Dr siciid cawil

1. Nugaal university
Dr.siciid awil ahmed

4. Thyroid gland
 One of largest pure endocrine glands in the body
( 20gms).
 Its size depends on:
1. age … age   size.
2. sex … female > male.
3. physiological condition … (pregnancy, lactation)
 Site:
Located in the neck just below the larynx, on either
side of & anterior to the trachea.

5. Thyroid gland … (Continued)

6. Thyroid gland … (Continued)
 Thyroid gland is well vascularized (rich in blood
supply).
 Embryologically:
Originates from an envagination of the floor of
the pharynx.

7. Thyroid gland … (Continued)
 Formed of 2 lobes (Rt & Lt), that are connected by
band of tissue called “isthmus”.
 Not visible under normal conditions, but can be felt
during swallowing.

9. Thyroid gland structure - Euthyroid (normal thyroid)
1. Multiple Follicles (Acini):
 Are the functional unit.
 Thousands in no.
  100 to 300 µmeters in diameter.
 Each follicle is spherical in structure.
 Follicular wall is lined with a single layer of cuboidal
epithelioid cells that secrete into the interior of the
follicles.

10. Structure of thyroid follicle –
Euthyroid follicle
 Each follicle is filled with pink-staining proteinaceous
material called colloid.
● When the gland is INACTIVE:
colloid is abundant, follicles are large, & lining cells
are flat.
● When the gland is ACTIVE:
follicles are small, lining cells are cuboid or columnar,
& the edge of colloid is scalloped, forming many small
“reabsorption lacunae”.

11. Structure of thyroid follicle -
Euthyroid follicle
Thyroid C-cell
Basal membrane of epithelial cells
Apical membrane of epithelial cells
Cuboidal epithelial cells
Basement
membrane
Colloid
(glycoprotein)
Capillary
(Rich blood supply)

12. Structure of thyroid follicle -
Euthyroid follicle
● Each follicle is surrounded by a good & rich blood supply.
● Individual thyroid cells rest on a basal lamina that
separates them from the adjacent capillaries.
● Endothelial cells are attenuated at places, forming
gaps (fenestrations) in the walls of the capillaries.
● There are microvilli projections into the colloid from apex of
thyroid cells, & canaliculi extend into them.
● Prominent endoplasmic reticulum ( a common feature in
most glandular cells), & secretory droplets of thyroglobulins.

13. Structure of thyroid follicle -
Euthyroid follicle
2. Colloid:
Jell-like substance that contains large glycoproteins
(proteins linked by carbohydrates) called thyroglobulin,
which stores thyroid hormones within its molecules.
3. Parafollicular cells or “C-cells:
- Spherical cell, which has no relation to colloid or
cuboidal cells.
- Secrete Calcitonin, which is involved in calcium
homeostasis.

14. Thyroid gland secretions
- Secreted by Parafollicular cells.
- Important hormone for Ca2+ metabolism & homeostasis.
● 2 important thyroid hormones:
● Thyroxine (T4) or tetraiodothyronine
● Triiodothyronine (T3)
- Secreted by Follicular cells.
- Can be stored in thyroid gland for couple of months
(2-3 months).
- Having significant effect on  metabolic rate of the body.
● Calcitonin

15. Chemical nature of thyroid hormones
I
HO
COOH
CH2-CHO
 T3 has : - 2 benzene rings
- 3 iodine atoms.
- COOH & NH2 groups like an amino acid.
NH2
I
I
 T4 has : - 2 benzene rings
- 4 iodine atoms.
- COOH & NH2 groups like an amino acid.
O
I I
I
CH2-CHHO
I
COOH
NH2

16. Thyroid hormones
- Thyroxine (T4) or tetraiodothyronine …93%
- Triiodothyronine (T3) …7%
 Amount secreted:
 Almost all T4 is converted to T3 in tissues.
Target cell
T4T4
T4
Capillary
(Rich blood supply)
T3
Reverse T3

17. Thyroid hormones … (continued)
 T3 is the active form of T4.
 T3  4 times > potent (active/important) than T4 in
tissue, but it present in much smaller quantities in
blood, & persists for a much shorter time than
does T4.
 T3 has great affinity to nuclear receptors than T4.
 Reverse T3 (RT3) is inactive.

