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Thyroid gland Thyroid glands are located in the neck, in close approximation to the first part of the trachea. In humans, the thyroid gland has a "butterfly"

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Presentation on theme: "Thyroid gland Thyroid glands are located in the neck, in close approximation to the first part of the trachea. In humans, the thyroid gland has a "butterfly""— Presentation transcript:

1 Thyroid gland Thyroid glands are located in the neck, in close approximation to the first part of the trachea. In humans, the thyroid gland has a "butterfly" shape, with two lateral lobes that are connected by a narrow section called the isthmus.

2 Thyroid & parathyroid glands Most animals, however, have two separate glands on either side of the trachea. Thyroid glands are brownish-red in color. Close examination of a thyroid gland will reveal one or more small, light- colored nodules on or protruding from its surface - these are parathyroid glands

3 Histologic appearance of thyroid gland The microscopic structure of the thyroid is quite distinctive. Thyroid epithelial cells - the cells responsible for synthesis of thyroid hormones - are arranged in spheres called thyroid follicles. Follicles are filled with colloid, a proteinaceous depot of thyroid hormone precursor. In the low (left) and high-magnification (right) images of a cat thyroid below, follicles are cut in cross section at different levels, appearing as roughly circular forms of varying size. In standard histologic preparations such as these, colloid stains pink.

4 Synthesis and Secretion of Thyroid Hormones The entire synthetic process occurs in three major steps: –Production and accumulation of the raw materials –Synthesis of the hormones on a backbone or scaffold of precursor –Release of the free hormones from the scaffold and secretion into blood

5 Two principle raw materials needed Tyrosines are provided from a large glycoprotein scaffold called thyroglobulin, which is synthesized by thyroid epithelial cells and secreted into the lumen of the follicle - colloid is essentially a pool of thyroglobulin. A molecule of thyroglobulin contains 134 tyrosines, although only a handful of these are actually used to synthesize T4 and T3. Iodine, or more accurately iodide (is taken up from blood by thyroid epithelial cells, which have on their outer plasma membrane a sodium-iodide symporter or "iodine trap". Once inside the cell, iodide is transported into the lumen of the follicle along with thyroglobulin.

6 Synthesis, continued Synthesis of thyroid hormones is conducted by the enzyme thyroid peroxidase, an integral membrane protein present in the apical (colloid- facing) plasma membrane of thyroid epithelial cells. Thyroid peroxidase catalyzes two sequential reactions: –Iodination of tyrosines on thyroglobulin (also known as "organification of iodide”.( –Synthesis of thyroxine or triiodothyronine from two iodotyrosines.

7 Synthesis, continued Through the action of thyroid peroxidase, thyroid hormones accumulate in colloid, on the surface of thyroid epithelial cells. Remember that hormone is still tied up in molecules of thyroglobulin - the task remaining is to liberate it from the scaffold and secrete free hormone into blood.

8 Release of thyroid hormones Thyroid hormones are excised from their thyroglobulin scaffold by digestion in lysosomes of thyroid epithelial cells. This final act in thyroid hormone synthesis proceeds in the following steps: Thyroid epithelial cells ingest colloid by endocytosis from their apical borders - that colloid contains thyroglobulin decorated with thyroid hormone. Colloid-laden endosomes fuse with lysosomes, which contain hydrolytic enzymes that digest thyroglobluin, thereby liberating free thyroid hormones. Finally, free thyroid hormones apparently diffuse out of lysosomes, through the basal plasma membrane of the cell, and into blood where they quickly bind to carrier proteins for transport to target cells.

9 Control of Thyroid Hormone Synthesis and Secretion Thyroid-stimulating hormone, also known as thyrotropin, is secreted from cells in the anterior pituitary called thyrotrophs, finds its receptors on epithelial cells in the thyroid gland, and stimulates that gland to synthesize and release thyroid hormones. TSH is a glycoprotein hormone composed of two subunits which are non-covalently bound to one another. The most important controller of TSH secretion is thyroid-releasing hormone. Thyroid-releasing hormone is secreted by hypothalamic neurons into hypothalamic-hypophyseal portal blood, finds its receptors on thyrotrophs in the anterior pituitary and stimulates secretion of TSH.

