1. Assist prof. of Medical Physiology
Physiology of Endocrine
Abdelaziz M. Hussein
Assist prof. of Medical Physiology

2. Thyroid Gland

3. Thyroid Gland Site: Lobes: Thyroid gland is formed of 2 lobes
It is not essential for life but essential for growth and for physical and mental well-being.
Site:
On both sides of the lower aspect of the larynx and upper trachea.
Lobes:
Thyroid gland is formed of 2 lobes

4. Gross anatomy of the thyroid gland

6. Thyroid Gland Histology: Thyroid follicle is functional unit
A spherical structure lined with cuboidal cells carrying microvilli (follicular cells)
filled with ‘thyroid colloid’ containing protein called ‘thyroglobulin’.
Parafollicular cells are present between the follicles there are

7. Microscopic structure of the thyroid gland.

8. Thyroid Follicles Thyroid follicles Thyroglobulin Parafollicular
C cells

9. Functions of Thyroid Gland
Thyroid gland secrete:
Thyroid hormones:
Thyroxin or tetraiodothyronine (T4)
Triiodothyronine (T3)
Both secreted by thyroid follicular cells
Calcitonin is synthesized by the Para follicular cells
Decrease blood Ca++ level.

11. Thyroid Gland Hormones (T3 and T4)
Thyroxin or T4
Discovered first
About 90% of the thyroid output
T3 (Triiodothyronine)
Secreted in smaller amount
Have shorter half life than T4
Most active at the cellular level (3 - 5 times more active than T4)

12. 3. Iodination of tyrosine
Biosynthesis of T3 and T4
3. Iodination of tyrosine
1. Active I- uptake
2. Oxidation of I-
4. Oxidative coupling

13. Biosynthesis of T3 and T4 Blood + Lumen Follicular Cell TG TG TG TG I2
Oxidation
(Peroxidase) I2 +
10 times of plasma TG I- I- I-
Na+
Na+
Iodination
(Peroxidase)
Active transport TG T3 T3
Coupling
(Peroxidase) TG T4 T4
Diffusion
Proteolysis
Endocytosis TG

14. Biosynthesis of T3 and T4 Steps :
a) Active uptake of inorganic iodide (I-)
by an active pump.
I- is concentrated in follicular cells (> 10 times plasma level).
Stimulated by the TSH and
inhibited by thiocyanate and perchlorate (competitive inhibition).

15. Biosynthesis of T3 and T4 Steps :
b) Oxidation of I- to organic iodine (I2)
By thyroid peroxidase enzyme.
c) Iodination of tyrosine
to produce mono- and di-iodotyrosine.

17. Biosynthesis of T3 and T4 d) Oxidative coupling
Thyroxin (T4): by union of 2 diiodotyrosine molecules.
Triiodothyronine (T3): by union of monoiodotyrosine with diiodotyrosine molecule.

19. Biosynthesis of T3 and T4 Blocked by ‘thiocarbamides’
Oxidation of I-, to iodine
Iodination of tyrosine &
Oxidative coupling,
All require thyroid peroxidase enzyme.
Blocked by ‘thiocarbamides’
As thiouracil or carbimazole, decrease T3 & T4 synthesis.
Used in treatment of hyperthyroidism.

21. Storage and Release of T3 and T4
Thyroid hormones present in peptide linkage with thyroglobulin protein in the colloid.
On stimulation by TSH
Thyroglobulin is broken by a protease enzyme to release T3 and T4.

23. Iodine Requirements
1 mg /per week (for normal thyroid hormones synthesis).
Areas far from the sea, as the oases must be supplied with iodized table salt to prevent iodine deficiency.

24. Plasma level and Transport of T3 and T4

25. Plasma level and Transport of T3 and T4
In blood most of the thyroid hormones are bound to plasma proteins.
Normal plasma level:
T4 level is 8 mcg/dl,
of which 99.98% is bound and only 0.02% is free.
T3 level is 0.15 mcg%
and 99.8% of it is bound while 0.2% is free.
T3 has a shorter plasma half-life (less bound)

26. Plasma level and Transport of T3 and T4
Transport proteins are:
a) Thyroxin Binding Globulin’ or TBG (α globulin):
Carry about 50% of the hormones.
b) Pre albumin (migrating ahead of albumins in electrophoresis)
called ‘Thyroxin Binding Prealbumin’ TBPA, or Transthyretin.
transports about 40%.
c) Plasma albumin
Carry the remaining 10%.

27. Functions of T3 and T4 A. Intracellular actions (mechanism of action)
B. On the whole body produce:
1) Growth and development
2) Energy metabolism
3) GIT.
4) CVS.
5) Respiratory system.
6) Gonads and other endocrine systems.
7) Skeletal muscles.
8) Vitamins and drugs.
9) Carbohydrate metabolism.
10) Protein metabolism.
11) Fat metabolism.
12) Haemopoietic system.

