Thyroid gland Largest Endocrine organ in the body

Thyroid gland

• Largest Endocrine organ in the body • Influence the growth and development of an individual. • Involved in production, storage, and release of thyroid hormone • Function influenced by – Central axis (TRH) – Pituitary function (TSH)

Secretes hormones; 1) Thyroxine (T 4) 2) Triiodothyronine (T 3). 3) Reverse T 3 4) Calcitonin

• Thyroid gland -aggregates of follicles • Thyroid follicles –spherical in shape • Single layer of epithelial cells that surround a central thick solution called colloid • Viscous gel like substance contains thyroglobulin

ØAnother type of functional cell ØPARAFOLLICULAR CELLS Øsecrete CALCITONIN that lowers the level of calcium

Chemistry of thyroid gland Derivatives of the amino acid tyrosine bound covalently to iodine. ØThyroxine ( T 4 or 3, 5, 3', 5'tetraiodothyronine)- 95 -98% ØTriiodotyronine (T 3 or 3, 5, 3'triiodothyronine) – 2 - 5% ØRT 3 Ø T 3 is more active than T 4.

Synthesis of thyroid hormone. • • Trapping of iodide. Oxidation of iodide to iodine. Thyroglobulin synthesis Iodination of tyrosine. Coupling reaction Proteolysis of thyroglobulin Secretion of thyroid hormones

Trapping of iodide: • Secondary Active process by NIS (sodium iodide symporter). • TSH stimulates this step. Na+ K+ I-

• Thiocynate and perchlorate inhibit this iodine trapping

Oxidation of iodide to iodine : Into lumen by transporter pendrin peroxidase. II(Active form). TSH promotes this Thiouracil, thiourea, methimazole inhibit this

Thyroglobulin synthesis • • 123 tyrosine Synthesized in ER of thyroid cells Secreted into colloids by exocytosis Thyroid hormones are synthesized by thyroglobulin and remain bound to it till they are secreted.

Binding of Iodine to thyroglobulin(organification) • Iodine + tyrosine • Facilitated by thyroid peroxidase • Coupling reaction • Iodination of tyrosine: Tyrosine + I Monoiodotyrosine (MIT). MIT +I = Diiodotyrosine (DIT)

Coupling reaction: MIT+ DIT = T 3 (Triiodothyronine ) DIT + MIT= RT 3 DIT + DIT = T 4 (Tetraiodothyronine or thyroxine) Hormones are stored in the cavity of a vesicle rather than the cell itself.

Proteolysis of thyroglobulin • Endocytosis: colloid containing iodinated thyroglobulin is retrived by epithelial cells • Facilitated by megalin • Proteolysis of T 3, T 4 (colloid droplets fusing with lysosomes)

The follicular cells have 3 functions: • Collect and transport iodides into the thyroglobulin. • Synthesis of thyroglobulin. • They remove thyroid hormones from the thyroglobulin and secrete them into circulation.

Difference b/w T 3 and T 4

T 4 T 3: • Considered as the precursor of T 3. • Considered as the physiologically active form. • T 4 combines less freely with DNA receptors. • It has more affinity to the receptors on the DNA. • Amt secreted is 10 -20 times more. • Amt secreted is less. • More bound to proteins, less in free form. • Slow and sustained action. • Get metabolized slowly • Less bound to proteins and more free forms. • Fast action. • Get metabolized faster.

• T 3 and T 4 transported bound to thyroid binging globulin, thyroid binding prealbumin, albumin • Binds to nuclear receptors • T 3 binds to TR rapidly than T 4

Actions of thyroid hormones: 1. Calorigenic action : + heat production in the body Increases oxygen consumption of all metabolically active tissues except adult brain, testes, spleen, lymph node, ovary, uterus and anterior pituitary

• Increased metabolism-increase rate of heat production- thermogenic/ calorigenic action • Cellular metabolism-activated by Na+-K+ ATPase activity • Increase oxygen consumption increase the Na+-K+ ATPase activity. • In hyperthyroid BMR+80% • IN hypothyroidism-40% • Metabolism-increased by mitochondrial cytochromes-regulates the no. of respiratory unit • Oxidative phosphorylation

Effect on nervous system Essential for the normal development of the CNS. Growth of cerebral, Cerebellar cortices and basal ganglia In adult brain the hormone stimulates branching of dendrites, myelination and increase the number of synapse. Reflex time: decreases

Body growth and tissue differentiation. • GH requires thyroxine to exert its full effect on growth. • Promote expression of gene for GH • Facilitate linear growth of bones • Development of teeth • Growth of nail, hair and epidermal • Sub cutaneous tissue: Inhibits synthesis and facilitates degradation of mucopolysaccharides, hyaluronic acid • Has direct growth promoting effect on several organs. • + the production of growth hormone. • + tissue differentiation

