1. THYROID GLAND Dr. Hany Ahmed Assistant Professor of Physiology (MD, PhD). Al Maarefa Colleges (KSA) & Zagazig University (ARE) Specialist of Diabetes, Metabolism and Obesity Zagazig Obesity Management & Research Unit Dr. Hany Ahmed Assistant Professor of Physiology (MD, PhD). Al Maarefa Colleges (KSA) & Zagazig University (ARE) Specialist of Diabetes, Metabolism and Obesity Zagazig Obesity Management & Research Unit

2. Objectives The student should be able to: Describe thyroid uptake of iodine. Know basic steps involved in biosynthesis of T3 & T4. Identify the bound forms of T3 and T4 in circulation. Know the biological effects of T3 and T4. Describe the regulation of thyroid hormones secretion. Know thyroid function tests. Identify thyroid hormone receptors. Describe thyroid hormone resistance. Thyrocalcitonin.

3. Physiologic Anatomy of Thyroid Gland Located: immediately below the larynx on each side and anterior to the trachea. Secretes: 1)Thyroxine (T 4 ) 2)Triiodothyronine (T 3 ) 3)Calcitonin.

4. THYROID GLAND  Cells of Thyroid gland: 1- Follicular A Cells secrete Thyroxine (T 4 ) & Tri iodothyronine (T 3 ). 2- Parafollicular C Cells secrete ThyroCalcitonin.  Functions of Thyroid gland: Required for 1- Normal metabolism. 2- Growth & maturation. 3- Ca +2 regulation.

5. Formation & Secretion of thyroid hormones 1) Iodide Trap (iodide pump): It is an active transport mechanism in basal membrane. Intra-cellular thyroid iodide /plasma iodide ratio = 50 : 1 Stimulated by TSH & Inhibited by Thiocyanate & Perchlorate ions. 2) Oxidation of Iodide to Iodine: Oxidation by peroxidase enzyme in apical membrane. Inhibited by Thiouracil & Carbimazol (by Competitive inhibition). 3) Iodination of Tyrosine: Organification of iodine to form Monoiodotyrosine (MIT) & Diiodotyrosine (DIT). Stimulated by TSH & Inhibited by Anti-thyroid drugs.

6. 4- Coupling Reaction: 2 molecules of DIT  Thyroxine (T 4 ) + Alanine. DIT + MIT  Tri iodothyronine (T 3 ) Stimulated by TSH & Inhibited by Antithyroid drugs. 5- Storage: MIT, DIT, T 3 & T 4 are stored in colloid bound to thyroglobulin. 6- Release: Thyroglobulin colloid is taken into the cells by endocytosis then by protease enzyme  release of T 4, T 3, MIT & DIT. Stimulated by TSH && Inhibited by Anti-thyroid drugs. Formation & Secretion of thyroid hormones

7. 7- Deiodination: Lysis of released MIT & DIT by deiodinase enzyme. So, iodine & tyrosine used for new hormonal synthesis (intra thyroidal iodine cycle). 8- Transport of T 3 and T 4 : Bound to plasma proteins and ˂ 1% free. Thyroxine - binding globulin (TBG)  binds T 3 and T 4 Albumin  binds T 3 and T 4. Thyroxine- binding prealbumin (=transthyretin)  binds only T 4 Formation & Secretion of thyroid hormones Thyroxine Binding Globulin (TBG) In circulation, > 99 % of T 3 & T 4 are bound to TBG. In hepatic failure, TBG level decreases →  total thyroid hormones level. In pregnancy, TBG level increases →  total thyroid hormones level.

8. 9- Peripheral Conversions: Peripheral conversions of T 4 to either T 3 (active) or rT3 (inactive). N.B. T 3 is 4 to 5 times more active than T 4

9. Biosynthesis & secretion of thyroid hormones

10. ACTIONS OF THYROID HORMONES

11. 1- Metabolic Actions of thyroid hormones 1)General metabolism (Calorigenesis):  O 2 consumption, heat production,  Na + - K + ATPase activity &  BMR. 2)↑ Blood Glucose: by  glucose GIT absorption. They increase glucose uptake by tissues. 3)↓ Blood Cholesterol & phospholipids: By  cholesterol excretion in bile. 4)↑ Protein synthesis: * Normal level of thyroid hormones  normal protein synthesis. *   Thyroid hormones (in myxedema)   protein anabolism. *   Thyroid hormones (in thyrotoxicosis)   catabolic activity.

