2. • Thyroid gland is the largest
endocrine gland in the
body(weighing about 15−25 g in
adults).
• It consists of two lobes joined
together by a narrow isthmus.
4. • Each lobule is made up
of an aggregation of
several follicles. Each
follicle is lined by
follicular cells.
5. • Follicular cells- These vary in
shape with the degree of
glandular activity. Normally (at an
average level of activity), the cells
are cuboidal and the colloid in
the follicles is moderate in
amount. During high degree of
activity, the cells become
columnar and flat when inactive.
• These cells secrete thyroid
hormones.
6. • Colloid-This is a homogeneous material that fills the
cavity of each follicle.
• The major constituent of the colloid is thyroglobulin, a
glycoprotein.
7. THYROID HORMONES
• INTRODUCTION-
• The two principal thyroid hormones include thyroxine (T4) and
triiodothyronine (T3).
• Thyroxine or T4 (3,5,3′,5′-tetraiodothyronine)- constitutes 90% of
thyroid output.
• Triiodothyronine or T3 (3,5,3′-triiodothyronine) constitutes 10%
of thyroid output; however, it is responsible for most of the tissue
actions of thyroid hormone.
• Reverse triiodothyronine (3,3′,5′-triiodothyronine) or reverse T3
or rT3 is a biologically inactive thyronine, which forms less than
1% of thyroid output.
8. • Iodine metabolism-
• Dietary intake- Iodine is essential for the synthesis of
thyroid hormones.
• Daily average intake of iodine is 500 μg.
• Daily requirement of iodine is 100−200 μg.
• Thyroid iodide- Thyroid gland contains 5−8 mg of
iodide, i.e. about 95% of total iodine content of the body.
• Thus the thyroid serves as a store of iodine.
9. • Biosynthesis and storage of thyroid hormones-
• The steps involved in the synthesis of thyroid hormones are-
1. Iodine trapping- The first step in the synthesis of thyroid
hormones is uptake of iodide by the thyroid gland, which occurs
against the chemical and electrical gradients.
10.
11. • I ̄ is absorbed into the thyroid
cell by iodide pump or Na/I ̄̄
symporter.
• It is an energy requiring process
& is linked to the ATPase-
dependent Na+-K+ pump.
12. 2. Synthesis & secretion of
thyroglobulin- thyroglobulin is a
large glycoprotein synthesized on
rough ER of the thyroid epithelial
cells. These units move to the
apical plasma membrane & release
into the lumen of the follicle.
3. Oxidation of iodide- iodide
moves to the apical surface of the
epithelial cells. From these it is
transported into the lumen of the
follicle by a transporter called
pendrin.
13. • The iodide is then immediately oxidised
to iodine by the enzyme peroxidase
• 4. Organification of thyroglobulin-
refers to the iodination of tyrosine
residues present in the thyroglobulin
molecule. This reaction occurs at the
apical membrane of the cell as soon as
the thyroglobulin molecule is released
by secretory granules by exocytosis &
requires thyroid peroxidase.
• Tyrosine is first iodinated at position 3
to form MIT and then at position 5 to
form DIT.
14. 5. Coupling reaction- two molecules of DIT
couple to form T4. One molecule of MIT when
coupled to one molecule of DIT,
triiodothyronine(T3) is produced. Enzyme
peroxidase is required for coupling.
6.Storage- once thyroglobulin has been
iodinated it is stored in the lumen of the follicle
as colloid for several months. It is estimated
that the stored thyroid hormone can meet the
body requirement for 1-2 months.
15. HORMONE SECRETION-
• Secretion of thyroid H from the colloid stored in the
lumen of the follicle involves following steps-
• Endocytosis
• Proteolysis
16. • Endocytosis- colloid containing iodinated
thyroglobulin is retrieved from the lumen of
the follicle by the epithelial cells through
endocytosis. Megalin receptor located on
the apical membrane facilitates this process.
The colloid enters the cytoplasm in the
form of colloid droplets by pinocytosis
which moves towards the basal membrane.
• Proteolysis- the colloid droplet fuses with
the lysosome vesicle containing proteolytic
enzyme. The proteases digests the
thyroglobulin molecule releasing T3, T4,
DIT and MIT.
• T3 and T4 diffuse through epithelial cells
into the blood stream.
