Pharmacology of parathyroid drugs Flashcards
Briefly describe the synthesis of thyroid hormones and the factors which control it
Iodide trapping: The first step is the uptake of iodide from the bloodstream into the thyroid gland. This process is mediated by the sodium-iodide symporter (NIS) present in the thyroid follicular cells.
Oxidation of iodide: Once inside the follicular cells, iodide is oxidized to iodine by the enzyme thyroid peroxidase (TPO), which is located on the apical membrane of the follicular cells.
Iodination of thyroglobulin: Iodine is then covalently attached to tyrosine residues in the protein thyroglobulin (TG) to form monoiodotyrosine (MIT) and diiodotyrosine (DIT). This reaction also occurs on the apical membrane of the follicular cells and is catalyzed by TPO.
Coupling of MIT and DIT: MIT and DIT can then be coupled together to form triiodothyronine (T3) or DIT can be coupled with another DIT to form thyroxine (T4). These reactions occur within the TG molecule and are also catalyzed by TPO.
Proteolysis and secretion: Once synthesized, T3 and T4 are stored within the TG molecule until the gland is stimulated to secrete them. Proteolysis of TG occurs within the follicular cells, releasing T3 and T4 into the bloodstream.
The synthesis of thyroid hormones is controlled by several factors, including:
Thyroid-stimulating hormone (TSH): TSH is produced by the anterior pituitary gland and stimulates the thyroid gland to produce and secrete thyroid hormones.
Iodine availability: Adequate dietary iodine intake is essential for the synthesis of thyroid hormones. Low iodine intake can result in decreased thyroid hormone production.
Negative feedback: High levels of thyroid hormones in the bloodstream can inhibit the secretion of TSH from the pituitary gland, thereby reducing the production of thyroid hormones by the thyroid gland.
Outline the process involved in the release of thyroid hormones
Hypothalamus releases thyrotropin-releasing hormone (TRH): TRH is a hormone secreted by the hypothalamus in response to low levels of thyroid hormones in the blood or other stimuli such as stress or cold temperature.
Pituitary gland releases thyroid-stimulating hormone (TSH): TRH stimulates the pituitary gland to release TSH into the bloodstream. TSH binds to receptors on the thyroid follicular cells and stimulates the synthesis and release of thyroid hormones.
Thyroid gland releases thyroid hormones: TSH activates the enzymes involved in the synthesis of thyroid hormones within the thyroid follicular cells. The hormones, mainly T4 and T3, are then released into the bloodstream from the thyroid gland.
Feedback inhibition: As the levels of thyroid hormones in the bloodstream increase, they inhibit the release of TRH from the hypothalamus and TSH from the pituitary gland, thereby reducing the production and release of thyroid hormones from the thyroid gland. This feedback inhibition helps to maintain the appropriate levels of thyroid hormones in the bloodstream.
Transport and activation: Once released, the majority of T4 is bound to carrier proteins such as thyroxine-binding globulin (TBG), while T3 is mostly free or bound to other proteins. T4 is converted to T3 in peripheral tissues such as the liver, kidneys, and skeletal muscle by the enzyme 5’-deiodinase, which removes an iodine atom from the outer ring of T4. T3 is the more active form of thyroid hormone and is responsible for most of the biological effects of thyroid hormones in the body.
Target cell response: T3 binds to nuclear receptors in target cells, which regulate the transcription of genes involved in various physiological processes, including metabolism, growth, and development. The effects of thyroid hormones are widespread and affect nearly every tissue in the body.
Outline the physiological actions of the thyroid hormones
Metabolism: Thyroid hormones play a crucial role in regulating metabolism. They increase the basal metabolic rate (BMR), which is the amount of energy the body uses at rest. This leads to an increase in oxygen consumption, heat production, and energy expenditure.
Growth and development: Thyroid hormones are essential for normal growth and development, particularly during fetal development and childhood. They are necessary for the development of the nervous system, bones, and muscles.
Cardiovascular system: Thyroid hormones affect the cardiovascular system by increasing heart rate, cardiac output, and blood flow. They also help to maintain normal blood pressure.
Gastrointestinal system: Thyroid hormones stimulate the secretion of digestive enzymes and increase the motility of the gastrointestinal tract, leading to increased absorption of nutrients.
Reproductive system: Thyroid hormones play a crucial role in the regulation of the menstrual cycle and fertility. They also contribute to the development of the mammary glands during pregnancy and lactation.
Central nervous system: Thyroid hormones affect the central nervous system by regulating mood, cognitive function, and behavior. Hypothyroidism can cause depression, fatigue, and impaired cognitive function, while hyperthyroidism can cause anxiety, irritability, and insomnia.
Define the term goitre and understand the reasons for formation of a goitre
A goiter is a swelling or enlargement of the thyroid gland, which is located in the neck just below the Adam’s apple. The thyroid gland produces hormones that regulate metabolism and other bodily functions. When the gland becomes enlarged, it is called a goiter.
There are several reasons why a goiter may form:
Iodine deficiency: The thyroid gland requires iodine to produce hormones. If the body doesn’t get enough iodine through the diet, the thyroid gland may become enlarged as it tries to compensate.
Hyperthyroidism: Hyperthyroidism is a condition in which the thyroid gland produces too much hormone. This can cause the gland to become enlarged.
Hypothyroidism: Hypothyroidism is a condition in which the thyroid gland doesn’t produce enough hormone. In some cases, the gland may become enlarged as it tries to compensate.
Autoimmune diseases: Some autoimmune diseases, such as Hashimoto’s thyroiditis and Graves’ disease, can cause inflammation of the thyroid gland, leading to enlargement.
Thyroid nodules: Thyroid nodules are lumps that form within the thyroid gland. They are usually benign, but in some cases, they can cause the gland to become enlarged.
Discuss the physiological basis for the symptoms in iodine deficiency, hypothyroidism and Graves disease
Iodine deficiency, hypothyroidism, and Graves disease are all conditions related to thyroid function. The thyroid gland produces hormones that play a critical role in regulating metabolism, growth, and development.
Iodine deficiency can result in an enlarged thyroid gland, a condition known as goiter. This is because the thyroid gland requires iodine to produce thyroid hormones, specifically thyroxine (T4) and triiodothyronine (T3). In iodine-deficient regions, the thyroid gland will try to compensate for the lack of iodine by becoming larger. Symptoms of goiter can include a visibly enlarged thyroid gland, difficulty swallowing or breathing, and a hoarse voice.
Hypothyroidism occurs when the thyroid gland does not produce enough thyroid hormone. Symptoms of hypothyroidism can include fatigue, weight gain, cold intolerance, constipation, dry skin, hair loss, and depression. The physiological basis for these symptoms is that thyroid hormones play a critical role in regulating metabolism. When there is not enough thyroid hormone, the body’s metabolic rate decreases, which can lead to the symptoms listed above.
Graves disease is an autoimmune disorder that results in overproduction of thyroid hormone. Symptoms of Graves disease can include weight loss, rapid heartbeat, anxiety, sweating, tremors, and eye problems such as bulging eyes. The physiological basis for these symptoms is that Graves disease is caused by antibodies that stimulate the thyroid gland to produce excess thyroid hormone. This excess hormone leads to an increase in the body’s metabolic rate, which can result in the symptoms listed above.
In summary, iodine deficiency, hypothyroidism, and Graves disease are all conditions related to thyroid function. Iodine deficiency can result in goiter, while hypothyroidism and Graves disease have opposite effects on thyroid hormone production, leading to opposite symptoms. Hypothyroidism results in a decrease in metabolic rate, while Graves disease results in an increase in metabolic rate.
