The thyroid gland is located in the neck below the larynx. It produces thyroid hormones including thyroxine (T4) and triiodothyronine (T3) which increase metabolism in nearly every organ system. Iodine is necessary for thyroid hormone production. Disorders include hypothyroidism, where thyroid hormone production is inadequate, and hyperthyroidism, where production is excessive. Graves' disease is an autoimmune cause of hyperthyroidism. Cretinism results from untreated congenital hypothyroidism and causes severe physical and mental impairment.

1. Thyroid Gland

2. Thyroid gland
• Largest gland in the body
• Location : in the neck inferior the larynx and
spanning over the ventral surface of trachea
• Function:
– Secretion of thyroxin and triiodothyronine
– Secretion of calcitonin

3. Thyroid Gland
 Anterior surface of the trachea
just inferior to thyroid cartilage
(or Adam’s apple)
 Two lobes connected by an
isthmus
 Microscopic thyroid follicles
produce thyroid hormone
 CCells - produce calcitonin
( Ca2+)

4. Structures and Functions of Endocrine
System
Copyright © 2011, 2007 by Mosby, Inc., an
affiliate of Elsevier Inc.
5
Fig. 48-10. Thyroid and parathyroid glands. Note the surrounding structures.

5. Thyroid Gland: Hormones and Iodine
Metabolism

7. Synthesis of Thyroid Hormone
Thyroid hormone synthesis and secretion involves processes that occur within
follicular epithelial cells and in colloid.
I-: iodide ions; I2: iodine; TG: thyroglobulin; MIT: monoiodotyrosine; DIT:
diiodotyrosine.
I-
Na+
I- I2 I2
Thyroid Peroxidase
TG
TG
MIT
+
DIT
-T3
-T4
-MIT
-DIT
-T
-T3
-M4IT
-DIT
TG
TG
+
T3
+
T4
Follicle Epithelium Colloid
Blood
Pump
Tyrosine
MIT+DIT
T3
DIT+DIT
T4

8. Releases of Thyroid Hormone

9. Synthesis of thyroid hormones
1. Iodide trapping
– By sodium iodide symporter
– Blocked by:
• Thiocyanate SCN-
• Perchlorate ClO4-
• Pertechnetate TcO4-
2. Oxidation of iodide
– By thyroid peroxidase
– Inhibited by:
3. large intake of iodide >150mcgday
4. Thioamides(refer to hyperthyroidism therapy)

10. Synthesis of thyroid hormones
3. Organification
– Tyrosine residues of thyroglobulin is iodinated
1. Inhibited by large intake of
iodide >150mcgday
2. Thioamides(refer to
hyperthyroidism therapy)
– Produce monoiodotyrosine residues MIT
and diiodotyrosine residues DIT

11. Synthesis of thyroid hormones
4. Coupling
– DIT+MIT=T3
– DIT+DIT=T4
5. Storage :
– Along with thyroglobulin
6. Exocytosis and proteolysis
– Release of T4 & T3
7. Conversion of T4 to T3 in peripheral tissue

13. T4 vs T3
T4
• Thyroid gland synthesize
90%
• 0.04%free
• Not active
• Long T12
T3
• Thyroid gland synthesize 9%
• 0.4% fr
• active

14. Mechanism of action of thyroid
hormones

15. Thyroid Gland
 Thyroid hormones target almost every body cell
Can enter cells & bind to intracellular receptors on
mitochondria & in nucleus
 Effects include:
 increased ATP production
 increased cellular metabolism, energy utilization &
oxygen consumption
 increased body temperature
growth & development of skeletal, muscular &
nervous system in fetus & children

16. Effects Of Thyroid Hormones On The
Cardiovascular System
• Increase heart rate
• Increase force of cardiac contractions
• Increase stroke volume
• Increase Cardiac output
• Up-regulate catecholamine receptors

17. Effects Of Thyroid Hormones On The
Respiratory System
• Increase resting respiratory rate
• Increase minute ventilation
• Increase ventilatory response to hypercapnia
and hypoxia

18. Effects Of The Thyroid Hormones On
The Renal System
• Increase blood flow
• Increase glomerular filtration rate

19. Effects Of The Thyroid Hormones On
Oxygen Carrying Capacity
• Increase RBC mass
• Increase oxygen dissociation from hemoglobin

20. Thyroid Hormone Actions Which
Increase Oxygen Consumption
• Increase mitochondrial Size,Number and Key
Enzymes
• Increase Plasma membrane Na-K ATPase
Activity
• Increase Futile Thermogenic Energy Cycles
• Decrease Superoxide Dimutase Activity

