1. Thyroid-1- TH synthesis lecture NO : 2nd MBBS
Dr. Muhammad Ramzan

2. Thyroid Gland – the background
Thyroid gland is an endocrine gland, situated at the root of the neck on either side of the trachea
It has got 2 lobes, connected in the middle by an isthmus
Thyroid derives its name from Greek word for Shield for its resemblance with Thyroid cartilage
It is also called Adams˝ Apple for laryngeal prominence

3. Thyroid gland – background cont.
It is the largest endocrine gland and highly vascular
Its size/ weight is variable in normal physiological conditions
Thyroid gland commonly weighs 20-40G

4. Thyroid gland – Sex differences
Thyroid is larger in females than males
Structure and function of thyroid gland is variable in sexual cycle, pregnancy and lactation
Diseases of thyroid gland are more common in females

5. Thyroid Gland

6. Thyroid Gland – the secretions
Thyroid functions in fetus (>11wks) and achieves its maximum activity at puberty
Thyroid gland secrets 3 hormones (TH) :
T3 and T4 from Follicular and :
Calcitonin from Para follicular cells

7. Thyroid Gland – Histology Follicular/Principal cells
Thyroid gland is composed of closed follicles and are lined with follicular/Principal (cuboidal) cells
The follicular cavity is filled with a colloid material - the Thyroglobulin - THG
Thyroglobulin is synthesized and secreted by the :
Follicular cells into the cavity

8. Histology cont. TH are synthesized within THG
Thyroid hormones (TH) are synthesized within THG
Each THG mole have 5-6 mol of TH - T4
Para follicular cells are present in B/W the follicles
They secrete Calcitonin hormone

9. Thyroid Gland- Histology

10. Thyroid gland Histology

11. Parathyroid Glands the chief cells
2 pairs of parathyroid glands are present on the posterior surface of thyroid gland
They secrete a hormone from their component cells the Chief cells, Parathormone (PTH)
PTH regulates the Ca++ and Po4 ions in the serum/ECF and activates the vitamin D

12. Parathyroid Glands

13. TH – their proportion and potency
Thyroid gland secrets 3 hormones
Tetra iodo thyronine, T4 or Thyroxin %
Triiodo Thyronine, T %
Calcitonin / Thyrocalcitonin
Potency of T3 is 10 times more than T4

14. TH – the properties free and bound forms
TH are hydrophilic and occur in free and bound form
Free TH are – FT4 and FT3
Bound forms are transported with Albumin and Globulins
T4 have more affinity for binding with plasma proteins and have delayed action >2 weeks thanT3
T3 acts more rapidly than T4 and is 10 times more active
T4 is converted first to T3 in target tissue – Deiodination

15. Biosynthesis of TH the essentials
Amino acid Tyrosine and Iodine are the 2 essentials for the synthesis of TH
Both are available in diet and are absorbed from GIT
1mg of iodide/week is required for normal synthesis of thyroid hormones (50mg/year)

16. Synthesis of TH – 5 Stages
Thyroglobulin (THG) synthesis
Iodide trapping or iodide pump
Oxidation of Iodide (for elemental iodine)
Iodination of tyrosine
Coupling Reactions

17. Thyroglobulin synthesis (THG) influenced by TSH
THG Is a large Glycoprotein, have moles of Tyrosine depending upon the type of THG
It is synthesized in the RER of the follicular cells under the influence of TSH
THG synthesis is continuous and is stored as colloid in the cavity of follicles

18. Thyroglobulin synthesis

19. Iodide trapping Iodide pump
Iodides; ingested orally, are absorbed from GIT into blood in the same manner as chlorides
1/5th of blood Iodides is actively removed by the follicular cells
This is achieved against a concentration gradient and is called Iodide trapping - Sodium Iodide symporter - NIS
The Iodine pump concentrates the iodide to about 30 – 250 times its concentration In blood when gland is active

20. Factors affecting Iodine trapping
Iodine trapping is influenced by many factors
Most important is the blood TSH level
Iodine trapping is ↑ with the ↑ in the serum TSH level
I2 is also recycled through the de iodination of the 2 TH(10%) in liver and kidneys

21. Oxidation of the Iodide ion to elemental I2
Iodide must be converted to elemental iodine for its binding with Tyrosine to form TH
Oxidation occurs inside follicular cells by an enzyme called the Thyroperoxidase (TPO)
Iodine is also present in the Follicular cells
Deficiency or absence of TPO reduces/ stops the hormone synthesis

22. Iodination of Tyrosine
Iodination of Tyrosine takes place in Follicular cavity
and TH remain part of the Thymoglobulin (THG)
THG and TH remain stored in the Follicular cavity and are sufficient for months (4 months)
Iodine is present in the Fol. cells for iodination in the cavity

23. Iodination of tyrosine – Organization occurs in follicular cavity
Iodination is the binding of Tyrosine with I2 (organization)
It takes place in the follicular cavity where THG is present ( Iodine) and :
amounts to 1/6th of the AA Tyrosine in THG

24. Iodination of Tyrosine – Organization cont. the mechanism
I2 is released from follicular cells (Exocytosis) and binds with Tyrosine with in the THG (F.Cavity) to:
Form Mono to Tetra iodo thyronine (T4)
Pendrin is the integral membranous protein (I2 Cl 2symporter) that regulates the Exocytosis of iodine
This binding is catalyzed by the enzyme Thyroperoxidase (TPO) present in the follicular cells

25. Iodination/organization of Tyrosine

26. Coupling Reactions
The Iodo tyrosine residues get coupled with one another through the coupling reactions
Coupling reactions give rise to different hormones
1mol of DIT+1mol of MIT = Tri iodo thyronine T3
2 moles of DIT = Thyroxin T4

27. Coupling Reactions cont.
1 mol of MIT+1 mol of DIT = Reverse ,rT
rT3 is 1% and is biologically inactive
MIT and DIT are not released into the blood

28. Coupling reactions

29. Storage of thyroid Hormones
TH remain as vesicles in the THG present in colloid
One mol of THG have 5- 6 moles of Thyroxin
I mol of T3 for every 10 moles of T4 in THG
Stores of TH in THG are sufficient for 4 months
As such, symptoms of TH deficiency occurs after this period - 4 months

30. Release of TH
TH are first cleaved from THG and then released in circulation
Under the influence of TSH, THG droplets are taken up by follicular cells by a process of Pinocytosis
Fusion of the droplets with Lysosomes results in the hydrolysis of THG and release of T3 and T4 in blood