17. • Transport of T4 and T3- secreted T4 & T3 circulate in
the blood stream in two forms:
• Bound & free-
1. Bound form- most of the circulating T4 and T3 is bound
to specific binding protein.
• Thyroxine binding globulin is the major binding protein
which binds 70% of T4 and T3.
• Thyroxine binding prealbumin binds about 15–20% of
T4.
• Thyroxine binding albumin, binds about 10% of the T4.
18. 2. Free form- Only about 0.05% of T4 and 0.5% T3
circulate unbound (free form) in the plasma.
These free, unbound hormones represent the biologically
active hormone.
19. • REGULATION OF THYROID HORMONE
SECRETION-
• The secretion of thyroid hormones is
regulated by:
• Negative feedback mechanism through
hypothalamus–anterior pituitary–thyroid gland
axis and
• Autoregulation of thyroid gland.
20. • A. Regulation through negative
feedback mechanism-
• The negative feedback
mechanism operating through
hypothalamus–anterior
pituitary–thyroid gland axis-
plays the essential role in
controlling secretion of thyroid
hormones by:
• Thyroid-stimulating hormone-
21. • Action of TSH- TSH exerts following effects on
the thyroid gland:
1. Increases the secretion of thyroid hormones by
accelerating all the steps in biosynthesis.
2. Increases the number (hyperplasia) and size
(hypertrophy) of the follicular epithelial cells.
3. Increases the vascularity of the thyroid gland.
22. • Regulation of TSH production-
The production of TSH is
regulated by the following.
• 1. Feedback control by plasma
T4 and T3- Day-to-day
secretion of TSH depends upon
the negative feedback control
exerted by the plasma levels of
free T4 and T3.
• A fall in T4 and T3 levels
stimulates TSH secretion from
the anterior pituitary, while
• A rise in T4 and T3 levels
inhibit TSH secretion.
23.
24. 2. Hypothalamic control of TSH-
• Hypothalamus exerts its effect by secreting
thyrotropin releasing hormone (TRH).
• Thyrotropin-releasing hormone-
• Secretion of TRH by the hypothalamus is
controlled by:
• Nervous stimuli like emotion, stress,
exposure to cold etc. and also by Negative
feedback control exerted by plasma T3 and
T4 levels on the hypothalamus.
25. • B. Autoregulation of thyroid gland-
• The secretions of thyroid gland are
regulated by food iodine contents.
• If there is deficiency of iodine content in the
diet then the iodine trapping mechanism of
the follicular cells becomes super efficient
and vice versa is also true, i.e. when there is
excess of iodine content in the food then
iodine trapping becomes less efficient and
organification of excess amount of iodine
does not occur.
• In this way, iodine availability for thyroxine
synthesis remains constant and this
phenomenon is called autoregulation of
26. • MECHANISM OF ACTIONS
OF THYROID HORMONE-
• The thyroid hormones do not
have any discrete target organ.
• They affect cellular activity of
almost all the tissues of the
body. T3 acts by its effect on the
gene expression on the target
cell. Overall scheme of the
thyroid hormone effects is
described
27. ACTIONS OF THYROID
HORMONE-
1. Effects on growth and tissue
development-
(i) Role in normal body growth and skeletal
maturation-
• increases synthesis of proteins and
enzymes; and indirectly by increasing
production of growth hormone and
somatomedins. Some important effects are
on:
• Bone development,
• Teeth development,
• Normal cycle of growth and maturation and
28. (ii) Role in tissue differentiation and maturation.
(iii) Role in development of nervous tissue- T3 seems to
be necessary for proper axonal and dendritic development
as well as normal myelination in the nervous system.
• This is the reason of mental retardation being a striking
feature in a child with congenital hypothyroidism.
29. 2. Effect on the metabolic rate in general-
• The thyroid hormone in general stimulates the
metabolic activities and increases the basal rate of
oxygen consumption and heat production in most
tissues of the body.
3. Effects on metabolism-
(i) Effect on carbohydrate metabolism-
• Increases peripheral utilization of glucose(insulin like
action)
• Increased glucose absorption from the GIT and
increased gluconeogenesis & glycogenolysis.
30. (ii) Effect on fat metabolism- Thyroid hormones
causes:
• Mobilization and degradation of lipids by increasing
activity of lipase.
• Plasma cholesterol level is lowered due to increased
excretion in bile.
31. (iii) Effect on protein metabolism- In
physiological amounts, the thyroid hormones
function as anabolic hormones. That is, they
cause positive nitrogen balance.
