Thyroid Hormone.

Dr. K. Sivapalan
Structure of the Gland.

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Structure of Thyroxine.
S
Y
N
T
H
E
S
I
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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- 3,5,3’,5’]
• 3,5,5’- RT3- not active.
• 4 – 8 Thyroxin in one thyroglobulin molicule- storage
enough for 2 months.

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 Transport of Thyroxin.
Plasma T4 T3
level 8μg/dl 0.15μg/dl
(mg/dl)
Thyroxin binding globulin 2 67% 46%

Thyroxin binding pre 15 20% 1%

albumin- transthyretin
Albumin 3500 13% 53%
Bound hormone 99.98% 99.8%
Free hormone 0.02% 0.2%
2 ng/dl 0.3 ng/dl
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Regulation of secretion.
• Thyrotrophin releasing hormone
stimulates Thyroid Stimulating
Hormone which increases secretion
of Thyroxine.
• Thyroxine inhibits TRH and TSH. [T3
may be more potent]
• Cold- increase and heat decreases
TRH 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.

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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
hyperthyroidism.

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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.

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 Effects on Metabolism.
• Protein synthesis 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]
• Thyroid-
• 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.

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Effects on Sexual Function
• Males- Impotence [lack- loss of libido]
• Females- Oligomenorrhoea [ lack- loss of libido, Menorrhagia, poly
menorrhea and some times amenorrhea]

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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.

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 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 mucopolysaccrides 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.

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