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THYROID GLAND INTRODUCTION Thyroid gland is the largest gland in a normal adult. The gland weighs 15- 25g. It is a highly vascular organ. The gland is bilobed and connected by a bridge of tissue called isthmus. The function of the gland is controlled by thyroid stimulating hormone, TSH from anterior pituitary which is regulated by thyrotropin releasing hormone, TRH from hypothalamus .Thyroid hormones, T3 and T4 in circulation, provide negative feedback on secretion of TSH and TRH on anterior pituitary and hypothalamus respectively.

REGULATION OF TSH SECRETION: Hypothalamus Æ TRH Æ Anterior Pituitary Æ TSH Æ Thyroid Gland.Æ T3, T4. Factors increasing TSH secretion: 1. Anxiety 2. Excitement 3. Fall in free T3 ,T4 There exists inverse relationship between T3 T4 and TSH. Thyroid hormones regulate lipid and carbohydrate metabolism. They are important for normal body growth. Thyroid gland produces two main hormones -T3 and T4.

FORMATION OF THYROID HORMONE

1. Iodine from diet is converted to Iodide which is reabsorbed into thyroid cells by Iodide pump. 2. Iodide pump is mediated by Na+- K+ dependent ATPase system. 3. Iodide is transported into colloid and gets oxidized by thyroid peroxidase into iodine, I2. 4. I2 then gets bound to 3 position of tyrosine forming mono- iodo- tyrosine, MIT and di-iodo-tyrosine, DIT. 5. Thyroid peroxidase and coupling enzymes form T3 and T4. 6. Iodinated T3 and T4 are deiodinated by Iodotyrosine dehalogenase and secreted into circulation. DIT + DIT—-----thyroid peroxidase------Æ Thyroxine T4+ alanine MIT +DIT ------------ T3 T4 - I_ ----deiodination---------ÆT3 DIT + MIT ---------------reverse T3

TRANSPORT OF THYROID HORMONES: Thyroid hormones are transported in blood by: 1. Albumin: Highest capacity to bind thyroid hormones. 2. Thyroid binding globulin (TBG): Least capacity to bind thyroid hormones 3. Transthyretin. Free thyroid hormones are in equilibrium with protein bound thyroid hormones in plasma. Free T4 and T3 are physiologically active form. When concentration of free thyroid hormones is increased in plasma, the rate of entry of thyroid hormones in tissues is increased thereby maintaining the euthyroid state.

THYROXINE (T4) 1. Normal plasma levels: 3-8 microgms% 2. 99.9% bound to TBG. 3. Longer duration of action, but onset of action is slow 4. Free plasma levels of T4 are less than T3.

TRI IODO THYRONINE (T3). 1. 2. 3. 4.

Normal plasma levels: 0.15 microgm% 99.8% bound to TBG and albumin. Duration of action is short but onset of action is rapid. Free plasma levels are higher than T4.

ACTIONS OF THYROID HORMONES: 1. Energy Metabolism: Thyroid hormones stimulate heat production in the body, due to stimulation of O2 consumption that increases the BMR. T3 and T4 increase the O2 consumption of all tissues except brain, testes, spleen, lymph node, ovary, uterus and anterior pituitary. 2. Protein Metabolism: In physiological dose: T4 is anabolic and increases protein synthesis. IN PHARMACOLOGICAL DOSES, T4 has catabolic effect on body 3. Carbohydrate metabolism: Thyroid hormone in physiologic dose, Increase peripheral utilization of glucose, can cause hypoglycemia. Increase glucose absorption from intestine Increase glycogenesis Increase gluconeogenesis Decrease breakdown of insulin.

Thyroid hormones precipitate Diabetes Mellitus in hyperthyroid patients. 4. Lipid metabolism Increase breakdown of cholesterol in the liver Stimulate degradation of lipids. 5. Cardiovascular system: Increase in heart rate. Increase in force of myocardial contraction. Increase in systolic BP. Fall in diastolic BP. Increase in O2 consumption, leading to cardiac arrhythmias. 6. Growth and development Thyroid hormone is essential for normal body growth 7. Nervous system Thyroid hormone is necessary for normal development of nervous system. After birth, it is necessary for myelination in axons. If thyroid hormone deficiency develops before one year, it should be replaced immediately otherwise irreversible mental retardation may develop. After 2 years, if deficiency develops it can be reversed by adequate doses of T4. IN ADULTS, Deficiency causes Loss of memory, depression Slow speech Mentally lethargic 8. GIT: Essential for intestinal motility. T4 deficiency causes constipation.