• In high concentrations, thyroid hormones
have catabolic effect leading to negative
nitrogen balance. Therefore, muscle
weakness and creatinuria are characteristic
features of a hyperthyroid patient.
32. (iv)Effect on water and electrolyte balance-Thyroid
hormones play role in the regulation of water and
electrolyte balance.
Impairment of thyroid function is associated with
retention of water and electrolytes, which can be reversed
by hormonal administration.
33. • 4. Respiratory effects
(i) Increase in the resting respiratory rate, minute
ventilation
(ii) Increase in oxygen carrying capacity of blood by
slightly increasing the red blood cells.
34. 5. Cardiovascular effects –
• Thyroid hormone increases cardiac output, ensuring sufficient
oxygen delivery in the tissues.
1. Tachycardia, i.e. increased heart rate (at rest, even during
sleep).
2. Force of cardiac contraction is increased
3. Cardiac output is increased as a result of increased blood
volume, increased heart rate and increased force of
contraction.
4. Effect on blood pressure. Systolic blood pressure is increased
5. Vasodilatation and increased blood flow to tissues
35. • 6. Effects on nervous system-
(a) Effect on development of nervous system-
• Thyroid hormones play an essential role in the development
of nervous system. Critical period for the development of
nervous system is up to 1 year of life.
• (b) Effect on functioning of nervous tissue in adults-
enhances wakefulness, alertness, responsiveness to various
stimuli, auditory sense, awareness of hunger, memory and
learning capacity.
36. 7. Effects on gastrointestinal tract-
• Effects of thyroid hormones on GIT include:
• Increase in appetite and therefore increase in food intake
• Increase in rate of secretion of digestive juices
8. Effects on reproductive system-
• In males, lack of thyroid hormones causes complete loss of
libido and excess of hormones causes impotence.
• In females, lack of thyroid has varying effects:
• Menorrhagia and polymenorrhagia or Amenorrhoea.
37. APPLIED ASPECTS OF THYROID
HORMONES-
• ABNORMALITIES OF THYROID GLAND-
• Hyperthyroidism and
• Hypothyroidism.
• Hyperthyroidism-
• Hyperthyroidism refers to increased secretion of thyroid
hormones. Its common causes are:
1. Graves’disease(exophthalmic goiter or thyrotoxicosis)
2. Toxic nodular goitre.
38. • Graves’ disease-
• Graves’ disease is the most common
cause of hyperthyroidism.
• Aetiology
• It is an autoimmune disease
characterized by the development of
thyroid-stimulating antibodies
(TSAb) against the TSH receptors,
also called long acting thyroid
stimulator. These antibodies bind to
TSH receptors and mimic TSH
action.
• The entire thyroid gland undergoes
hyperplasia as a result of
autoimmune stimulation
39. • Symptoms and signs-
1. General features include:
• Marked increase in basal metabolic rate (BMR), Weight
loss, despite an increased intake of food and Increased
heat production causes discomfort in warm
environments, excessive sweating and a greater intake of
water.
2. Goitre- Goitre refers to the swelling of thyroid gland.
Graves’ disease is characterized by diffuse goitre, while
single or more nodules indicate toxic nodular goitre.
3. Cardiovascular features are:
40. • Increased pulse rate or sinus tachycardia and
• Arrhythmias (atrial fibrillation is commonest).
4. Neuromuscular features are: nervousness, irritability,
restlessness, psychosis, tremors of hand, muscular
weakness and exaggerated tendon reflexes.
5. Gastrointestinal features are diarrhoea and vomiting.
6. Dermatological features are perspiration (increased
sweating or hyperhidrosis), loss of hair and redness of
palm.
7. Reproductive features are impotence in males and
oligomenorrhoea or amenorrhoea, abortions and
infertility in females.
41. • Investigations-
• Both T3 and T4 plasma levels are elevated.
• TSH is low or may become undetectable.
• 131I Uptake is increased.
42. • HYPOTHYROIDISM-
• Hypothyroidism is a clinical syndrome caused by low levels
of circulating thyroid hormones.
• Aetiology
• Depending upon the aetiology, hypothyroidism can be
primary or secondary.
• Primary hypothyroidism - is caused by the disorder of
thyroid gland
• Secondary hypothyroidism - is caused by diseases of
anterior pituitary and hypothalamus.
