Thyroid hormone. Functional anatomy of thyroid gland

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1 Thyroid hormone ส ว ฒณ ค ปต ว ฒ ต กจ ฑาธ ช ห อง 101 Aims Functional anatomy of thyroid gland Synthesis, secretion and metabolism of the thyroid hormones The mechanism of thyroid hormone action Role of thyroid hormone in development, growth and metabolism Thyroid hormone deficiency and excess in adult 1

2 Anatomy Relation of Thyroid gland Cross section of Thyroid gland Thyroid follicle C cell Thyroglobulin store in colloid of follicle Follicle cells 2

3 Thyroid gland contains numerous follicles Colloid is composed of thyroglobulin Thyroid follicle produce and secrete thyroxine (T4) and triiodothyronine (T3) C cell or parafollicular cell produce calcitonin Synthesis of Thyroid Hormone Uptake of Iodine by thyroid Coupling of Iodine to Thyroglobulin Formation of T3, T4 from MIT / DIT Storage of MIT / DIT in follicular space Re-absorption of MIT / DIT Release of T3, T4 into serum Breakdown of T3, T4 with release of Iodine 3

4 3 Coupling T Peroxidase T Peroxidase Reabsorption COLLOID Iodination 2 T Peroxidase 4 6 Deiodinase Thyroglobulin I - 5 Lysosome 1 Iodine trap Iodine from diet I - Na + /I - symporter BLOOD VESSEL Perchlorate / excess I 2 propylthiouracil thiocyanate/ perchlorate T4 T3 propylthiouracil 4

5 Uptake of Iodine by thyroid stimulated by Thyroid stimulationg hormone(tsh) Coupling of Iodine to Thyroglobulin Monoiodotyrosine (Thyroglobulin + one I-) Diiodotyrosine (Thyroglobulin + two I-) Thyroid Hormones T4 ( THYROXINE ) T3 ( TRIIODOTHYRONINE ) Formation of T3, T4 from MIT / DIT MIT + DIT = T3 (Triiodothyronine) DIT + DIT = T4 (Thyroxine) Catalyzed by thyroid peroxidase 5

6 Majority of circulating hormone is T4 98.5% T4 1.5% T3 D = deiodinase The affinity of the receptor for T3 > T4 ~ 10 times Thyroid H. are poorly soluble in water Thyroid binding protein: thyroid binding globulin (TBG), transthyrtein and albumin Increased TBG: - High estrogen states (pregnancy,hrt) - Liver disease (early) Decreased TBG - Androgens or anabolic steroids -Liver disease total Free TSH total Free TSH Decreased binding to TBG - Phenytoin (dilantin) - Salicylates 6

7 Regulation of Thyroid Hormone Secretion Iodine uptake Colloid endocytosis Growth of thyroid gl Thyroid Hormone Action 7

8 Thyroid Hormone Action Increase basal metabolism - Stimulate cellular respiration - Stimulate cellular respiration Increase oxidative phosphorylation enzymes in cells such as cytochromes, cytochrome oxidase uncoupling proteins (UCP 1-3) Increase activity of Na + /K + pumps Increase RBC and 2,3 DPG enzyme O 2 consumption body heat production Intermediary metabolisms Lipid metabolism - Lipolysis - Cholesterol clearance Carbohydrate metabolism - Blood glucose glucose absorption from GI tract gluconeogenesis glucogenolysis 8

9 Protein metabolism protein synthesis (normal level) Na+-K+ pump, myosin ATPase activity, amount of calcium both in skeletal and heart muscle Normal muscle function High level of thyroid hormone protein breakdown Inhibit creatine kinase Growth and development Maturation and differentiation effects Stimulating GH & IGF production Bone growth and bone resorption Promote growth and development of the fetal And neonatal brain - Regulate synpatogenesis, neural integration, myelination and cell migration Increase reflex response to stimuli 9

10 Level of symphysis Normal Hypothyroid 22 years 88 years Dwarf-not hypothyroid 88 years Normal 8 years Infantile body proportion (upper > lower portion) Cretinism = dwarfism + mental retardatyion Cretinism A Color Atlas of Endocrinology p66 10

Vasodilatation Blood flow Decrease mucopolysaccharide

11 Other function Increase number and affinity of β-adrenergic receptor Heart rate, contractility & cardiac output Vasodilatation Blood flow Decrease mucopolysaccharide synthesis hypothyroid Myxedema Maintain gonadal functions Before Rx After Rx 11

12 total organification Thyroid Autoregulation Stabilize plasma T3,T4 and TSH Organic I2 I- uptake Response to TSH TSH T3, T4 not Organic I2 I 2 Organic I 2 T 3 T 4 I- uptake Response to TSH T3, T4 not Wolff-Chaikoff effect Increasing doses of I- increase hormone synthesis initially percent of I- Uptake Block Autoregulation fail Higher doses I- cause cessation of hormone formation Inorganic I- Decrease organification cause hypothyroid Dosage of stable iodide ( μg/rat) This block is temporary. 12

13 Jod-Basedow Aberration of the Wolff-Chaikoff effect Excessive iodine loads induce hyperthyroidism Thyroid Dysfunction Thyroid Dysfunction Hyperthyroidism Hypothyroidism Goitre with Euthyroid with Hyperthyroid with Hypothyroid - Puberty -Pregnancy -Graves disease - I2 deficiency -Goitrogen - Dyshormonogenesis 13

Increased metabolic rate Hyperthyroidism Weight loss, increased appetite Warm flushed skin Weak muscles that exhibit

14 Hypothyroidism Decreased metabolic rate Weight gain, reduced appetite Dry and cold skin Weak, flabby skeletal muscles, sluggish Myxedema Apathetic, somnolent Coarse hair, rough dry skin Decreased iodide uptake Possible goiter Increased metabolic rate Hyperthyroidism Weight loss, increased appetite Warm flushed skin Weak muscles that exhibit tremors Exophthalmos Hyperactivity, insomnia Soft smooth hair and skin Increased iodide uptake Almost always develops goiter 14

15 Thyroid Antibodies Destructive Ab Antithyroid peroxidase (anti TPO) Antithyroglobolin (anti TG) Hypothyroidism (Hashimoto thyroiditis) Stimulating Ab Anti-TSH receptor (TSI) Hyperthyroidism (Graves disease) 15

Thyroid Gland 甲状腺. Huiping Wang ( 王会平 ), PhD Department of Physiology Rm C541, Block C, Research Building, School of Medicine Tel:

Thyroid Gland 甲状腺. Huiping Wang ( 王会平 ), PhD Department of Physiology Rm C541, Block C, Research Building, School of Medicine Tel: Thyroid Gland 甲状腺 Huiping Wang ( 王会平 ), PhD Department of Physiology Rm C541, Block C, Research Building, School of Medicine Tel: 88208292 Outline Thyroid Hormones Types Biosynthesis Storage and Release