10 Control of Thyroid Hormone Synthesis and Secretion Feedback mechanism Neurons in the hypothalamus secrete thyroid releasing hormone (TRH), which stimulates cells in the anterior pituitary to secrete thyroid-stimulating hormone (TSH) TSH binds to receptors on epithelial cells in the thyroid gland, stimulating synthesis and secretion of thyroid hormones, which affect probably all cells in the body. When blood concentrations of thyroid hormones increase above a certain threshold, TRH-secreting neurons in the hypothalamus are inhibited and stop secreting TRH. This is an example of "negative feedback".

11 Control of Thyroid Hormone Synthesis and Secretion, continued Each of the processes described above appears to be stimulated by thyroid-stimulating hormone from the anterior pituitary gland. Binding of TSH to its receptors on thyroid epithelial cells stimulates synthesis of the iodine transporter, thyroid peroxidase and thyroglobulin. The magnitude of the TSH signal also sets the rate of endocytosis of colloid - high concentrations of TSH lead to faster rates of endocytosis, and hence, thyroid hormone release into the circulation. Conversely, when TSH levels are low, rates of thyroid hormone synthesis and release diminish.

12 Thyroid Hormone Receptors and Mechanism of Action Receptors for thyroid hormones are intracellular DNA-binding proteins that function as Thyroid hormones enter cells through membrane transporter proteins. A number of plasma membrane transporters have been identified, some of which require ATP hydrolysis; the relative importance of different carrier systems is not yet clear and may differ among tissues. Once inside the nucleus, the hormone binds its receptor, and the hormone-receptor complex interacts with specific sequences of DNA in the promoters of responsive genes. The effect of the hormone- receptor complex binding to DNA is to modulate gene expression, either by stimulating or inhibiting transcription of specific genes. hormone-responsive transcription factors.

13 Physiologic Effects of Thyroid Hormones It is likely that all cells in the body are targets for thyroid hormones. Thyroid hormones have profound effects on many physiologic processes, such as development, growth and metabolism. Many of the effects of thyroid hormone have been delineated by study of deficiency and excess states.

14 Metabolism Thyroid hormones stimulate diverse metabolic activities in most tissues, leading: –increase in basal metabolic rate. body heat production, which seems to result, at least in part, from increased oxygen consumption and rates of ATP hydrolysis. Examples of specific metabolic effects of thyroid hormones include: –Lipid metabolism: Increased thyroid hormone levels stimulate: fat mobilization, leading to increased concentrations of fatty acids in plasma. enhance oxidation of fatty acids in many tissues. plasma concentrations of cholesterol and triglycerides are inversely correlated with thyroid hormone levels - one diagnostic indication of hypothyroidism is increased blood cholesterol concentration. –Carbohydrate metabolism: Thyroid hormones stimulate almost all aspects of carbohydrate metabolism, including enhancement of : insulin-dependent entry of glucose into cells increased gluconeogenesis and glycogenolysis to generate free glucose.

15 Growth & Development Growth: Thyroid hormones are clearly necessary for normal growth in children and young animals, as evidenced by the growth- retardation observed in thyroid deficiency. Development: A classical experiment in endocrinology was the demonstration that tadpoles deprived of thyroid hormone failed to undergo metamorphosis into frogs. Of critical importance in mammals is the fact that normal levels of thyroid hormone are essential to the development of the fetal and neonatal brain.

16 Growth & Development, continued Thyroid Hormones and Fetal Brain Development In 1888 the Clinical Society of London issued a report underlining the importance of normal thyroid function on development of the brain. Since that time, numerous studies with rats, sheep and humans have reinforced this concept, usually by study of the effects of fetal and/or maternal thyroid deficiency. Thyroid hormones appear to have their most profound effects on the terminal stages of brain differentiation, including synaptogenesis, growth of dendrites and axons, myelination and neuronal migration.

