Thyroid gland

Objectives:
1. To study the thyroid hormone secretion regarding
chemistry, control, effects and pathophysiology

2. To verify the characteristics of thyroid function tests

in common thyroid disorders

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The thyroid gland consists of an isthmus and 2 lateral

lobes, lies infront of the reck. It synthesize and secrete,
under TSH control, two thyroid Hs:-

T4: Thyroxine , 3,5,3’,5’ tetra- iodothyronine

T3: Tri-iodothyronine , 3,5,3’ – iodothyronine

These hormones are synthesized and stored as part of the

thyroglobulin with the colloidal area inside the thyroid
follicle.

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 Thyroid Hormone biosynthesis
TSH stimulates the thyroid follicle to trap
circulating iodide (I - ), and to oxidize it to iodine
( I+) by peroxidase enzyme.

Then, iodination of tyrosine occurrs, where iodine

reacts with tyrosyl residues within the
thyroglobulin.

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The 3 position of the aromatic ring is firstly iodinated and

then the 5 position to form MIT(monoiodotyrosine)
and DIT ( diiodotyrosine).

Then, there is coupling of 2 DIT molecules occur to form T4,

and 1 MIT and 1 DIT to form T3 .

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 Metabolism of Thyroid Hormones
One–half to two-third of T4 and T3 in the body is
extrathyroidal, and most of it circulate in bound form,
bound to 2 specific binding proteins:- Thyroxine-
binding globulin ( TBG) Thyroxine- binding
prealbumin ( TBPA)

Normally, TBG bind to nearly all of T4 and T3 in plasma.

The small unbound ( free) fraction is responsible for
the biological activity.

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Extrathroidal deiodination converts T4 into T3

About 80% of circulating T4 is converted into T3.

T4 contains four iodine atoms. Deiodination of T4

( by three Deiodinases) leads to production of
the potent hormone T3 ( by outer ring
deiodination by deiodinase 1 and deiodinase 2 ),
or the inactive hormone reverse T3 (rT3 ) ( by inner
ring deiodination by deiodinase 3 )

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 Thyroxine (T4)
3,5,3’,5’ -Tetraiodothyronine

Deiodinase 1 Deiodinase 3
Deiodinase 2

Tri-iodothyronine (T3) Reverse T 3 (rT3)

( 3,5,3’ – iodothyronine ) ( 3,3’,5’ – iodothyronine )

Thyroxine (T4)

T3
outer ring deiodination of T4
by deiodinase 1 and 2

rT3
inner ring deiodination of T4
by deiodinase 3
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T3 is metabolically more active and act rapidly

than T4 since T3 bind to the thyroid receptors in
the target cells with 10 times affinity compared
to T4.

For this reason, T4 is considered as a prohormone.

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 Effects of thyroid hormones
1. They regulate gene expression and tissue
differentiation.
2. They are important for general development.
3. They increase the rate of metabolism of most
body tissues, increasing oxygen consumption.
4. They enhances the function of Na+-K+- ATPase
pump.

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Systemic effects of thyroid hormones

Cardiovascular system: Increase heart rate and cardiac out.
Respiratory system: Maintain normal hypoxic and hypercapnic
drive in the respiratory center.
Gastrointestinal system: increases gut motility.
Blood: Increases red blood cell 2,3 DPG.
Bone: Increases bone turnover and resorption.
Muscle function: Increases the speed of muscle contraction and
relaxation. Increases muscle protein turnover
Sympathetic system: Increase catecholamines sensitivity.
Increase Beta-adrenergic receptors numbers in the heart, adipose
tissues, skeletal muscles. Decreases Alpha-adrenergic receptors in the
heart.
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 Effects of thyroid hormones
on
intermediary metabolism
Carbohydrate metabolsim: Increases hepatic gluconeogenesis
and glycolysis. Increases intestinal glucose absorption.
Lipid metabolsim: Increases lipolysis and cholesterol
metabolism.
Protein metabolsim: They enhances general protein synthesis and
causes positive nitrogen balance.

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Pathophysiology of the
Thyroid gland
 Goiter: Enlargement of the thyroid gland.

 The term hyperthyroidism includes only the disorders

due to an increased secretion of hormones by the thyroid
gland.

 Thyrotoxicosis: a condition of physiological and

biochemical disturbances results from exposure of body
tissues to excessive quantities of thyroid hormones.

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 Hyperthyroidism
 Hyperthyroidism is the most frequent cause of
thyrotoxicosis.
 The most common causes are Graves’ disease, toxic
multinodular goitre and autonomously
functioning thyroid nodule (toxic adenoma), and
rarely may be secondary (due to excessive TSH
secretion).

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Graves’ disease
 Graves’ disease is the most frequent cause of
hyperthyroidism, accounting for more than 70% of cases
in iodine-sufficient countries.
 Graves’ disease is caused by an autoimmune reaction to
the thyroid, leading to the production of autoantibodies
TSH receptors. These antibodies mimic TSH action in
stimulating TSH receptor on thyroid follicular cells
(TSHR-S autoantibodies).
 Since there is no feedback of thyroid hormone on the
production of TSHR autoantibodies, uncontrolled
stimulation of the receptor causes growth of the thyroid
gland and excessive production and release of thyroid
hormone, ultimately leading to hyperthyroidism.
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 Symptoms of Hyperthyroidism

Common symptoms include weight loss despite

increased appetite, breathlessness, palpitation, heat
intolerance, irritability, restlessness, nervousness,
muscle weakness, fatigue, tremor, diarrhea, sweating

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Hypothyroidism
 Deficient production of thyroid Hs.
It is usually primary, and most commonly due to
autoimmune thyroid failure. Rarely may be secondary
due to defective TSH secretion.

Symptoms of Hypothyroidism:
The classic picture includes:
weight gain, cold intolerance, fatigue, somnolence,
dry hair, dry and thick skin, deep-voiced patient
(hoarseness of voice), bradycardia , constipation, and
menorrhagia in women

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 Thyroid Function Tests

TSH measurement:- Is the most sensitive test of between

hyperthyroidism, hypothyroidism and euthyroidism.

Free T4, free T3 tests:-

These measure the unbound active hormone.

TRH test:-
To investigate the hypothalamic- pituitary dysfunction.

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Characteristics of thyroid function tests

in
common thyroid disorders
Condition TSH Free T4 Free T3
( 0.5- 4.5 µIU/ml) ( 9- 21 Pmol/L) ( 0.9-2.4 nmol/L)

Thyroxicosis (Conventional) Suppressed Increased Increased

T3 Toxicosis Suppressed Normal Increased

Secondary hyperthyroidism Increased / Increased Increased

high normal

Primary hypothyroidism Increased Low Normal / low

Secondary hyp0thyroidism Low / low normal Low Normal / low

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