21. Effects Of The Thyroid Hormones On
Intermediary Metabolism
• Increase glucose absorption from the GI
tract
• Increase carbohydrate,lipid and protein
turnover
• Down-regulate insulin receptors
• Increase substrate availability

22. Effects Of The Thyroid Hormones In
Growth And Tissue Development
• Increase growth and maturation of bone
• Increase tooth development and eruption
• Increase growth and maturation of epidermis,hair
follicles and nails
• Increase rate and force of skeletal muscle
contraction
• Inhibits synthesis and increases degradation of
mucopolysaccharides in subcutaneous tissue

23. Effects Of The Thyroid Hormones On
The Nervous System
• Critical for normal CNS neuronal
development
• Enhances wakefulness and alertness
• Enhances memory and learning capacity
• Required for normal emotional tone
• Increase speed and amplitude of peripheral
nerve reflexes

24. Effects Of The Thyroid Hormones On
The Reproductive System
• Required for normal follicular development
and ovulation in the female
• Required for the normal maintenance of
pregnancy
• Required for normal spermatogenesis in
the male

25. Regulation of Thyroid Hormones

26. THYROID DISORDERS MAY BE CLASSIFIED AS:-
Hyperthyroidism (Thyrotoxicosis)
•Overproduction of Thyroid hormones
Hypothyroidism (Gland destruction)
Underproduction of Thyroid hormones

27. Hyperthyroidism

28. Hypothyroidism
Cretinism

29. .
SIGNS AND SYMPTOMS
 For Hyperthyroidism:-
• Tachycardia
• Palpitations
• Nervousness
• Tremors
• Increased BP
• Heat intolerance

30. For Hypothyroidism
• Weight gain despite poor appetite
• Cold intoleration
• Constipation
• Lethargy
• But, these symptoms are often non- specific and
makes diagnosis difficult.

31. LABORATORY EVALUATION
• Normal TSH levels practically excludes
abnormalities
• If TSH is abnormal, next steps:-
• Total and free T4 & T3 levels
• TSI( Thyroid Stimulating Ig)
• TPO(Thyroid Peroxidase Ab)
• Anti mitochondrial Ab
• Serum Tg (Thyroglobulin)
• Radioactive uptake and Thyroid scanning

32. Disease of thyroid gland
Hypothyroidism
• Hashimoto thyroiditis
(autoimmune disorder)
• Iodine deficiency
• Drugs (amiodarone)
• Radiation exposure
• Pituitary tumors
• Myxedema (life threatening
condition of
hypothyroidism)
Hyperthyroidism
• Graves disease
(autoimmune disease)
• Toxic multinodular goiter
• Drugs (amiodarone)
• Thyroid storm(life
threatening condition of
hyperthyroidism)

33. GOITER
• A goiter is a swelling of the neck or the larynx
resulting from the enlargement of the thyroid gland
( Thyromegaly ).
• Worldwide over 90 % cases of goiter are caused by
iodine deficiency.
• It may be associated with both Hypothyroidism and
Hyperthyroidism.

34. .
CLASSIFICATION OF GOITERS
 GROWTH PATTERN:-
• UNINODULAR
• MULTINODULAR
• DIFFUSE
 SIZE:-
• CLASS I
• CLASS II
• CLASS III

36.  CAUSES:
• Iodine deficiency
• Congenital hypothyroidism
• Pituitary diseases
• Thyroid cancer
• Thyroid hormone insensitivity
 TREATMENT:
• It is treated according to the cause, if thyroid gland
is producing too much T4 and T3,
• radioactive iodine is given to the patient to shrink the
gland.
• If the cause is iodine deficiency, it is supplemented
as lugol’s solution or KI

37. GRAVE’S DISEASE
• Also known as toxic diffuse goiter is an
autoimmune disease that affects the thyroid gland.
• It is the most common cause of hyperthyroidism.
• The exact cause of the disease is unclear.
• However, it is believed to involve a combination
of genetic and environmental factors.

38. SIGNS AND SYMPTOMS:
• Almost all of the signs of the disease is believed to be
a result of hyperthyroidism.
• These include insomnia, hand tremors, hyperactivity,
heat intolerance, excessive sweating, weight loss
despite increased appetite, etc.
• Exceptions are ophthalmopathy, goiter and pretibial
myxedema .