17 Other Effects Cardiovascular system: Thyroid hormones increases heart rate, cardiac contractility and cardiac output. They also promote vasodilatation, which leads to enhanced blood flow to many organs. Central nervous system: Both decreased and increased concentrations of thyroid hormones lead to alterations in mental state. Too little thyroid hormone, and the individual tends to feel mentally sluggish, while too much induces anxiety and nervousness.. Essential for development of synapses and myelination of nerves. Reproductive system: Normal reproductive behavior and physiology is dependent on having essentially normal levels of thyroid hormone. Hypothyroidism in particular is commonly associated with infertility.

18 Disorders of Thyroid Hypothyroidism Hypothyroidism is the result from any condition that results in thyroid hormone deficiency. Two well-known examples include: Iodine deficiency: Iodide is absolutely necessary for production of thyroid hormones; without adequate iodine intake, thyroid hormones cannot be synthesized. Historically, this problem was seen particularly in areas with iodine-deficient soils, and frank iodine deficiency has been virtually eliminated by iodine supplementation of salt. Primary thyroid disease: Inflammatory diseases of the thyroid that destroy parts of the gland are clearly an important cause of hypothyroidism.

19 Symptoms Critinism: –Mental retardation –In- proportionate musclo-skeletal growth, e.g. protruded tongue, short limbs compared to the trunk, dry skin, –Constipation. –Husky voice –Intolerance to cold. –Reproductive failure Adult: –lethargy, fatigue, cold-intolerance, weakness, hair loss, infertility. Weight gain, sleepy, If these signs are severe, the clinical condition is called myxedema

20 Hyperthyroidism Causes: results from secretion of thyroid hormones due to: –In humans the most common form of hyperthyroidism is Graves disease, an immune disease in which autoantibodies bind to and activate the thyroid-stimulating hormone receptor, leading to continual stimulation of thyroid hormone synthesis. Another interesting, but rare cause of hyperthyroidism is so-called hamburger thyrotoxicosis –Secretory tumor of thyroid or pituitary gland. Manifestations: –Common signs include nervousness, insomnia, high heart rate, eye disease and anxiety. Graves disease is commonly treated with anti-thyroid drugs (e.g. propylthiourea, methimazole), which suppress synthesis of thyroid hormones primarily by interfering with iodination of thyroglobulin by thyroid peroxidase.thyroid peroxidase

21 Goiter Definition: –Enlargement of thyroid gland Causes: –Iodine deficiency: Epidemics :as in oasis Repeated pregnancy.

22 Hyperthyroidism Symptoms of hyperthyroidism (overactive thyroid) include: fatigue or tiredness weight loss hair loss bulging eyes soft nails nervousness and irritability rapid or irregular heartbeat (i.e., arrhythmia) increased perspiration feeling hot when others are not, or trouble withstanding the heat irregular or scant menstrual periods trouble getting pregnant or infertility more frequent bowel movements or diarrhea troubled or disturbed sleep weakness in muscles (e.g., can't easily walk up stairs or lift heavy objects) tremors or trembling hands eye irritation or problems seeing an enlarged thyroid (i.e., goiter), which may appear as a swelling at the base of the neck (American College of Obstetricians and Gynecologists, 1999; American Foundation of Thyroid Patients, 1994; Mayo Clinic, 2002b; National Women's Health Information Center, 2002; The Hormone Foundation, 2002a).

