Thyroid Hormone

Thyroid Gland, Role, Regulation,Treatment

1. THYROID HoRMONES Submitted by- Anurag Chourasia M.pharma

2. Contents Thyroid Gland Thyroid Hormones Biosynthesis of Thyroid Hormones Regulation of Thyroid Hormones level Role of Thyroid Hormones Thyroid Diseases Anti Thyroid Drugs Mechanism of action Treatment :Thyroid Surgery References

3. Thyroid Gland - The thyroid gland is the largest, butterfly-shaped endocrine glands & is located at the base of the neck immediately below the Larynx, on each side of & anterior to the trachea. The thyroid gland consists of 2 types of cells: Follicular cells : These are more abundant, and the major secretory cells. They secrete Thyroid hormone. Parafollicular cells or C-cells : These are fewer in number & interspersed. They secrete Calcitonin

4. Thyroid Hormones The Thyroid gland secretes 3 major hormones: Thyroxine or T 4 : having 4 atoms of Iodine. (secreted in largest amount) Triiodothyronine or T 3 : having 3 atoms of Iodine (secreted in lesser amount) Calcitonin: which is an important hormone of calcium metabolism

5. Difference between t4 & t3 The thyroid secretes about 80 micrograms of T4 , but only 5 micrograms of T3 per day. However, T3 has a much greater biological activity (about 10X) than T4. An additional 25 micrograms/day of T3 is produced by peripheral monodeiodination of T4. T4 thyroid I - T3

6. Biosynthesis of Thyroid Hormones Ingestion of iodide Activation of iodide (peroxidase) & iodation of tyrosine Coupling (peroxidase) Release (proteolytic enzyme) Iodide is actively transported to thyroid gland . Iodide is oxidized to iodine by thyroid peroxidase, which in turn iodinates tyrosine residues of the thyroglobulin (TG) to form monoiodotyrosine (MIT) and diiodotyrosine (DIT) , The coupling of two DIT forms T4 and the coupling of one MIT and DIT forms T3. The process of coupling is also catalysed by thyroid peroxidase , T4 and T3 are released by Proteolysis.

7. Biosynthesis of Thyroid Hormones

8. iodine metabolism Dietary iodine is absorbed in the GI tract, then taken up by the thyroid gland (or removed from the body by the kidneys). The transport of iodide into follicular cells is dependent upon a sodium/iodine cotransport system. Iodide taken up by the thyroid gland is oxidized by peroxide in the lumen of the follicle: Oxidized iodine can then be used in production of thyroid hormones. peroxidase I - I +

9. The Next Step: Production of T3 or T4

10. The first Step: Production of thyroglobulin The follicle cells of the thyroid produce thyroglobulin . Thyroglobulin is a very large glycoprotein. Thyroglobulin is released into the colloid space, where it’s tyrosine residues are iodinated by I + . This results in monoiodotyrosine (MIT) or diiodotyrosine (DIT).

11. Initial Steps in Thyroid Hormone Synthesis . follicle cell extracellular space colloid space I - I - thyroglobulin with monoiodotyrosines and diiodotyrosines iodination thyroglobulin thyroglobulin gene I + oxidation I - Na+ Na+ K+

12. Second step: Production of Thyroid Hormones from Iodinated Thyroglobulin The iodinated tyrosine residues on thyroglobulin are modified and joined to form T3 and T4 , still attached to the thyroglobulin molecule.

13. Utilization of Thyroglobulin to Secrete Thyroid Hormones In order to secrete T3/T4, the thyroglobulin in the colloid space is internalized by endocytosis back into the follicle cell. This internalized vesicle joins with a lysosome , whose enzymes cause cleavage of T3 and T4 from thyroglobulin. Some T4 is converted to T3 at this point. T3 and T4 are then released into the extracellular space by diffusion . Only minute amounts of thyroglobulin are released into the circulation.

