Thyroid Hormone

Thyroid Hormone.

Prof. K. Sivapalan

08-01-14 Thyroid Gland. 2

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.• 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.


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.


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


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.


Goiter- increased TSH.

Other Goiters



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.


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.


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.


Relation to Catecholamines.

• Number and affinity of β receptor to catecholamines increased.

• Response to sympathetic and catecholamines are increased in hyper thyroidism.


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.


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


Causes of Hyperthyroidism.

• Hypothalamus- increased TRH [goiter]• Pituitary- increased TSH [goiter]• Thyroiod-

– Malignancy [nodular growth]– Autoimmune disease [? goiter].


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.


Before and after surgical correction of exophthalmia.


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]


Effects in nervous system

• Tremors- fingers, eyes.• Anxiety• Restlessness.


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]



Effects in children.

• Increased growth.• Quick closure of epiphysis.• ? Short stature.


Causes of Hypothyroidism.

• Hypothalamus- decreased TRH [no goiter]• Pituitary- [decreased TSH - no goiter]• Thyroid- [increased TSH- goiter].

– Iodine deficiency.– Autoimmune disease.

Radioactive Iodine Uptake



Effects of reduced calorie genesis.

• Cold intolerance.• Cold, dry, scaly skin.• Reduced BMR


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.


Effects of Myxoedema

• Non pitying oedema.• Pericardial effusion.• Weight gain.


Moderate Myxoedema


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.


Effects on CVS

• Slow heart.• Hyper cholesterolaemia and atherosclerosis.• Reduced blood volume.• Low voltage ECG.• Pericardial effusion.


In newborn, children.

• Reduced growth• Severe mental

retardation.• Cretinism


Congenital Hypothyroidism-

• 17 years.

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Thyroid Hormone