Thyroid Metabolic Hormones
Endemic Colloid Goiter Caused by Dietary Iodide Deficiency.
"Goiter" means a greatly enlarged thyroid gland. Lack of iodine - No production of thyroxine and triiodothyronine. pituitary secretes excessively large quantities of TSH. TSH then stimulates the thyroid cells to secrete tremendous amounts of thyroglobulin colloid into the follicles, and the gland grows larger and larger. However, because of lack of iodine, thyroxine and triiodothyronine production does not occur in the thyroglobulin molecule and therefore does not cause the normal suppression of TSH production by the anterior pituitary. The follicles become tremendous in size, and the thyroid gland may increase to 10 to 20 times its normal size.
Diseases of the Thyroid
1. Hyperthyroidism (Toxic Goiter, Thyrotoxicosis, Graves' Disease) the thyroid gland is increased to two to three times its normal size hyperplastic glands secrete thyroid hormone at rates 5 to 15 times normal Graves' disease- the most common form of hyperthyroidism, Autoimmune disease- antibodies called thyroid-stimulating immunoglobulins (TSIs) form against the TSH receptor in the thyroid gland. Thyroid Adenoma. adenoma (a tumor) in the thyroid tissue secretes large quantities of thyroid hormone Symptoms of Hyperthyroidism (1) a high state of excitability, (2) intolerance to heat, (3) increased sweating, (4) mild to extreme weight loss (sometimes as much as 100 pounds), (5) varying degrees of diarrhea, (6) muscle weakness, (7) nervousness or other psychic disorders, (8) extreme fatigue but inability to sleep, and (9) tremor of the hands.
Synthesis and Secretion of the Thyroid Metabolic Hormones
93% - thyroxine 7% - triiodothyronine All the thyroxine is eventually converted to triiodothyronine in the tissues, so both are functionally important Triiodothyronine is about four times as potent as thyroxine, but it is present in the blood in much smaller quantities and persists for a much shorter time compared with thyroxine.
Iodine Is Required for Formation of Thyroxine
About 50 milligrams of ingested iodine in the form of iodides or about 1 mg/week. To prevent iodine deficiency, common table salt is iodized with about 1 part sodium iodide to every 100,000 parts sodium chloride.
Most of the Thyroxine Secreted by the Thyroid Is Converted to Triiodothyronine
Before acting on the genes to increase genetic transcription, one iodide is removed from almost all the thyroxine, thus forming triiodothyronine. Intracellular thyroid hormone receptors have a high affinity for triiodothyronine. Consequently, more than 90 percent of the thyroid hormone molecules that bind with the receptors is triiodothyronine.
Effect on Plasma and Liver Fats
Decreased Body Weight. Increased Blood Flow and Cardiac Output. Increased Heart Rate.
Idiopathic Nontoxic Colloid Goiter.
Enlarged thyroid glands in people who do not have iodine deficiency. These goitrous glands may secrete normal quantities of thyroid hormones, but more frequently, the secretion of hormone is depressed, as in endemic colloid goiter. The exact cause of the enlarged thyroid gland in patients with idiopathic colloid goiter is not known Thyroiditis- causes slight hypothyroidism, -increased TSH secretion and progressive growth of the gland. 1. A deficient iodide-trapping mechanism- iodine is not pumped adequately into the thyroid cells 2. A deficient peroxidase system- iodides are not oxidized to the iodine state 3. Deficient coupling of iodinated tyrosines in the thyroglobulin molecule so that the final thyroid hormones cannot be formed
Physiological Characteristics of Hypothyroidism.
Fatigue and extreme somnolence, with persons sleeping up to 12 to 14 hours a day Extreme muscular sluggishness, a slowed heart rate, decreased cardiac output, decreased blood volume Sometimes increased body weight, Mental sluggishness, Development of an edematous appearance throughout the body called myxedema.
Iodide Pump—The Sodium-Iodide Symporter (Iodide Trapping)
First stage- formation of thyroid hormones- transport of iodides from the blood into the thyroid glandular cells and follicles. The basal membrane of the thyroid cell has the specific ability to pump the iodide actively to the interior of the cell. This pumping is achieved by the action of a sodium-iodide symporter This process of concentrating the iodide in the cell is called iodide trapping Rate of iodide trapping by the thyroid is influenced by- TSH
Hypothyroidism
Hashimoto's disease- autoimmunity against the thyroid gland In this case the autoimmunity destroys the gland rather than stimulates it. Autoimmune "thyroiditis," - thyroid inflammation. Thyroiditis causes progressive deterioration and finally fibrosis of the gland other type of hypothyroidism- thyroid goiter (enlarged thyroid glands)
Thyroid Hormones Increase Cellular Metabolic Activity
Increase the metabolic activities of almost all the tissues of the body. The basal metabolic rate (BMR) can increase- 60 to 100% above normal when large quantities of the hormones are secreted. The rate of utilization of foods for energy is greatly accelerated. Although the rate of protein synthesis is increased, at the same time the rate of protein catabolism is also increased. The growth rate of young people is greatly accelerated. The mental processes are excited, and the activities of most of the other endocrine glands are increased.
