Is the larges endocrine gland in the body, weighing

about (20-25g)
It lies on the trachea at the anterior aspect of the neck
It consists of two lobes connected by a bridge of
tissue, the thyroid isthmus

Microscopic structure
Packed sacs called acini or follicles
Wall of follicles is single layer and filled with colloid
Cells columnar when active
Cells cuboidal or flat when inactive

The type of protein in the colloid is known as the

thyroglobulin

11/09/16 13:57

Department of Physiology

The primary hormones secreted by the thyroid are :

Thyroxine (T4)
Triiodothyronine (T3).
- (Reverse tri-iodothyronine, RT3)
Calcitonin

 T3 is more active than T4

Each hormone is synthesized from 2 molecules of

tyrosine and 3 or 4 atoms of iodide

Thyroxine and Tri-iodothyronine

Chemical Structure:
Iodinated amino acid tyrosine.

Thyroxine and Tri-iodothyronine

T4 & T3

Synthesis and Secretion

 The I/Na symporters (NIS) pump iodide into thyroid cells

against electrochemical gradient ,co- transported with Na
TSH induces both NIS expression and retention in the
basolateral membrane
Iodide trapping also occurs in others tissues (salivary
glands, gastric mucosa, placenta, choroid plexus, &
mammary glands)

Active iodide uptake

BLOOD
I-

I-

Na-I symporter (NIS)

Thyroid peroxidase (TPO)

COLLOID

Iodine (I2)

 Iodide is converted to iodine (I2)

This is catalyzed by thyroid peroxidase
Then iodine diffuses to the colloid down its chemical
gradients

 Glycoprotein made up of two subunits

Each molecule contains 123 tyrosine residues
It is secreted into the colloid by exocytosis

 Iodine is added to the tyrosine residues in thymoglobulin

(to carbon number 3&/or5)
This gives either mono-iodo-tyrosine (MIT) or di-iodotyrosine (DIT) residues
Iodination occurs as the iodine & thyroglobulin are
transported through cell membrane towards the colloid
and it is catalyzed by thyroid peroxidase

- coupling of the iodinated tyrosine residues with the thyroglobulin

- Also catalyzed by thyroid peroxidase
- Tyrosine + Tyrosine = thyronine
- The iodine molecules are also summated as follows:
- MIT + DIT = T3
- DIT + DIT = T4
- DIT + MIT = RT3
- Uncoupled residues

 Colloid ingested by follicular cells by endocytosis

The iodinated residues are detached from thyroglobulin by
proteases enzymes giving MIT 23%, DIT 33%, T4 35%,
&T3 7%. Only trace of RT3 are found
T3, T4, RT3are released to the blood as well as the rest of
the thyroglobulin
Iodine in MIT &DIT is extracted by iodotyrosine
deiodinase enzyme for re-utilization in thyroid hormone
synthesis

 This de-iodination is an important source of iodine

deficiency of the enzyme iodotyrosine de-iodinase
results in loss of the iodine in MIT &DIT in urine

 About one third of T4 is converted to T3 by deiodinase

found in the peripheral tissues including the liver,
kidney and brain
45% is converted to RT3
Only about 13% of T3is secreted by the thyroid while
87% is formed by deiodination of T4
And 5% of circulating RT3 is secreted by the thyroid &
95% is formed by deiodination of T4

 The average normal level in the plasma:

T3 = 2.3 nmol/L T4 = 103 nmol/L
Both hormones are found in the circulation in the two
forms:
- free form ( active form)
- protein bound form (inactive form)
About 99.98% of T4 is bound to proteins whereas about
99.8% of T3 is bound

Binding proteins
Thyroxine binding globulin (TBG)
Thyroxine binding prealbumin (TBPA)
Albumin

 Alterations in the level of binding proteins result in changes in

the level of total hormone (free + protein bound fractions) however,
plasma TSH and free hormone are normal and the patient remains
euthyroid
E.g. Elevation in TBG level causes reduction in free fraction,
resulting in elevation of TSH (due to loss ve feedback mechanism)
TSH stimulates secretion of more thyroid hormones , therefore a
new equilibrium is reached where TSH and thyroid hormone
secretion return to normal (euthyroid) but the total hormone is
increased

