH). Central hypothyroidism can result from abnormalities that interfere with the pituitary release of TSH or factors that affect the regulation of TSH by thyroptin releasing hormone (TRH). Central hypothyroidism generally results in low serum levels of T4 and normal to low serum levels of TSH.
PERIPHERAL HYPOTHYROIDISM. Peripheral hypothyroidism is extremely rare and results when the body is unable to respond to thyroxin. The most common cause is thyroid hormone resistance, a rare, autosomal dominant disorder that results from mutations in the thyroid hormone receptor (Trbeta). Increased secretions of T4 and increased T4 in sera and increased levels of TSH characterize this disorder. Patients with this disorder have a 50% percent chance of passing it on to their offspring. Peripheral hypothyroidism can also be caused by massive infantile hemangiomas that excrete high levels of type 3 deiodinase which inactivates T4.
Infants born with hypothyroidism are said to be affected with congenital hypothyroidism. In addition to the typical manifestations of hypothyroidism, congenital hypothyroidism, if untreated, can cause stunted growth, apathy, distended abdomen, swollen tongue, and mental retardation.
Eighty to 90% of cases of congenital hypothryoidism are caused by thyroid dysgenesis. Ten to 15% are due to inherited inborn errors of thyroid hormonogenesis, which are usually autosomal recessive and have a 25% recurrence risk. Congenital hypothyroidism can sometimes be caused by materal radiation treatment during pregnancy or uncontrolled maternal hypothyroidism or hyperthyroidism during pregnancy.
Hyperthyroidism results from an excess amount of T4 and T3 in the blood stream. The major symptoms of hyperthyroidism include nervousness, tremors, sweating,
heat intolerance, palpitations, weight loss with normal caloric intake, amenorrhea, and muscle weakness. In the presence of clinical symptoms the diagnosis of hyperthyroidism can be confirmed when serum measurements indicate increased T4 and/or decreased TSH levels. Hyperthyroidism can be treated through medications such as thionamides, which inhibit the synthesis of T4 and T3, and beta blockers which block the action of thyroid hormones on peripheral cells. Patients who cannot be treated through medications are treated through radioiodine destruction of the thyroid or surgical removal of the thyroid. Surgical removal of the thyroid and sometimes radioiodine treatment can leave the patient permanently hypothyroid.
GRAVES' DISEASE. Graves' disease, the most common cause of hyperthyroidism, is an autoimmune disease resulting from the formation of antibodies against the TSH receptors in the thyroid gland. The only difference between Hashimoto's thyroiditis and Graves' disease is that Graves disease results when these antibodies stimulate thyroid hormone synthesis rather than inhibiting it. Graves' disease results in increased synthesis of T4 and T3, and can result in exophthalmos, thyroid enlargement and goiter, and vitilago. People with Graves' disease may pass on a genetic predisposition and a slightly increased chance of developing Graves' disease to their offspring.
Adenoma—A benign glandular epithelial tumor.
Autosomal dominant—Mutation of only one gene of a pair is required to cause abnormal functioning.
Autosomal recessive—Mutations in both genes of a pair are required to cause abnormal functioning.
Basal metabolic rate—The number of calories that the body consumes when at rest.
Bradycardia—Slowing of the pulse.
Colloid—The gelatinous material made up primarily of thyroglobulin which is found in the follicles of the thyroid.
Cardiac contractility—The ability of the muscles of the heart to contract in the presence of a stimulus.
Endocrine system—A group of organs that secrete hormones directly into the circulatory system that affect metabolism and other body functions.
Exophthalmos—Protrusion of the eyeball.
Goiter—An enlarged thyroid gland resulting in a swelling on the front of the neck.
Hemangioma—Benign tumor made of newly formed blood vessels.
Hormone—A chemical produced by the body which is involved in regulating specific bodily functions such as growth, development, and reproduction.
Hormonogenesis—The production of hormones.
Lobe—Well defined segment of an organ.
Metabolism—Activity by which cells obtain energy from nutrients or use energy to perform basic body functions.
Thyroglobulin—Protein found in the follicles of the thyroid which is involved in the formation of the T4 and T3 hormones produced by the thyroid.
Vitiligo—A skin disorder characterized by depigmented white patches that can have a hyperpigmented border.
OTHER CAUSES OF HYPERTHYROIDISM. Toxic adenoma of the thyroid results from a thyroid nodule that produces additional T4 and T3. This excess production of thyroid hormones results in increased concentrations of T3 and/or T4 in the blood stream and suppression of TSH. Toxic adenoma can be treated through surgical removal of the thyroid, treatment with radioactive iodine, and injection of ethanol into the nodule.
Hyperthyroidism can also be caused by a toxic multinodular goiter. Toxic multinodular goiter is common in areas of iodine deficiency. The multinodular goiter usually results from a goiter caused by hypothyroidism which eventually develops multiple nodules. These nodules produce excess T4 and T3 hormone independent of the TSH levels. Treatment usually involves radioactive iodine or surgery. Hyperthyroidism can also occasionally be caused from abnormalities such as adenomas of the pituitary gland which result in an increased production of TSH. Infections of the thyroid gland can also result in hyperthyroidism. Uncontrolled maternal hyperthyroidism in pregnancy can cause hyperthyroidism in the fetus. In the past hyperthyroidism was occasionally induced when individuals ingested hamburgers containing ground up bovine thyroid gland.
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Lisa Maria Andres, M.S., CGC