28. Intracellular action of T3 and T4
T3 and T4 enter the cell by diffusion:
a) Bind to a specific nuclear receptor protein.
HRC direct transcription of specific mRNA & specific protein synthesis.

30. Intracellular action of T3 and T4
T3 and T4 Increase:
b) number and size of mitochondria & rate of cell respiration.
c) activity and number of cell membrane Na+-K+ Pump.
d) amino acid transport across the cell membrane & protein synthesis.
e) Activate proteolytic and lysosomal enzymes especially in muscles.

31. Functions of T3 and T4 on whole Body
1) Growth and development:
Thyroid hormones stimulate physical, mental and sexual growth.
Act with GH to achieve proper growth of the body.

32. Functions of T3 and T4 on whole Body
a) Physical growth:
Has a synergistic effect on GH & potentiate the effect of somatomedins.
development & Eruption of teeth.
Closure of fontanels.

33. Functions of T3 and T4 on whole Body
b) Mental growth:
Growth, development & function of CNS during fetal life & 1st few years.
Myelination of nerve fibers & development of synapses.
c) Sexual growth:
Essential for maturation & fertility.
Help milk secretion during lactation.

34. Functions of T3 and T4 on whole Body
2) Energy metabolism:
Stimulate
BMR, & O2 consumption,
heat production, and glucose uptake by cells.
Increase Heat production by accelerating the catabolic metabolism of cells.
1 mg of thyroxin increase heat production by about 1000 calories.

35. Functions of T3 and T4 on whole Body
3) Gastro-intestinal tract:
Enhance glucose absorption from the intestine and glycogenolysis.
Increase appetite and GIT motility.

36. Functions of T3 and T4 on whole Body
4) Cardio-vascular system:
Increase in HR and SV.
Systolic BP is elevated,
Diastolic BP remains normal or lowered (VD of the peripheral arterioles → reduce PR)

37. Functions of T3 and T4 on whole Body
5) Respiratory system:
Increase pulmonary ventilation.
Increase respiratory effort and increase the rate and depth of breathing

38. Functions of T3 and T4 on whole Body
6) Skeletal muscles:
Required for Normal skeletal muscle function.
Muscle weakness occurs both in hyper- and hypothyroidism;
In hyperthyroidism is due to excessive catabolism of muscle proteins.

39. Functions of T3 and T4 on whole Body
7) Gonads and other endocrine systems:
Normal hyroid hormones level required for proper sexual functions.
Both hyper and hypothyroidism lead to infertility in males and females.
Decrease the metabolic clearance of oestogen and testosterone as they Increase the synthesis of SHBG.
Increase metabolic clearance of glucocorticoids by the liver and increase ACTH release from the ant pituitary.
Potentiate the action of most of other hormones.

40. Functions of T3 and T4 on whole Body
8) Vitamins and drugs:
Increase the synthesis of vitamin A from carotenes in the liver.
Stimulate the utilization and clearance of all vitamins.
Enhance the clearance of number of drugs as digitalis.
Vitamin A

41. Functions of T3 and T4 on whole Body
9) Carbohydrate metabolism.
In physiologic amounts,
Potentiate the action of insulin &
promote glycogenesis and glucose utilization.
In large doses, induce hyperglycemia by:
Increase
1) the glycogenolytic effect of epinephrine, leading to glycogen depletion.
2) gluconeogenesis.
3) intestinal glucose absorption.

42. Functions of T3 and T4 on whole Body
10) Protein metabolism.
In physiologic amounts: have protein anabolic effect,
In large doses: increase protein catabolism.
11) Fat metabolism.
Stimulate all aspects of lipid metabolism:
synthesis, mobilization and utilization.
Decrease the blood level of:
cholesterol, triglycerides, and phospholipids.
Increase the plasma free fatty acids and glycerol.

43. Functions of T3 and T4 on whole Body
12) Haemopoietic system.
Stimulate erythropoiesis through stimulation of erythropoietin production (increase O2 carrying capacity of the blood).
Increase the amount of 2,3 DPG in the RBCs.
So, facilitate the dissociation of O2 from Hb.

44. Functions of T3 and T4 on whole Body
NB:
There is (synergism) interaction between thyroid hormones and catecholamines.
B adrenergic blockade,
is effective in decreasing cardiovascular and CNS manifestations of hyperthyroidism.