39. MECHANISM:
• Thyroid stimulating immunoglobins recognize and
bind to Thyrotropin receptor (TSH receptor) which
further stimulates the release of T3 & T4
• Thyroxine receptors in the pituitary gets activated
by surplus hormone suppressing further release of
TSH in a negative feedback loop.
• The result is very high levels of circulating thyroid
hormone and a low TSH level.

41. TREATMENT
• Treatment of graves’ disease include antithyroid drugs
which reduces the production of thyroid hormones.
• Radioiodine is also used as a measure.
Thyroidectomy(surgical excision of gland) is also
used in many cases.
• Mild cases of ophthalmopathy could be treated by
lubricant eye drops or non-steroidal anti inflammatory
drops.

42. CRETINISM
• Cretinism is a condition of severely stunted
physical and mental growth due to untreated
congenital deficiency of thyroid hormone,
usually due to maternal hypothyroidism.
 PATHOPHYSIOLOGY
• Cretinism can be endemic, genetic or sporadic.
• Poor growth is apparent as early as the first year
of life. It causes mental deterioration, swelling of
skin and loss of hair. Bone maturation and
puberty is severely delayed.
• Ovulation is impeded and infertility is common

43. CAUSE AND TREATMENT
• Most common cause is iodine deficiency.
• Populations living in areas with low soil iodine concentration
are prone to this disease.
• Sporadic and genetic cretinism results from abnormal
development or function of the fetal thyroid gland.
• This type of cretinism has been almost completely eliminated
in developed countries by early diagnosis by newborn
screening schemes followed by lifelong treatment with T4.
• Frequent monitoring (every 2–3 weeks during the first
months of life) is recommended to ensure that infants with
congenital hypothyroidism remain within the high end of
normal range.

45. MYXEDEMA
• Myxedema is a term used synonymously with severe
hypothyroidism
• Myxedema develops in the patient with almost total
lack of thyroid hormone function
• It is generally characterized by bagginess under the
eyes and swelling of the face.
• In this condition, greatly increased quantities of
hyaluronic acid and chondroitin sulfate bound with
protein form excessive tissue gel in the interstitial
spaces, and this causes the total quantity of interstitial
fluid to increase.

46. Because of the gel nature of the excess fluid, it is mainly
immobile, and the edema is the nonpitting type.
 CAUSES
• Myxedema can occur in:
• Hyperthyroidism, associated with pretibial myxedema
and exophthalmos.
• Pretibial myxedema can occur in 1–4% of patients
with Graves' disease, a cause of hyperthyroidism.
• Hypothyroidism, including Hashimoto's thyroiditis

47. PATHOPHYSIOLOGY
• Myxedema causes specific forms of dermal edema.
• The connective fibres is separated by an increased amount of
monosaccharides.
• This protein-monosaccharide complex binds water, producing
non-pitting boggy edema.
• In particular around eyes, hands, and feet.
• Myxedema is also responsible for thickening of tongue and
laryngeal and pharyngeal mucous membranes.

48. TREATMENT
1. Airway management
2. Thyroid hormone replacement
3. Gluco-corticoid therapy
4. Supportive measures

50. HASHIMOTO'S THYROIDITIS
• It is an auto-immune disease in which the thyroid gland
is gradually destroyed.
• Over time the thyroid may enlarge and form painless
goiter.
• Some people eventually develop hypothyroidism.
• After many years the thyroid shrinks in size.
• It is thought to be caused due to a combination of
genetic and environmental factors.

51. SIGNS AND SYMPTOMS
• Fatigue
• Weight gain
• Pale or puffy face
• Feeling cold
• Joint and muscle pain
• Constipation
• Dry and thinning hair
• Irregular menstrual cycles
• Depression etc

52. PATHOPHYSIOLOGY
• Various auto-antibodies may be present against
thyroid peroxidase, thyroglobulin and TSH
receptors.
• Gross morphological changes within the thyroid
are seen in the general enlargement which is far
more locally nodular and irregular than more
diffuse patterns

53. TREATMENT
• Managing hormone levels:
• Hypothyroidism caused by Hashimoto's thyroiditis is
treated with thyroid hormone replacement agents.
• E.g.: Levothyroxine, triiodothyronine.

55. Questions
1. Write a note on hyperthyroidism.
2. Write pathological changes in thyroid disorders
3. Describe the aetiology and pathophysiology of hypothyroidism
4. Explain in brief about thyroid disorders. Write about the aetiology and
pathophysiology of goitre.
5. Describe the aetiology and pathophysiology of hypothyroidism