Thyroid Hormone. Prof. K. Sivapalan

Thyroid Gland.2 Structure of the Gland.

Thyroid Gland.3 Structure of Thyroxine. SYNTHESISSYNTHESIS

Thyroid Gland.4 Synthesis of Thyroxine. Thyroglobulin:- two sub units, MW, 123 tyrosine molecules. Synthesized and secreted into colloid. Iodine concentrated and pushed into colloid. Tyrosine molecules iodinated to 3,5 positions- mono or di iodo thyrosines. Condensation results in tri or tetra iodo thyronines [T3- 3,5,3’, T4- 3,4,3’,4’] 3,5,5’- RT3- not active. 4 – 8 Thyroxin in one thyroglobulin molicule- storage enough for 2 months.

Thyroid Gland.5 Secretion of Thyroxine Thyroglobulin taken by endocytosis. Lysosomal digestion frees peptide bonds. T3(7%),T4 (93%) diffuse into blood. T1, T2- deiodinated. Histological differences between stimulated and resting gland.

Thyroid Gland.6 Transport of Thyroxin. Plasma level (g/dl) T4 8μg/dl T3 0.15μg/dl Thyroxin binding globulin267%46% Thyroxin binding pre albumin- transthyretin 1520%1% Albumin350013%53% Bound hormone99.98%99.8% Free hormone0.02% 2 ng/dl 0.2% 0.3 ng/dl

Thyroid Gland.7 Regulation of secretion. Thyrotrophin releasing hormone stimulates Thyroid Stimulating Hpormone which increases secretion of Thyroxine. Thyroxine inhibits TRH and TSH. [T3 may be more potent] Cold- increase and heat decresesTRH in infants not so much in adults. Stress, glucocorticoids inhibits TRH TBG elevated by estrogen and changes in free thyroxine levels influence TRH and TSH secretion.

Thyroid Gland.8 Goiter- increased TSH.

Other Goiters Thyroid Gland.9

Thyroid Gland.10 Actions of TSH It increases, Iodine uptake by the gland. Thyroglobulin, T3,T4 synthesis. Endocytosis and release of hormone. Hypertrophy and development of the gland [absence causes atrophy]. TSH and cyclical change of gland size in females.

Thyroid Gland.11 Action of Thyroxine Half life- T4- 15 days, T3 2-3 days. Latent period- T days, T hours. Most of the T4 secreted is converted to T3. T4 and T3 bind to nuclear receptors and influence production of various enzymes.

Thyroid Gland.12 Effects on Nervous System. Promotes myelination and development of synapses. Stimulates mentation- –reduced hormone results in slow mentation and –excess causes rapid mentation with irritability and restlessness. Brain development- mostly cerebral cortex, basal ganglia and cochlea. –deficiency in children causes mental retardation, rigidity and deafness. Reaction time- stretch reflex time is increased in hypothyroidism and reduced in hyperthyroidism.

Thyroid Gland.13 Relation to Catecholamines. Number and affinity of β receptor to catecholamines increased. Response to sympathetic and catecholamines are increased in hyper thyroidism.

Thyroid Gland.14 Effects on Heart. Increased ionotropic and chronotropic activities in heart. So, increased cardiac out put. Change in the type of myosin in cardiac muscle- contraction is faster.

Thyroid Gland.15 Effects on Metabolism. Protein systhesis is increased. Protein catabolism is also increased. Carbohydrate metabolism- all aspects increased. Glucose absorption and usage- increased. [quick changes in blood levels.] All aspects of fat metabolism increased, fat stores depleted. LDL and Cholesterol reduced by hepatic excretion. Increased calorie genesis- all the above and increased Na-K pump

Thyroid Gland.16 Causes of Hyperthyroidism. Hypothalamus- increased TRH [goiter] Pituitary- increased TSH [goiter] Thyroiod- –Malignancy [nodular growth] –Autoimmune disease [? goiter].

Thyroid Gland.17 Exophthalmus. Retro ocular tissues becoming more and edematous due to auto immune antibodies. Characteristic angry looking face. Increased field of vision It is associated with hyper thyroidism but can be independent also.

Thyroid Gland.18 Before and after surgical correction of exophthalmia.

Thyroid Gland.19 Effects of increased calorie genesis. Increased oxygen consumption except in, adult brain, testes, uterus, lymph nodes, spleen, and anterior pituitary. BMR increased, increased need for vitamins. Heat intolerance. Hyperphagia. Muscle wasting, increased nitrogen excretion. Reduced adipose tissue. Increased sweating, peripheral vaso dilatation. Warm, moist, soft skin [Shake hands and diagnose]

Thyroid Gland.20 Effects in nervous system Tremors- fingers, eyes. Anxiety Restlessness.

Thyroid Gland.21 Effects on CVS Tachycardia- sleeping pulse. Increased cardiac output. Increased pulse pressure.

Effects on Sexual Function Males- Impotence [lack- loss of libido] Females- Oligomenorrhoea [ lack- loss of libido, Manorrhagia, poly menorrhoea and some times amenorrhoea] Thyroid Gland.22

Thyroid Gland.23 Effects in children. Increased growth. Quick closure of epiphysis. ? Short stature.

Thyroid Gland.24 Causes of Hypothyroidism. Hypothalamus- decreased TRH [no goiter] Pituitary- [decreased TSH - no goiter] Thyroid- [increased TSH- goiter]. –Iodine deficiency. –Autoimmune disease.

Radioactive Iodine Uptake Thyroid Gland.25

Thyroid Gland.26 Effects of reduced calorie genesis. Cold intolerance. Cold, dry, scaly skin. Reduced BMR

Thyroid Gland.27 Effects of reduced Metabolism. Reduced BMR. Loss of appetite. Constipation. Loss of hair Reduced muscle power. Carotaeinaemia. Scaly skin. Myxoedema.-accumulation of muco- polysaccrides and water in inter cellular space. Husky voice- listen and diagnose.

Thyroid Gland.28 Effects of Myxoedema Non pitying oedema. Pericardial effusion. Weight gain.

Thyroid Gland.29 Moderate Myxoedema

Thyroid Gland.30 Effects in the nervous system Slow mentation. Poor memory Sleep up to 16 hours per day. Delayed ankle jerk. Muscular sluggishness. In children, defective development and severe mental retardation.

Thyroid Gland.31 Effects on CVS Slow heart. Hyper cholesterolaemia and atherosclerosis. Reduced blood volume. Low voltage ECG. Pericardial effusion.

Thyroid Gland.32 In newborn, children. Reduced growth Severe mental retardation. Cretinism

Thyroid Gland.33 Congenital Hypothyroidism- 17 years.