Thyroid Hormone. Prof. K. Sivapalan. Structure of the Gland. Structure of Thyroxine. S Y N T H E S I S. Synthesis of Thyroxine. Thyroglobulin:- two sub units, 66000 MW, 123 tyrosine molecules. Synthesized and secreted into colloid. Iodine concentrated and pushed into colloid.
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Thyroid Hormone. Prof. K. Sivapalan
Structure of the Gland. Thyroid Gland.
Structure of Thyroxine. S Y N T H E S I S Thyroid Gland.
Synthesis of Thyroxine. • Thyroglobulin:- two sub units, 66000 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.
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.
Transport of Thyroxin. Thyroid Gland.
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.
Goiter- increased TSH. Thyroid Gland.
Other Goiters Thyroid Gland.
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.
Action of Thyroxine • Half life- T4- 15 days, T3 2-3 days. • Latent period- T4- 2-3 days, T3- 6-12 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.
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.
Relation to Catecholamines. • Number and affinity of β receptor to catecholamines increased. • Response to sympathetic and catecholamines are increased in hyper thyroidism. Thyroid Gland.
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.
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.
Causes of Hyperthyroidism. • Hypothalamus- increased TRH [goiter] • Pituitary- increased TSH [goiter] • Thyroiod- • Malignancy [nodular growth] • Autoimmune disease [? goiter]. Thyroid Gland.
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.
Before and after surgical correction of exophthalmia. Thyroid Gland.
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.
Effects in nervous system • Tremors- fingers, eyes. • Anxiety • Restlessness. Thyroid Gland.
Effects on CVS • Tachycardia- sleeping pulse. • Increased cardiac output. • Increased pulse pressure. Thyroid Gland.
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.
Effects in children. • Increased growth. • Quick closure of epiphysis. • ? Short stature. Thyroid Gland.
Causes of Hypothyroidism. • Hypothalamus- decreased TRH [no goiter] • Pituitary- [decreased TSH - no goiter] • Thyroid- [increased TSH- goiter]. • Iodine deficiency. • Autoimmune disease. Thyroid Gland.
Radioactive Iodine Uptake Thyroid Gland.
Effects of reduced calorie genesis. • Cold intolerance. • Cold, dry, scaly skin. • Reduced BMR Thyroid Gland.
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.
Effects of Myxoedema • Non pitying oedema. • Pericardial effusion. • Weight gain. Thyroid Gland.
Moderate Myxoedema Thyroid Gland.
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.
Effects on CVS • Slow heart. • Hyper cholesterolaemia and atherosclerosis. • Reduced blood volume. • Low voltage ECG. • Pericardial effusion. Thyroid Gland.
In newborn, children. • Reduced growth • Severe mental retardation. • Cretinism Thyroid Gland.
Congenital Hypothyroidism- • 17 years. Thyroid Gland.