45. Thank You

46. Control of thyroid gland:
The thyroid gland activity is regulated by:
1. Plasma level of TSH.
2. Thyroid stimulating immunoglobulin (TSI),
3. Stress conditions: enhance thyroid activity
4. Age: tends to be decrease activity with increasing age.
5. Pregnancy:
6. Antithyroid agents (Goitrogens):
7. Blood iodine level

47. Control of thyroid function:
1. Thyroid stimulating hormone (TSH).
TSH has the following effects on the thyroid gland:
a) Promote hyperplasia of the follicular cells.
b) Increase iodide uptake of from the blood.
c) Stimulates synthesis & release of T3 & T4.

50. Control of thyroid function:
1. Thyroid stimulating hormone (TSH).
There is a negative feedback between thyroid hormones and TSH secretion.
Excess T3 and/or T4 suppresses the release of TSH:
by acting on the thyrotrop cells, more than on the anterior hypothalamus (site of release of TRH).
The feedback mechanism controlling thyroid gland activity act mainly on the ant pituitary.

51. Hypothalamic control of thyroid gland.

52. - - Negative feedback TRH TSH T3 & T4 Hypothalamus Pituitary g.
Thyroid g.
T3 & T4

54. Control of thyroid function:
2. Thyroid stimulating immunoglobulin (TSI),
known as ‘long acting thyroid stimulator’ (LATS).
produced by lymphocytes in all cases of Grave’s disease (autoimmune disorder leads to hyperthyroidism).
TSI acts on the thyroid similar to TSH
but
there is no –ve feed back to increased T3 and T4.

55. Control of thyroid function:
3. Stress conditions enhance thyroid activity:
e.g.
Exposure to cold
Increase the thyroid activity:
that increase BMR and heat production to
counteract the effects of low temperature.

56. 3.All types of stress
e.g exposure to cold environment stimulates the thyroid with consequent increase in metabolic rate and heat production to counteract the effects of low temperature.

57. Control of thyroid function:
4. Age:
Thyroid activity tends to decrease with increasing age. But this effect is small.
5. Pregnancy:
Thyroid activity increase during pregnancy.
The placenta secretes HCG which is structurally similar to TSH. (physiological goiter).

58. 4.Age:
Although its effect is small, but there tends to be a decrease in activity with increasing age.

59. 5-Pregnancy -Thyroid activity increases during pregnancy.
-The placenta secretes a hormone called ‘human chorionic gonadotropin’ or hCG which is structurally similar to TSH.

60. Control of thyroid function:
6. Antithyroid agents (Goitrogens):
Primary goitrogens include thiocyanates:
found in cabbage that inhibit I- uptake.
Interfere with T3 and T4 synthesis.
T4 & T3 level leads to TSH level which results in enlargement of the thyroid gland (goiter).

61. Control of thyroid function:
7. Blood iodine level:
a) Iodine deficiency: decreased T3 & T4 formation TSH  goiter.
b) Excess iodine (Wolff– Chaikoff) results in:
1- Decrease in organic binding of iodine in the gland.
2- Inhibition of TSH effect on the gland by ↓ cAMP response to it.
3- Decreased proteolysis of thyroglobulin.

62. Disorders of the thyroid gland

63. Disorders of the thyroid gland
1. Hypofunction (Hypothyroidism)
may be
Primary (thyroid defect) or
Secondary (defect in the pituitary gland).
Manifestations vary according to the age:
1. Cretinism: Hypothyroidism in human infants.
2. Myxoedema: Hypothyroidism of human adults.

64. 1. Cretinism Hypothyroidism in infants. Clinical features
May not recognized until 5-6 months after birth,
Some thyroid hormones reach the infant through milk from his mother.
Clinical features
a) Growth Retardation: physical , mental & sexual. The cretin is dwarf.
b) Low BMR and O2 consumption.

66. Clinical features of Cretinism
c) The skin is:
yellowish, scaly and
scanty coarse hair, due to failure of formation of vitamin A in the liver from carotins.
The resulting carotinaemia gives the yellowish skin.

67. Clinical features of Cretinism
c) The skin: yellowish, scaly and scanty coarse hairs.
d) Facial features:
Dull, uninterested expression and puffy eye lids.
Thick protruded tongue (macroglossia).

68. Infantile hypothyroidism

69. Clinical features of Cretinism
a) Growth Retardation.
b) Low BMR.
c) The skin: yellowish, scaly and scanty coarse hairs.
d) Facial features: Dull, puffy eye lids. macroglossia).
e) Abdomen is protuberant (potbelly) and umbilical hernia.

70. Critinism: puffy eyelids, depressed nose,
disproportionate dwarfism

71. Treatment Should be started as early as possible
by giving thyroid hormones,
because mental retardation, once developed, is irreversible.

72. 2. Myxoedema: Characterized by:
- Hypothyroidism in adults
Characterized by:
a) Retardation of all mental functions e.g.
lack of concentration, slow thinking,
long reflex time and sleepiness.
b) Low BMR & O2 consumption leads to:
- Weight gain.
- Increased sensitivity to cold weather.
c) Bradycardia & hypotension.