19. Transfer of thyroid hormones in blood
 Almost all THs are carried in the blood, mostly in an
inactive form, bound to 3 different types of proteins:
a. Thyroxine binding globulin … 80%
b. Thyroxine binding pre-albumin …  10%
c. Plasma albumin (serum albumin) …  10%
N.B. T4 has greater affinity to bind proteins than T3.
 Only very little T3 (0.25-0.3%) & T4 (0.03%) are carried
in the blood in the free active form.

21. Mechanism of action of
thyroid hormones
 THs are lipophilic amino acid derivative hormones.
 Their receptors are located within the nucleus of
target cells.

23. How thyroid hormones are synthesized?
 T3 & T4 are synthesized in the colloid by:
1. Iodine formation.
2. Thyroglobulin formatiom.
3. Iodination.
4. Condensation (coupling).
5. Thyroid hormones secretion.
6. Deiodination.

24. How thyroid hormones are synthesized?
1. Iodine formation:
 Iodine (Io) is a raw material essential for THs synthesis.
 Found in food, e.g. salt, & sea food, in the form of “iodide (I-)”.
 120-150 µg of I- is needed daily to maintain normal thyroid
fx in adults (or 1mg/wk).
 Iodide (I-) actively transported (trap) into the follicle (90 – 95%).
 (I-) will be 30X in thyroid cells > blood concentration.
 (I-) secreted into colloid along concentration gradient.
 Peroxidase enzyme found near apex of follicular cells.
 Peroxidase oxidize iodide (I-) to iodine (Io).

26. How thyroid hormones are synthesized?
2. Thyroglobulin formatiom:
 Thyroglobulin is a glycoprotein, made up of 2 subunits, &
has a MW of 660,000.
 Synthesized in the thyroid cells following entry aa from ECF.
 Secreted into colloid by exocytosis of granules that also
contain thyroid Peroxidase.

28. How thyroid hormones are synthesized?
3. Iodination:
 Iodine attach to tyrosine within thyroglobulin chain.
 Iodinase enzyme is found in the apical membrane 
Colloid  start iodination process.
1 Iodine + 1 tyrosine  Mono-iodo-tyrosine (MIT)
iodinase
2 Iodine + 1 tyrosine  Di-iodo-tyrosine (DIT)
Colloid

29. How thyroid hormones are synthesized?
4. Condensation (coupling):
 MIT & DIT or 2 DIT molecules coupled together.
MIT + DIT = T3
DIT + DIT = T4
N.B.
- Not all DIT & MIT  thyroid hormones.
- Only 25% of DIT & MIT give rise to thyroid hormones.
- T3 can also be formed by de-iodination (removing 1
iodine atom) of T4 by deiodinase enzyme.

30. How thyroid hormones are synthesized?
5. Thyroid hormones secretion:
 After formation of THs, they remain bound to thyroglobulin
in the colloid until secreted.
 Hormones are surrounded in colloid by acid pool, then
converted into ‘colloid droplet’.
 TSH stimulates pinocytosis of thyroglobulin into the
follicular cell.
 Lysozome enzymes hydrolyze peptide bonds & release T3
& T4 from thyroglobulin.
 T3 & T4 will be discharged freely & secreted into the
capillaries (blood), attaching to TBG.

32. How thyroid hormones are synthesized?
6. Deiodination:
 Inside follicular cells, DIT & MIT forms are NOT
secreted into the blood.
 DIT & MIT will be deiodinized to (Io) & tyrosine.
 Deiodized tyrosine will recycled back to synthesize
New MIT & DIT.

34. How thyroid hormones are synthesized?

35. Remember:
● All hormones are formed in colloid ‘lumen’.
● Colloid stores enough hormones for next 2 – 3 months.

37. Control of thyroid hormones secretions
 Hypothalamus (TRH)  Anterior pituitary gland (TSH) 
(+) thyroid gland  (+) THs via cAMP dependent mechanism.
 THs  -ve feed back mechanism to Hypothalamus inorder
to inhibit (TRH) secretion to anterior pituitary gland.

