thyroid hormone
DESCRIPTION
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. - PowerPoint PPT PresentationTRANSCRIPT
Thyroid Hormone.
Prof. K. Sivapalan
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Structure of the Gland.
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Structure of Thyroxine.S
Y
N
T
H
E
S
I
S
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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.
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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.
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Transport of Thyroxin.Plasma
level (g/dl)
T4 8μg/dl
T3 0.15μg/dl
Thyroxin binding globulin 2 67% 46%
Thyroxin binding pre albumin- transthyretin
15 20% 1%
Albumin 3500 13% 53%
Bound hormone 99.98% 99.8%
Free hormone 0.02% 2 ng/dl
0.2% 0.3 ng/dl
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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.
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Goiter- increased TSH.
Other Goiters
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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.
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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.
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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.
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Relation to Catecholamines.
• Number and affinity of β receptor to catecholamines increased.
• Response to sympathetic and catecholamines are increased in hyper thyroidism.
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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.• In crease in α Myosin Heavy Chain [α
MHC] in Hyperthyroidism and β MHC in Hypothyroidism.
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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
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Causes of Hyperthyroidism.
• Hypothalamus- increased TRH [goiter]• Pituitary- increased TSH [goiter]• Thyroiod-
– Malignancy [nodular growth]– Autoimmune disease [? goiter].
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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.
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Before and after surgical correction of exophthalmia.
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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]
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Effects in nervous system
• Tremors- fingers, eyes.• Anxiety• Restlessness.
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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]
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Effects in children.
• Increased growth.• Quick closure of epiphysis.• ? Short stature.
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Causes of Hypothyroidism.
• Hypothalamus- decreased TRH [no goiter]• Pituitary- [decreased TSH - no goiter]• Thyroid- [increased TSH- goiter].
– Iodine deficiency.– Autoimmune disease.
Radioactive Iodine Uptake
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Effects of reduced calorie genesis.
• Cold intolerance.• Cold, dry, scaly skin.• Reduced BMR
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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.
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Effects of Myxoedema
• Non pitying oedema.• Pericardial effusion.• Weight gain.
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Moderate Myxoedema
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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.
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Effects on CVS
• Slow heart.• Hyper cholesterolaemia and atherosclerosis.• Reduced blood volume.• Low voltage ECG.• Pericardial effusion.
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In newborn, children.
• Reduced growth• Severe mental
retardation.• Cretinism
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Congenital Hypothyroidism-
• 17 years.