HYPOTHYROIDISM CAUSES 1. Iodine deficiency in diet 2. Hashimotos thyroiditis 3. Pituitary hypothyroidism 4. Hypothalamic hypothyroidism

HYPERTHYROIDISM

1.Graves disesease 2.Toxic multinodular goiter 3. TSH secreting tumor 4. Excess intake of T3, T4.

CLINICAL FEATURES: 1. CALORIGENIC ACTION: BMR Decreases Goitre Puffiness of face Cold intolerance Weight gain Dry, thickened, rough skin.

Increases. Exophthalmos Heat intolerance Weight loss Skin: warm, moist, soft

2. CNS: Memory loss, depression. Hoarseness of voice Decreased tendon reflexes knee jerk.

Anxiety, tremors, Nervousness

3. GIT : Constipation, Anorexia

Diarrhea

4. CVS Decreased cardiac output bradycardia, pericardial effusion.

Tachycardia, High output cardiac failure, dyspnea.

5.

Menorrhagia

scanty periods

6.

Hypoglycemia

Hyperglycemia

ANTITHYROID DRUGS: 1. Inhibits trapping of Iodide- thiouracil, iodine, carbimazole . 2. Iodine or Iodide: inhibit release of thyroid hormone. 3. Beta blockers: Decrease peripheral conversion of T4 to T3. 4. Radioactive Iodine: destroy overactive thyroid tissue.

THYROID FUNCTION TESTS

HYPOTHYROIDISM

HYPERTHYROIDISM

serum T4

decrease

increase

serum TSH

Primary hypothyroidism - increase Secondary hypothyroidism - decrease

decrease

Protein Bound Iodine

decrease

Radioactive Iodine Uptake

decrease

increase

Serum Cholesterol

increase

decrease

decrease

increase

Blood Sugar

increase

MULTIPLE CHOICE QUESTIONS:

THYROID GLAND 1. One of the following does not take part in transportation of thyroid hormones in blood. a) Albumin b) Thyroid binding globulin c) Transthyretin d) Transferrin

a) b) c) d)

2. One of the following statements is not true. Anxiety increases TSH secretion. Iodide is transported into colloid and oxidised by thyroid peroxidase into iodide. Free T3 and T4 are physiologically active form. With rise of free thyroid hormones in plasma,rate of entry rate of thyroid hormones in tissues is decreased.

3. One of the following statements is false.

a) b) c) d)

T4 IS 99.9% bound to TBG. Free plasma level of T3 > T4. Duration of action of T3 >T4. Onset of action of T3 is rapid. 4. TSH is not inhibited by one of the following

a) b) c) d)

Thyroid hormones. Stress Glucocorticoids Decreased T3.

5. One of the following about thyroid hormones is false a) Thyroid hormones increase BMR. b) Thyroid hormones increase heart rate.

c) Thyroid hormones stimulate degradation of lipids. d) Thyroid hormone deficiency cause diarrhea. 6. In hypothyroidism, patients can present with: a) Puffiness of feet. b) Heat intolerance. c) Exophthalmos. d) Diarrhea. 7. In hyperthyroidism: a) b) c) d)

Tachycardia Constipation Depression Weight gain. 8. Mechanism of action of carbimazole is: a) Destroy overactive thyroid tissue. b) Inhibit release of thyroid hormones. c) Inhibit trapping of iodine d) Decreases peripheral conversion of T4 to T3.

9. Beta blockers act by a) Destroy overactive thyroid tissue. b) Inhibit release of thyroid hormones. c) Inhibit trapping of iodine d) Decreases peripheral conversion of T4 to T3. 10. one of the following is false: a) With rise in serum T4, TSH decreases. b) Serum T4 concentration decreases in hypothyroidism. c) Protein bound iodine increses in hypothyroid. d) TSH decreses in hypothyroidism. 11. One of the following is not action of thyroid hormones on CVS. a) Increase in heart rate. b) Increase in force of myocardial contraction. c) Increase in diastolic BP. d) increase in oxygen consumption.