73. Myxoedema: puffy face, generalized fatigued appearance

75. 2. Myxoedema: d) Skin changes: Thick doughy Skin: due to
deposition of myxoedematus tissue in SC.
Pale Skin due to:
iron deficiency anaemia and
compression of cutaneous BV by the deposited SC myxoedematus tissue.
Yellowish due to carotinaemia.
Cold due to decreased BMR.
Dry scaly & brittle hair (vitamin A deficiency).

76. d) Skin changes 1- Thick Skin due to (myxoedematus tissue).
2-Skin looks pale due to iron deficiency anaemia.

77. 3- It looks yellowish due to carotinaemia.
4- It is cold due to decreased BMR.
5- dry scaly with brittle hair due to vitamin A deficiency.

78. 2. Myxoedema: f) Failure of sexual functions e.g.
Impotence in the male and
Menstrual disturbances in the female, mainly oligomenorrhea.
e) Increased level of cholesterol & triglycerides.
Treatment by giving thyroid hormones.

79. Hyperthyroidism or Thyrotoxicosis

80. II. Hyperfunction of the thyroid gland
Hyperthyroidism or thyrotoxicosis:
Due to
thyroid tumour or
over stimulation of the thyroid by TSH or TSI.

81. Hyperthyroidism or thyrotoxicosis
Clinical features
a) Excessive nervousness and irritability with insomnia and tremors of hands.
b) Loss of weight inspite of Increased appetite .
Increased catabolism of tissue proteins and oxidation of the stored fat
c) Warm moist skin, and Fine silky hair.

82. Hyperthyroidism or thyrotoxicosis
Clinical features
d) Low serum cholesterol level.
e) Increased BMR and O2 consumption
Body temp is not raised as the extra heat is lost by excess sweating.
Hot intolerance and prefer cold weather.

83. Hyperthyroidism or thyrotoxicosis
f) Ocular signs include:
Sympathetic overstimulation.
1) Characteristic stare look.
2) Infrequent blinking.
3) Lid lag phenomenon.
4) Failure of convergence.
5) Exophthalmos (protrusion of eye balls) as a result of :
‘exophthalmos producing factor’ a degradation product of TSH.
accumulation of fat, water and inflammatory cells in the retroorbital tissue and extra ocular muscles.

84. 1-Characteristic stare due to upward retraction of upper eye lid.
Ocular signs include
1-Characteristic stare due to upward retraction of upper eye lid.

85. 2-Lid lag phenomenon i.e a delay in the downward movement of the upper eye lid on following a falling object.
3-Failure of convergence.

86. Exophthalmos
5- Infrequent blinking.

87. Hyperthyroidism or thyrotoxicosis
g) Tachycardia, atrial arrythmias (as AF) and
high systolic pressure.
The diastolic pressure is not raised due to peripheral VD.
So There is high pulse pressure.

88. Hyperthyroidism or thyrotoxicosis
h) Rapid muscular fatigue due to reduced ATP synthesis.
i) Sexual disturbances
Impotence in males and
Menstrual disturbances in the female.
polymenorrhea or
menorrhagia

91. II. Manifestations of Hyperthyroidism
1) Nervousness and irritability, insomnia and tremors of hands.
2) Loss of weight inspite of Increased appetite.
3) Warm moist skin, and Fine silky hair.
4) Increased BMR and O2 consumption
5) Low serum cholesterol level.
6) Ocular signs include:
Staring look, & Infrequent blinking.
Lid lag phenomenon & Failure of convergence.
Exophthalmos

92. II. Manifestations of Hyperthyroidism
7) Tachycardia, arrythmias (as AF) and Systolic HTN, high pulse pressure.
8) Rapid muscular fatigue.
9) Sexual disturbances
In males: impotence and
In the female: Frequent menses (polymenorrhea) and (menorrhagia).

93. Goiter

95. Goiter Means: enlargement of the thyroid gland. Causes 1. Goitrogens:
It is accompanied by either hypo, or hyperfunction.
Causes
1. Goitrogens:
Substances that block synthesis of thyroid hormones,
e.g. thiocyanates and thiocarbamides.
They lead to  T3 & T4   TSH  gland size.
2. Iodine deficiency
  T3 & T4   TSH  goiter.
Called colloid goiter, the acini distended with colloid.

96. Causes of Goiter 3. Grave’s disease:
due to TSI which binds to TSH receptors on thyroid cells  diffuse goiter.
4. Nodular goiter:
Irregular enlargement of the thyroid with varying numbers of discrete nodules,
due to exposure to stresses.
5. Physiological goiter
Sometimes noticed in adolescence and during pregnancy.

97. Goiter: (enlargement of the thyroid gland)

98. Thank You