38. Control of thyroid hormones secretions
 THs  also -ve feed back mechanism to Anterior pituitary gland
in order to inhibit responsiveness to Hypothalamus (TRH).

40. Functions of thyroid hormones
 Generally, THs:
1. Increases metabolic rate.
 Stimulates increased consumption of glucose,
fatty acids and other molecules.
2. Increases metabolic heat, by  mitochondrial No &
activity   ATP,
3. Stimulates rate of cellular respiration by:
 Production of uncoupling proteins.
 Increase active transport by Na+/K+ pumps.
 Stimulates O2 consumption of most of cells in
the body.

41. Functions of thyroid hormones
4. Necessary for normal growth & maturation.
5. Promotes maturation of nervous system.
6. Stimulates protein synthesis.
7. Help regulating lipid & CHO metabolism.

43. I: Hyperthyroidism (thyrotoxicosis)
 Females > males (4:1).
 Hyperthyoidism   THs.
 Could be:
1ry hyperthyroidism … (diseases is in the gland),
e.g. Grave’s disease
Exerts TSH-like effects on thyroid.
Not affected by negative feedback.
 T3 & T4  reflex  TSH.
2ry hyperthyroidism … (disease is higher up)
 TRH   TSH   T3 & T4.
 Follicular cells become overactive.

44. I: Hyperthyroidism … ‘Grave’s disease’
 90% of hyperthyoidism is due to “Grave’s disease”.
 GD is an autoimmune disease   thyroid stimulating antibodies IgG
 Symptoms of GD:
- Exophthalmous, due to retro-orbital oedema (irreversible).
- Lid lag, due to weakness of extraoccular muscles (reversible).
- Anxiety & restlessness.
- Sleeplessness.
-  appetite,  weight & diarrhea.
- Intolerence to heat.
 Treatment:
- drugs to  iodination process, such as PTU ‘Propylthiouracil’; MMI
‘methylmercaptoimidazole’.

45. II: Hypothyroidism
Adult (Myxedema)
 Hypothyroidism in adults   THs.
 Could be:
1ry hypothyroidism … (diseases is in the gland)
- autoimmune disease such as “Hashimoto’s throiditis”.
- lack of iodine.
- absence of deiodination enzyme.
 T3 & T4  reflex  TSH.
2ry hypothyroidism … (disease is higher up)
 TRH   TSH   T3 & T4.
 Follicular cells become less active.

46. II: Hypothyroidism (myxedema) … cont.
 If No Iodine   T3 & T4   TRH   TSH
 growth (size) of the gland  simple goiter.

47. How goiter ‘swollen neck’ is formed?
With lack of iodine …
Hypothalamus
Anterior
pituitary
NO or low
feedback
inhibition
Poor
Low T3 or T4
release
 Growth of
the gland
Thyroid
gland
+
+
TRH
TSH
+++
COLD
Lack of
iodine

48. II: Hypothyroidism (myxedema) … cont.
 If there is absence of deionization enzyme 
NO recycle synthesis of DIT & MIT  accumulate.
 DIT & MIT will not be used for new THs formation
  THs.

49. II: Hypothyroidism (myxedema) … cont.
 Symptoms of Hypothyroidism:
- Decreased metabolic rate.
- Slow heart rate & pulse.
- Slow muscle contractions
-  appetite,  weight gain, & constipation.
- Prolonged sleep, & dizziness.
- Coarse skin.
- Slow thinking, lethargy, & mask face.
- Intolerence to cold ( ability to adapt cold).
- Myxoedema  swollen & puffy appearance of body,
due to deposition of protein-carbohydrate complexes
‘mucopolysaccharides’ & fluid in subcutaneous tissue.

50. II: Hypothyroidism
Children (Cretinism)
 Hypothyroidism in children  THs.
• Hypothyroid from end of 1st trimester to 6 months
postnatally, or in the 1st few years of life.
 T3 & T4  reflex  TSH.
 Additional Signs & Symptoms:
- Severe mental retardation.
- Short stature (due to  growth of bones, muscle, &
brain).
 Treatment: Thyroxine.