Effect on Plasma and Liver Fats
Increased thyroid hormone decreases the concentrations of cholesterol, phospholipids, and triglycerides in the plasma, even though it increases the free fatty acids. Conversely, decreased thyroid secretion greatly increases the plasma concentrations of cholesterol, phospholipids, and triglycerides and almost always causes excessive deposition of fat in the liver as well. The large increase in circulating plasma cholesterol in prolonged hypothyroidism is often associated with severe atherosclerosis
Feedback Effect of Thyroid Hormone to Decrease Anterior Pituitary Secretion of TSH
Increased thyroid hormone in the body fluids decreases secretion of TSH by the anterior pituitary. When the rate of thyroid hormone secretion rises to about 1.75 times normal, the rate of TSH secretion falls essentially to zero. Almost all this feedback depressant effect occurs even when the anterior pituitary has been separated from the hypothalamus. Increased thyroid hormone inhibits anterior pituitary secretion of TSH mainly by a direct effect on the anterior pituitary gland itself. Maintain an almost constant concentration of free thyroid hormones in the circulating body fluids.
Fate of Ingested Iodides.
Iodides ingested orally are absorbed from the gastrointestinal tract into the blood in about the same manner as chlorides.
The thyroid gland
Located- below the larynx on each side of and anterior to the trachea One of the largest of the endocrine glands- 15 to 20 grams in adults. Secretes two major hormones; thyroxine (T4) and triiodothyronine (T3) Increase the metabolic rate of the body Secretion is controlled by thyroid-stimulating hormone (TSH) secreted by the anterior pituitary gland.
Exophthalmos.
Most people with hyperthyroidism exhibit some degree of protrusion of the eyeballs This condition is called exophthalmos. Much more often, the eyes are damaged because the eyelids do not close completely when the person blinks or is asleep. As a result, the epithelial surfaces of the eyes become dry and irritated and often infected, resulting in ulceration of the cornea. The cause of the protruding eyes is edematous swelling of the retro-orbital tissues and degenerative changes in the extraocular muscles.
Myxedema.
Myxedema - almost total lack of thyroid hormone function. bagginess under the eyes and swelling of the face.
Regulation of Thyroid Hormone Secretion
TSH (thyrotropin) - increases secretion of thyroxine and triiodothyronine by the thyroid gland. Increased proteolysis of the thyroglobulin- releasing the thyroid hormones into the circulating blood Increased activity of the iodide pump, which increases the rate of "iodide trapping" in the glandular cells Increased iodination of tyrosine to form the thyroid hormones Increased size and increased secretory activity of the thyroid cells
Antithyroid Substances Suppress Thyroid Secretion
Thiocyanate Ions- Decrease Iodide Trapping. Propylthiouracil (methimazole and carbimazole)- Decreases Thyroid Hormone Formation
Physiological Functions of the Thyroid Hormones
Thyroid Hormones Increase Transcription of Large Numbers of Genes. The general effect of thyroid hormone is to activate nuclear transcription of large numbers of genes Therefore, in virtually all cells of the body, great numbers of protein enzymes, structural proteins, transport proteins, and other substances are synthesized. The net result is a generalized increase in functional activity throughout the body.
Other functions
Thyroid Hormones Increase the Number and Activity of Mitochondria. Increase Active Transport of Ions through Cell Membranes. In children with hypothyroidism, the rate of growth is greatly retarded. Promote growth and development of the brain during fetal life and for the first few years of postnatal life. If the fetus does not secrete sufficient quantities of thyroid hormone, growth and maturation of the brain both before birth and afterward are greatly retarded and the brain remains smaller than normal.
Physiological Anatomy of the Thyroid Gland
Thyroid gland is composed of large numbers of closed follicles (100 to 300 micrometers in diameter) That are filled with a secretory substance called colloid and lined with cuboidal epithelial cells that secrete into the interior of the follicles. Major constituent of colloid is the large glycoprotein thyroglobulin, which contains the thyroid hormones. The thyroid gland also contains C cells that secrete calcitonin that contributes to regulation of plasma calcium ion concentration