12. 2- Growth & maturation  Thyroxin is necessary for growth and maturation of most tissues through: Stimulation of protein synthesis. Acts synergistically with growth hormone & somatomedins to promote bone formation and maturation.

13. 3- Central nervous system Perinatal period: – Maturation of the CNS is absolutely dependent on thyroid hormone. – Thyroid hormones deficiency causes irreversible mental retardation. Adulthood: – Hperthyroidism causes hyperexcitability and irritability. – Hypothyroidism causes decreased mental capacity & impaired memory.

14. 4- Autonomic nervous system Has same actions as sympathetic stimulation. Up-regulate β1 adrenergic receptors in the heart (permissive action).

15. 5- Cardiovascular system  Heart rate (  Rhythmicity) due to:  O 2 consumption &  Sensitivity of SAN to adrenaline (  number of β receptors).  COP by: Direct action on heart & Potentiating chronotropic & inotropic effects of circulating catecholamine (  number & affinity of β receptors to catecholamine).  Systolic &  diastolic ABP   pulse pressure.  Peripheral resistance by VD (due to  metabolites).

17. 6- Other actions  Conversion of B-Carotenes to vitamin A. Erythropoiesis. Galactopoiesis GIT:  Motility, absorption and appetite. Respiratory system:  Pulmonary ventilation. Renal effect: Diuresis &  excretion of K +, Ca ++ & Po 4 in urine. Muscles:  Or  thyroid hormones  muscular weakness. Thyrotoxic myopathy occurs with thyrotoxicosis.

18. Regulation of thyroid hormone secretion

20. REGULATION OF THYROID SECRETION 1- Hypothalamic TRF: TRF  TSH  Thyroxin.  ↓ Thyroxin  ↑ TRF.  ↑ Thyroxin  ↓ TRF. 2- Thyrotropin (=TSH): Secreted from anterior pituitary gland under effect of hypothalamic TRF. 3- Long Acting Thyroid Stimulator (LATS): Auto-antibodies formed by lymphocytes & have similar function as TSH Stimulating thyroid gland but with long acting effect  thyrotoxicosis.

21. IMPORTANT THYROID FUNCTION TESTS 1- Serum total and free T 3 and T 4 2- Serum TSH. 3- Uptake of Radioactive iodine (I 131 ): Oral radioactive iodine is given & Determine thyroid uptake of iodine. Normal gland take = 4% in one hour. May be 25% in hyperthyroidism & 1% in hypothyroidism.

22. THYROID HORMONE RECEPTORS AND MECHANISM OF ACTION The receptors of thyroid hormones present in nuclei. Thyroid hormone-receptor complex binds to DNA   expression of specific genes  formation of mRNA  production of enzymes. Types of thyroid hormone receptors: 1- hTRα receptors: (for general metabolic function all over the body). 2- hTRβ receptors: In Brain (for development & TSH secretion).

24. THYROID HORMONE RESISTANCE Pituitary resistance: a resistance to effect of T 3 and T 4 in Brain & Pituitary due to defect in hTRβ receptors. Patients are not clinically hypothyroid (high plasma levels of T 3 and T 4 and hTRα receptors are unaffected). High non-suppressible TSH. Attention Deficit - Hyperactivity Disorder: Children who are overactive and impulsive with thyroid hormone resistance (resistance in hTRβ receptors).

25. THYROCALCITONIN Ca ++ lowering hormone, secreted by parafollicular C (Clear) cells. Polypeptide hormone with MW 3600. It is secreted due to  Ca ++ level in plasma. Action of calcitonin: 1)  plasma Ca ++ level by  mobilization of Ca ++ from bone & block action of PTH. 2)  Osteoclast activity and number (target cells). 3)  Ca ++ & P0 4 excretion in urine.

27. References  Human physiology, Lauralee Sherwood, seventh edition.  Text book physiology by Guyton &Hall,11 th edition.  Text book of physiology by Linda.S.Costanzo third edition 27

28. والأكم فطاب من طيبهن القاع *** يا خير من دفنت فى القاع أعظمه نفسي الفداء لقبر أنت ساكنه **** فيه العفاف وفيه الجود والكرم صلي الله عليه وسلم الأبيات الرائعه مكتوبه على الأعمده التى تلتصق بقبر رسول الله  