14. Conversion of T4 to T3 T3 has much greater biological activity than T4. A large amount of T4 (25%) is converted to T3 in peripheral tissues . This conversion takes place mainly in the liver and kidneys . The T3 formed is then released to the blood stream. In addition to T3, an equal amount of “reverse T3” may also be formed. This has no biological activity.

15. Regulation of Thyroid Hormone Levels Thyroid hormone synthesis and secretion is regulated by two main mechanisms: - an “autoregulation” mechanism, which reflects the available levels of iodine - regulation by the hypothalamus and anterior pituitary

16. Autoregulation of Thyroid Hormone Production The rate of iodine uptake and incorporation into thyroglobulin is influenced by the amount of iodide available: - low iodide levels increase iodine transport into follicular cells - high iodide levels decrease iodine transport into follicular cells Thus, there is negative feedback regulation of iodide transport by iodide .

17. Feedback regulation the hypothalamic-pituitary-thyroid axis Hormones derived from the pituitary that regulate the synthesis and/or secretion of other hormones are known as trophic hormones. Key players for the thyroid include: TRH - T hyrotropin R eleasing H ormone TSH - T hyroid S timulating H ormone T 4 /T 3 - Thyroid hormones

18. Role of Thyroid Hormone

19. Thyroid Diseases If your thyroid is too active, it makes more thyroid hormones than your body needs. That condition is hyperthyroidism. Too much thyroid hormone can make you lose weight, speed up your heart rate and make you very sensitive to heat. A thyroid gland that is not active enough, called hypothyroidism, is far more common. It can make you gain weight, feel fatigued and have difficulty dealing with cold temperatures

20. Hyperthyroidism & Hypothyroidism Hyper-secretion or hypo-secretion will induce diseases: Too much secretion hyperthyroidism Too little secretion hypothyroidism

21. Hypothyroidism Hypothyroidism is a condition in which the thyroid gland fails to produce enough thyroid hormone. Complications Untreated hypothyroidism can lead to a number of health problems: Complications- Heart problems. Mental health issues. Myxedema. Birth defects.

22. Hyperthyroidism Hyperthyroidism is a condition caused by an overactive thyroid gland. The gland makes too much T4 and T3 hormones. Complications- > Hyperthyroidism can lead to a number of complications: >Heart problems. >Brittle bones. >Eye problems. People with Graves' ophthalmopathy develop eye problems, including bulging, sensitivity to light, and blurring or double vision. > Thyrotoxic crisis —a sudden intensification of the symptoms, leading to a fever, a rapid pulse and even delirium. If this occurs, seek immediate medical care.

23. Anti Thyroid Drugs

24. Mechanism of Action

25. Adverse effects Typical side effects include Headache, Nausea, Vomiting, Itchy Skin, and Rash, and Muscle Ache and Pain. Serious Lever damage, decreased red and white blood cell synthesis, as well as decrease platelet production have been reported in few cases. The drug’ interaction with other enzymes responsible for clotting factor synthesis accounts for some of these serious side effects. Administering too high a dosage of antithyroid drugs can cause Hypothyroidism.

26. Treatment: thyroid surgery Surgery (thyroidectomy) If you can't tolerate anti-thyroid drugs and don't want to have radioactive iodine therapy, you may be a candidate for thyroid surgery, although this is an option in only a few cases. In a thyroidectomy, your doctor removes most of your thyroid gland. Risks of this surgery include damage to your vocal cords and parathyroid glands — four tiny glands located on the back of your thyroid gland that help control the level of calcium in your blood. In addition, you'll need lifelong treatment with levo -thyroxine to supply your body with normal amounts of thyroid hormone. If your parathyroid glands also are removed, you'll need medication to keep your blood-calcium levels normal.

27. References https://www.google.co.in/imgres?imgurl=https%3A%2F%2Fwebeye.ophth.uiowa.edu%2Feyeforum%2Ftutorials%2Fthyroid-eye-disease%2Flarge%2F24- https://www.slideshare.net/mprasadnaidu/thyroid-hormones-32910296 Shargel Leon , Comprehensive Pharmacy Review, Eighth Edition