 Factors that increase TBG :

A- pregnancy
B- contraceptive pills (containing estrogen)
Factors that decrease TBG :
A- Androgen
B- Glucocorticoids

 Drugs that inhibit binding of TBG to thyroid Hs

- Aspirin
- phenytoin

 The half-life of each hormone:

a- T3 = 1.5 days
b- T4 = 6-7 days
Sites of metabolism:
Liver (conjugated and excreted in bile)
Kidneys, and other tissues

Mechanism of Action

Thyroxine and Tri-iodothyronine

Mechanism of Action:

Thyroxin and Tri-iodothyronine enter the cell.

Most of T4 is changed to T3 in the cytoplasm.

They bind to receptors inside the nucleus.

They induce formation of mRNA

Which affect proteins synthesis

Thyroxine and Tri-iodothyronine

Control of secretion

 Stress has an inhibitory effect on TRH secretion .

Also stimulated by cold and inhibited by heat

Thyroxin and Tri-iodothyronine

T4 & T3

Functions

Thyroxin and Tri-iodothyronine

Main Functions
calorigenic and metabolic effects
growth and development
nervous system development and function

Calorigenesis
Increase rate of heat production
Increased rate of oxygen utilization by tissues
Exceptions are adult brain, pituitary, spleen and testis.

Effect on CHO
1- Increase absorption of CHO.
2- Modulates glycogenolytic & hyperglycaemic
effects of epinephrine by increasing the
responsiveness of adenylate cyclase-cyclic AMP
system.

Effect on Protein
Stimulates protein synthesis
Stimulates protein catabolism
So the effect depends on dose and metabolic state of the individual.
* Moderate doses increase synthesis.

* Large doses increase catabolism. If food intake is not increased,

endogenous protein and fat stores are catabolised which result in
muscle weakness and weight loss.

Effect on Lipid
Stimulates all aspects of lipid metabolism
- synthesis
- mobilization
- deposition

*In general degradation is affected more and fat is

utilized for energy
Effect on Cholesterol
It decreases plasma cholesterol level

of receptors for LDL.

due to increase in number

Effect on Vitamins
It increases the demand for vitamins.
Synthesis, of vitamin A from carotene require
thyroid hormone

Effect On Growth And Development

T3 & T4 are essential for the growth and skeletal
maturation.
In hypothyroid infants : bone growth slowed and
epiphyseal closure is delayed.

Growth hormone secretion is decreased in the absence

of T3 & T4.
Thyroid hormone potentiates the effect of growth
hormone on tissues.

Effect on CNS
The effect on brain development in:
1. infants: In hypothyroidism synapses develops abnormally,
myelination is defective and mental development is retarded.
2. adults:Hypothyroidism

slow mentation

Hyperthyroidism
anxiety
The mechanism may be through potentiationg the
action of catecholamines.

Effect on C.V.S.
T3 and T4 increase the number and affinity
of B- receptor in the heart so it :
-Increase heart rate.
-Increase force of contraction of cardiac muscle.
-Increase Cardiac output.
This leads to:

Increase in Systolic blood pressure

Effects on C.V.S
Decreased peripheral resistance due to:
Vasodilatation in skin to increase heat loss.
Vasodilatation at tissues due to increase in
metabolism
This leads to:

Decrease in diastolic blood pressure

Effect on GIT
Increase the appetite
Increase motility of GIT
This leads to:

increase in frequency of bowl movement.

Diarrhoea in hyperthyroidism

Constipation is hypothyroidism.

Other actions
Necessary for normal menstrual cycles and
fertility

Abnormalities

Thyroid Abnormalities
1) Enlargement of the thyroid goiter.
2) Hyper-secretion.
3) Hypo-secretion.

 Swelling of the thyroid gland is caused by high TSH

High TSH is caused by :
Iodine deficiency (endemic goiter)
Congenital absence of thyroid enzymes

Manifestation of Thyrotoxicosis
Metabolism:
Increased heat production.
increased BMR.
heat intolerance and slight increase in body
temperature.
increased appetite.