• Clinical features
• Clinical features depend upon the age at which deficiency
manifests, duration and severity of the disease.
43. • Two different clinical entities are:
• Infantile hypothyroidism (cretinism).
• Adult hypothyroidism (myxoedema).
44.
45.
46. 1. Infantile hypothyroidism (cretinism)- It occurs when thyroid
deficiency occurs during first year of life and is characterized by
mental retardation, marked retardation of growth, delayed milestones
of development, pot belly, protruding tongue, dry skin and sparse
hairs.
• Radiograph of bone shows delayed bone age-
• Treatment should be prompt otherwise mental deficiency will persist.
47. • At adolescence, hypothyroidism is
characterized by short stature, poor
performance at school, delayed puberty and
sexual maturation. Other features of adult
hypothyroidism are present to variable degree.
48. • 2. Adult hypothyroidism - is also called myxoedema because of
characteristic infiltration of skin by myxoedematous tissue.
• Symptoms and signs include:
• General features:
• Tiredness and weight gain without an appreciable increase in
caloric intake. Decreased heat production, lower body temperature,
causes intolerance to cold and decreased sweating.
49. • Cardiovascular features- bradycardia.
• Neuromuscular features- Movement, speech and thought are all
slowed and lethargy, sleepiness, delayed relaxation of ankle jerks.
• Dermatological features- Dry thick skin (toad skin), sparse hair,
non-pitting oedema due to infiltration by myxoedematous tissue
(myxoedema).
• Reproductive features- menorrhagia and infertility (common)
galactorrhoea and impotence (less common).
• Gastrointestinal features- Constipation .
• Haematological feature - includes anaemia.
50. • Investigations-
• Serum T3 and T4 levels low
• Serum TSH levels high in primary and low in
secondary hypothyroidism
51. • GOITRE-
• Goitre refers to any abnormal increase in the size of the thyroid
gland. The term goitre does not denote the functional status of
thyroid gland, because it may be associated with:
• Euthyroid,
• Hypothyroidism, and
• Hyperthyroidism,
52. • Iodine-deficiency goitre or endemic goitre
occurs when the daily dietary intake of iodine
falls below 10 μg (normal requirement
100−200 μg/day). It decreases the synthesis
and secretion of thyroid hormone leading to
increased TSH levels and proliferation of
thyroid gland tissue (goitre).
53. • if the intake of iodide exceeds 2 mg/day, the
intraglandular concentration of iodide reaches a level that
paradoxically suppresses TPO activity, blocking
hormone biosynthesis. This phenomenon is known as the
Wolff-Chaikoff effect.
• Pendred syndrome- a genetic disorder
characterized by sensorineural hearing loss and
goiter.
55. ANTI THYROID DRUGS
• Carbimazole, methimazole and
propylthiouracil are most commonly used.
• Reduce the synthesis of thyroid hormones
by inhibiting the iodination of tyrosine
residues.
56. ANTI THYROID DRUGS
• ADVANTAGE-
No surgery and no use of radioiodine.
DISADVANTAGE
Tt is prolonged and the failure rate is atleast 50%
60. HASHIMOTO THYROIDITIS-
• The treatment of choice for Hashimoto thyroiditis is
thyroid hormone replacement.
• The drug of choice is orally administered
levothyroxine sodium, usually for life.
• Indications for surgery
• A large goiter with obstructive symptoms such as
dysphagia, voice hoarseness, and stridor.
• Cosmetic reasons for unsightly large goiters
62. • For many years it was
thought that thyroid
hormones diffuse
passively across cell
membranes, but this is
now known to require
transport proteins. These
include the
monocarboxylate
transporters MCT8 and
MCT10, which are capable
of transporting both T4
and T3 across the plasma
membrane
63. • For many years it was
thought that thyroid
hormones diffuse
passively across cell
membranes, but this is
now known to require
transport proteins. These
include the
monocarboxylate
transporters MCT8 and
MCT10, which are capable
of transporting both T4
and T3 across the plasma
membrane
64. • In humans there are two thyroid
hormone receptor genes, THRA
and THRB, located on
chromosomes 17 and 3,
respectively.
• TR forms heterodimers with RXR
Unliganded TR-RXR binds to
thyroid response elements in target
genes and recruits co-repressors
that inhibit gene transcription.
Upon T3 binding, the co-repressors
are released, and coactivators are
