The thyroid gland

Structure of the thyroid gland:

Histology of the thyroid gland:
The thyroid gland synthesizes the following hormones:
1. Thyroid hormones (T3 and T4) ----> by the follicular cells.
2. Calcitonin ----> by the parafollicular cells.

Characteristics Thyroid hormones:

a) T3 (Tri-iodothyronine)
b) T4 (Tetra-iodothyronine or thyroxine)
- T3 is about 3 to 5 times more active than T4 .
- Each hormone is synthesized from two molecules of tyrosine and 3 or
4 atoms of iodide.
thyroid hormone synthesis:
Steps:
1. Iodide trapping.
2. Synthesis of thyroglobulin.
3. Oxidation of iodide.
4. Iodination of tyrosine.
5. Coupling of T1 & T2.
6. Pinocytosis and digestion
of colloid.
7. Secretion of hormones.
8. Transport in the blood.
Thyroid hormones in the plasma:
- The average normal level in the plasma:
[T 3 ] = 2.3 nmol/L
[T 4 ] = 103 nmol/L
- Both hormones are found in the circulation in the two forms:
• Free form (the active form that carries out the functions).
• Protein bound form (inactive form not filtered in the kidney, acts as
storage form).
- About 99.98% of T4 is bound to proteins whereas about 99.8% of T3
is bound to proteins.
The binding proteins:
1. Thyroxine binding globulin (TBG)
- Has the highest affinity to bind thyroxine.
- It carries about 67% of all T4 and 46% of all T3 in plasma.

2. Thyroxine binding albumin (TBA)

- Has the highest capacity to bind thyroid hormones.
- It carries about 13% of all T4 and 53% of all T3 in plasma.

3. Thyroxine binding pre albumin (TBPA or Transthyretin)

- It carries about 20% of all T4 and 1% of all T3 in plasma.
 Effects on Growth:
- Thyroid hormones are needed for normal growth and
skeletal maturation.
- In addition, they potentiate the effects of growth hormone
on tissues.
- Promote growth and development of the brain during fetal
life and for the first few years of postnatal life.
Effect on metabolism:
 CHO:
Hyperglycemic
- Increase absorption of carbohydrates in the GIT.
- increases degradation of insulin
- potentiates the glycogenolytic effects of catecholamines
 Fat:
- increase mobilization of fat
- decrease cholesterol level in plasma.
because they increase formation of LDL receptors in the liver cells;
thus increasing hepatic uptake of cholesterol to be excreted in bile.
 Protein:
- increase protein catabolism (in high levels)
- increase protein anabolism (in low to moderate levels).
 Vitamins:
- increase the need for vitamins.
- They convert carotene to vitamin A in the liver.
* In hypothyroidism, carotene accumulates in plasma (carotenemia)
causing yellowish coloration of the skin.
 Effects on CVS:
Thyroid hormones have the following effects on the
cardiovascular system:
- Increase heart rate
because they increase number & affinity of β1 receptors to
catecholamines.
They also increase α myosin heavy chains, G proteins, Na-K
ATPase pump and some K channels.
- Increase stroke volume
- Increase the cardiac output
- Increase the systolic blood pressure
- Vasodilatation
- Decrease the diastolic blood pressure
- Increase the pulse pressure

 Effects on GIT:
- Increase appetite and increase intestinal motility.
* Hypothyroid patients suffer from constipation whereas
hyperthyroid patients suffer from diarrhea.
 Effects on CNS:
- Increase development of the brain in children (especially
the cerebral cortex, basal ganglia and cochlea).
That is why hypothyroidism in children causes mental
retardation, motor rigidity, and deafness.
- Increase mentation in adults

 Other effects:
- Increase milk synthesis.
- Essential for normal menstruation and fertility
* Therefore hypo and hyperthyroidism are associated with
abnormal menstruation.
Effects of thyroid hormones:
Thyroid hormones regulate:
1-Cellular metabolism.
2- Oxygen use and BMR.
3- Growth & development.
 Mechanism of thyroid hormone action:
 Control of secretion:
Abnormalities:
Hypothyroidism:
Causes:
1. Iodine deficiency.
2. Autoimmune thyroiditis (hashimoto‫ﹸ‬s disease)
Autoantibodies that destroy the thyroid.
3. Inflammation.
Idiopathic nontoxic colloid goiter.
4. Congenital deficiency of the enzyme system involved in
thyroid hormone synthesis.
- deficient iodid trapping
- deficient peroxidase system
- deficient coupling
- deficiency of the deiodinase enzyme
5. Tumors.
6. Antithyroid drugs.
7. Surgical removal.
 Features of hypothyroidism:
- Low metabolism = decreased heat production = intolerance to cold.
- CNS symptoms (sleepy, slow mentation and poor memory).
- Bradycardia.
- Constipation.
- Voice becomes characteristically husky and slow.
- High cholesterol level in plasma.
- Skin becomes dry and yellow (carotenemia).
- Hair changes:
- coarse and sparse.
- loss of the outer
eyebrow.
- In severe case
myxedema.
Cretinism:
Congenital hypothyroidism
Extreme hypothyroidism during fetal life, infancy, or childhood

Caused by:
- Maternal iodine or thyroid hormone deficiency
- Maternal antithyroid antibodies that cross the placenta
- Congenital absence of the thyroid gland
- Congenital absence of enzymes involved in thyroid hormone
synthesis
- In addition to the above features of hypothyroidism,
cretinism is associated with:
Physical and mental growth retardation
- Mental retardation
- Short stature
- Large protruded tongue
- Umbilical hernia.
Hyperthyroidism (thyrotoxicosis):
Primary hyperthyroidism is caused by:
- toxic tumors
- Inflammation
- Drugs
- Autoantibodies that activate the thyroid (Graves’ disease)

Secondary hyperthyroidism is caused by:

- pituitary tumors (increase production of TSH)
Features of hyperthyroidism:
- Increased metabolism = increased heat production = intolerance to
hot.
- Increased heart rate, SV, COP, systolic B.P. and pulse pressure.
Decreased diastolic B.P.
- Irritability and nervousness
- Increased appetite (hyperphagia)
- Diarrhea and weight loss
- Fine tremor
- Warm, soft skin and sweating
- Eye signs: (only in Graves’ disease).
Eye signs (only in Graves’ disease):
- Lid retraction:
retraction of the upper eyelid; allowing appearance of the whitish
sclera above the cornea.
- Lid lag:
delay in movement of the upper eyelid
when looking to an object descending
from above to downwards.
(during clinical examination).
- Exophthalmos:
protrusion of the eye globe forward
due to inflammation and edema
of the tissues in the orbit.
Goiter:
Swelling of the thyroid gland caused by high TSH.
High TSH is caused by:
- Iodine deficiency (endemic goiter)
- Anti-thyroid drugs
- Goitrogens:
chemical substances found in vegetables, converted in the
intestine to an antithyroid agent that causes goiter.
e.g
Broccoli

Cabbage
Cauliflower
* Graves’ disease
Tests assessing thyroid function:
1- Total & free T3 & T4:
by radioimmunoassay
2- TSH:
Measurement of TSH by radioimmunoassay differentiates
between primary and secondary thyroid hormone
abnormalities.