Manifestation of Throtoxicosis

Metabolism:
Increased absorption of carbohydrate and
decreased liver glycogen.

Manifestation of Throtoxicosis

Metabolism:
decreased triglyceride and cholesterol
and increased free fatty acids.

Manifestation of Thyrotoxicosis

Metabolism:
Increase in both synthesis and degradation of
proteins but degradation more. This leads to
muscle weakness and weight loss.

Cardiovascular System
Cardiac output is increased due to:
Increase in stroke volume as a result of :
Increased contractility of cardiac muscles
Increase in heart rate.

Cardiovascular System
Peripheral resistance is decreased due to vasodilatation (to
dissipate the excess heat produced).

Cardiovascular System
In patients this is manifested as:
Tachycardia, Palpitations
Increase in systolic pressure,
Decrease in diastolic pressure,
Increase in pulse pressure
Cardiac arrhythmias.

Musculoskeletal System
MUSCLES:
Weakness and fatigability
Wasting specially proximal muscles of the limbs (thyrotoxic
myopathy).

BONES:
Demineralization with increased excretion of phosphate and
calcium in urine.
Loss of protein matrix leading to

osteoporosis.

Gastrointestinal Tract
Increase in appetite but in severe cases anorexia may be
present.
Increased gastric emptying and intestinal motility
hepatic dysfunction may occur in severe cases

Reproductive System

In childhood: Delayed sexual maturity

In adults:
Loss of libido, impotence
menstrual disturbances.

Respiratory System
Dyspnoea may occur due to
heart failure
decreased vital capacity, due to weak respiratory
muscles

Skin
Warm moist skin due to Cutaneous vasodilatation
and sweating. This occurs as a result of the
increase in metabolic rate.
Fine friable hair
Soft friable nails.

Nervous System
Nervousness
Fine tremors
Hyper-reflexia

Ocular
Exophthalmus
Lid lag and retraction

Hypothyroidism
Manifestation of hypothyroidism in infants.

Manifestation of hypothyroidism
In infants :
lead to cretinism
Short stature
Mental retardation
Rough features
Large tongue
Protruding abdomen and umbilical hernia

Hypothyroidism and Cretinism

Hypothyroidism
Manifestation of hypothyroidism in adults:

Manifestation of hypothyroidism
In adults :

myxedema
Swelling of the face
Non pitting oedema due to accumulation of hyaluronic
acid and chondroitin sulphate leading to fluid retention
Harsh voice

Manifestation of hypothyroidism
In adults :
fatigue
Intolerance to cold
Bradycardia
Constipation
Mental dullness
Rough dry skin
Loss of hair
Arteriosclerosis
Menstrual disturbances

Thyroid Function Test

General tests:
BMR (-10% to +10%).
Low in hypothyroidism high in hyperthyroidism

Thyroid Function Test

General tests:
Plasma Cholesterol Level.
High in hypothyroidism.

Thyroid Function Test

Specific Tests:
1-Plasma Hormones Measurements:
- T3 and T4 and TSH estimation.
- The response of TSH to TRH.

Thyroid Function Test

2- Radio-active iodine uptake:
2h (2-10% of dose)
6h (4-20% of dose)
24 (6-33% of dose)
Increased in hyper-thyroidisim. Decreased in hypothyroidisim

Thyroid Function Test

3-Thyroid Scan:
- Localization of sites and intensity of
radioactivity in thyroid gland.

A 35 year female patient presented to the endocrinology clinic complaining of

palpitation, loss of weight though she was eating normally, nervousness and
irregularity in her menstrual cycle.
After investigations she was diagnosed as a case of Grave's disease
(i) In this patients investigations the following findings are expected (select the right word)
a. T4 level

(increased, decreased)..

b. T3 level

(increased, decreased)..

c. TSH level

(increased, decreased) .

(ii) Explain the patho-physiology of the following symptoms

a. palpitation..
b. loss of weight.
c. nervousness