23 Screenings, Tests, and Exams To diagnose a thyroid disorder, your doctor will first ask for your medical history and perform a physical exam. Your doctor will feel and observe the lower region of your neck for any noticeable enlargement or nodules (lumps). He/she may also ask you to lift your neck and swallow several times while observing and feeling your neck to help detect any type of mass (American Academy of Otolaryngology, 2002). Blood tests, particularly the TSH (thyroid stimulating hormone) test, may be done to detect levels of thyroid hormone in the blood. In fact, all newborn babies are screened for hypothyroidism using a blood test. It is especially important to perform this test and treat a baby with hypothyroidism in the first few weeks of life since hypothyroidism can effect growth and normal development (Nemours Foundation, 2003) -- impacting both physical and mental growth/function. The TSH test has also been proposed as a cost-effective health screening for thyroid disorder among men and women aged 35 and older (American Medical Women's Association, 1999a; American Medical Women's Association, 1999b). The American Thyroid Association recommends that adults older than age 35 be screened for thyroid disease using the TSH test every five years (American Association for Clinical Chemistry, 2001). Screening is of particular importance because thyroid disorders can go on for a long time without producing symptoms, and may increase cholesterol levels (American Medical Women's Association, 1999b). Other blood tests your doctor may perform are antibody tests and calcitonin tests. Your doctor may also want you to have an ultrasound examination of your neck and thyroid. This is a painless test that allows the doctor to see a picture (sonogram) of the thyroid using ultrasonic waves. Typically, in this test, a technician will smear a cool gel onto a round, flat instrument that is then moved lightly across the neck region. A thyroid scan is another test for thyroid disorders. In this test, the patient is asked to drink a small amount of radioactive iodine. A special camera is then used to detect the areas of the thyroid gland that absorbed the radioactive iodine -- these are the problem areas (American College of Obstetricians and Gynecologists, 1999). If a lump (nodule) is diagnosed/detected, your doctor may recommend a fine needle aspiration biopsy. This is a safe and relatively painless procedure where a hypodermic needle is passed into the lump and samples of tissue are taken out. This procedure will provide the doctor more information about the nature of the lump, and especially differentiate between a benign (non-cancerous) and malignant (cancerous) mass (American Academy of Otolaryngology, 2002). Additionally, a chest x-ray, CT (computed tomography) scan or MRI (magnetic resonance imaging) scan, which makes images of tissues and organs, may be performed if more information is needed. Note: Be sure to tell your doctor about any medications you are taking, as they may interfere with thyroid gland function tests (American Association for Clinical Chemistry, 2001).

24 Graves' disease The most common form of hyperthyroidism is a condition known as Grave's disease. Graves' disease is a type of autoimmune disease (see box on autoimmune disease) in which the immune system over stimulates the thyroid gland (National Women's Health Information Center, 2000b).see box on autoimmune disease Person's with Grave's disease may experience: anxiety irritability difficulty sleeping rapid, forceful, or irregular heartbeat fine tremor of the hands or fingers increase in perspiration sensitivity to heat weight loss, despite normal diet enlargement of the thyroid gland (i.e., goiter) light menstrual periods frequent bowel movements.

25 Particularly related to Graves' disease are eye symptoms, known as Graves' opthalmopathy. In Graves' opthalmopathy, the eye protrudes beyond its protective orbit because tissues and muscles behind the eye swell. This condition can result in: drying of the front of the eye excess tearing sensation of sand or grit in the eye(s) reddened or inflamed eyes widening of the space between the eyelids swelling of the lids and tissue around the eyes bulging eyes decreased blinking and excessive staring light sensitivity blurry or double vision limited eye movement.

26 Treatments for Graves' disease include: Medications -- anti-thyroid drugs, which inhibit production or conversion of the active thyroid hormone Radioactive iodine -- iodine damages thyroid cells to shrink the thyroid gland, thus reducing hormone levels Surgery -- a subtotal thyroidectomy, in which a surgeon removes most of the thyroid gland and renders it incapable of overproducing thyroid hormone (National Graves' Disease Foundation, 2000; National Women's Health Information Center, 2000b).

27 What is Goiter? A goiter is an abnormal enlargement of the thyroid gland and can occur for a number of different reasons. The thyroid is a small, butterfly- shaped gland inside the neck, just below your Adam’s apple. The thyroid gland produces hormones which control the body’s metabolism and regulate the rate at which the body carries out its functions. The presence of goiter usually means that the thyroid gland is not functioning normally. It can occur in a gland that is overactive, producing too much hormone (hyperthyroidism), or that is underactive, producing too little hormone (hypothyroidism). Goiter puts pressure on other parts of the neck such as the trachea and esophagus - making it difficult to breathe and swallow. Often, goiters are also removed for cosmetic reasons. They are more common in women and the elderly.

28 What are the Causes of Goiter? There are various different types of goiter, each with their own specific causes. Iodine Deficiency - Iodine found in fish products, drinking water and table salt, is essential for the production of thyroid hormone. If there is a lack of it, an individual will suffer from hypothyroidism. In an effort to produce more thyroid hormone the thyroid gland is over stimulated and enlarges to form an endemic goiter. An iodine deficiency is very common in underdeveloped countries.



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