• • • CVS: Increase oxygen consumption of cardiac muscles. Increases HR and myocardial contractility increased cardiac output Myocardial contractility is increased due to MHC expression, increased Ca 2+ and adenyl cyclase activity in cardiac muscle. Increased beta adrenergic receptors in heart Increase SBPand decrease DBP (due to vasodilation because of increase production of heat) Increases PP

Carbohydrate metabolism: • Plasma glucose level increases also there is rapid uptake of glucose by the cells, enhanced glycolysis, enhanced gluconeogenesis, glycogenolysis

Fat metabolism: • Stimulates lipolysis-increase in release free FAs and glycerol from adipose tissue • Significant decrease in plasma cholesterol due to increased excretion in bile and increases LDL receptors in liver. kidney Increased renal blood flow, GFR, increased kidney size Increased tubular reabsorption of electrolytes

Protein metabolism. Physiological dose: + structural and functional protein synthesis (anabolic). In large amt: Causes the breakdown of proteins (catabolic).

On reproductive system • Women-maturation of follicles and ovulation • Abnormalities-irregular menstrual cycle • In males –promote spermatogenesis Mammary gland: • Maintenance of milk secretion during lactation.

Vitamins: On Vit A: β carotenes are converted in to Vit A. Carotenaemia in hypothyroidism

Muscles: • In both hypo and hyperthyroidism muscular weakness is seen. • In hypo-generalized depression of metabolism. • In hyper- thyrotoxic myopathy due to breakdown of proteins.

On sympathetic nervous system • Increases expression and sensitivity of beta receptors to catecholamine.

Blood : • + erythropoiesis GIT: • + Appetite and food intake. • + Motility. • + Secretions.

Respiratory system • Increase in respiratory rate and minute ventilation

Skin: In hypo: • Coarse, dry, scaly, cold and puffy. In hyper: • Excess heat production • increase sweat production • Skin is soft , warm and wet.

Hyperthyroidism • Hyper secretion of thyroid hormones • Primary and secondary

Features: Exopthalmos-protrusion of the eye ball. Body weight decrease. Mental condition : Restless, Emotional, Anxiety, Highly irritable.

Reflex time: Decrease due to increase activity of the nervous system. Hand tremor(fine) High resting heart rate - due to stimulation of the sympathetic nervous system and release of catecholamines.

Polycythemia: Erythrocyte production increases. Hypertension : rise in systolic BP- due to sympathetic effect. Hyperphagia, hyperdefecation Low cholesterol level. Intolerance to heat. Skin : Skin soft , moist and warm-due to vasodilatation and increased sweat secretion.

Graves disease- auto immune disease All hyperthyroidism features

• Diagnosis • Estimation of T 3, T 4 and TSH in plasma • Treatment • Antithyroid drugs 1) Thionamides (inhibit 2, 3, 4) 2) the anions: perchlorate (inhibit 1) 3)High dose of iodide 4) Propranolol 5)Radioiodine

Cretinism: • Due to the deficiency of thyroid hormones in infancy.

Features: Facial : infantile features seen. Periorbital puffiness, nose broad and flattened, eyes widely placed, tongue large and protruding. Other features: Pot belly, Umbilical hernia, Sparse hair. Stature: Dwarf Mental development: Retarded, IQ is very less, myelination, branching of dentritic tree, synapse formation are affected.

Sexual: Sexually infantile, treatment becomes effective only when given before permanent changes appear. Teeth: malformed.

Myxoedema: This is due to the deficiency of thyroid hormones in adults. Causes: Iodine deficiency. Pituitary failure.

Features: Goitre: Swelling of thyroid gland. Obesity and weight gain: Solid non pitting edema-accumulation of mucopolysaccharides (myxomatous tissue)in the skin and other tissues. Face: Puffy face , typical Periorbital puffiness. Hoarseness of voice: Due to the infiltration of vocal cords with myxomatous tissue

Anemia Hypotension : due to reduced response of CVS to catecholamines. Low BMR Intolerance to cold. High cholesterol - only synthesis but destruction minimal

polymennorhoea, low sperm count in males. Somnolence and tiredness as less energy is available for normal activity. In some untreated cases severe mental deficiency occurs= Myxoedema madness.

• Goitre • Enlargement of thyroid gland –occurs both in hypothyroidism and hyperthyroidism • Goitre –in hyperthyroidism • Toxic goitre - enlargement of thyroid gland with increased secretion of thyroid hormone by thyroid tumour • Hypothyroidism Goitre • Endemic - iodine deficiency