1. THYROID HORMONE:
• Gross and Microscopic Anatomy of the Thyroid Gland.
• Production of Thyroid Hormones.
• Transport of T3 and T4
• Actions of Thyroid Hormones.
• Regulation of Thyroid Hormones.
• Hyper- and Hypothyroidism
PREPARED BY:
Dr.Abdul Wahab Aslam

2. HIsTOlOgY Of THE THYROID glaND
• The thyroid gland contains numerous follicles, composed of
epithelial follicle cells and colloid.
 Also, between follicles are Para-follicular cells, which produce
Calcitonin.

3. THE THYROID glaND – HIsTOlOgY:
Squamous epithelial cells, cuboidal cells (follicle cells).
Gland is composed of hollow spheres, called colloid follicles.
Colloid fills the follicle cavities.
Follicle cells produce thyroglobulin.
I

5. THE THYROID glaND:

7. THYROID HORMONEs:
 There are two biologically active thyroid hormones:
- Tetraiodothyronine(T4; usually called thyroxine)
- Triiodothyronine (T3)
 Derived from modification of tyrosine(amino acid).

8. DIffERENcEs bETwEEN T4 aND T3:
• The thyroid secretes about 80mg of T4, but only 5mg of T3 per
day.
• However, T3 has a much greater biological activity about 10
folds than T4.
• An additional 25mg/day of T3 is produced by peripheral
monodeiodination of T4 by enzyme called 5’ Monodeiodenase.
thyroid
T4 T3
I-

9. MajOR sOuRcEs Of IODINE:
• Thyroid hormones are unique biological molecules in that they
incorporate iodine in their structure.
• Thus, adequate iodine intake either through diet or water is
required for normal thyroid hormone production.
• Major sources of iodine are:
- iodized salt
- iodated bread
- dairy products
- shellfish
• Minimum requirement(RDA): 75 micrograms/day
• US intake: 200 - 500 micrograms/day

10. IODINE METabOlIsM
• Dietary iodine is absorbed in the GI tract, then taken up by the
thyroid gland (or removed from the body by the kidneys).
• About 80% of the iodine is lost in urine where as only 20 % is
taken up by the Thyroid follicular cells.
• The transport of iodide into follicular cells is dependent upon a
Na+/I- co-transport system.
• Iodide taken up by the thyroid gland is oxidized by peroxide in
the lumen of the follicle:
Peroxidase
I -
I+
• Oxidized iodine can then be used in production of thyroid
hormones.

11. THE NExT sTEp: pRODucTION Of THYROglObulIN:
 Pituitary produces TSH, which binds to follicle cell receptors.
 The follicle cells of the thyroid produce thyroglobulin.
 Thyroglobulin is a very large glycoprotein.
 Thyroglobulin is released into the colloid space, where it’s
tyrosine residues are iodinated by I+.
 This results in formation of monoiodotyrosine or diiodotyrosine.

12. THYROID fOllIclEs wITH acTIvITIEs:

13. REGULATION:

14. ThyROId hORmONE SyNThESIS

15. TRANSpORT Of ThyROId hORmONES
• Thyroid hormones are lipid-soluble.
• Thus, they are found in the circulation associated with binding
proteins:
- Thyroid Hormone-Binding Globulin(TBG) (~70% of hormone)
- Pre-albumin(Transthyretin) (~15%)
- Albumin (~15%)
• Less than 1% of thyroid hormone is found free in the circulation.
• Only free and albumin-bound thyroid hormone is biologically
available to tissues.
• Among the amount of thyroid hormone production and release
T4 is approximately 95% and T3 is 5%. But biological active is
T3 so T4 is converted to T3 in peripheral tissues by the enzyme
5’monodeiodinase and become active.

16. CONvERSION Of T4 TO T3
 T3 has much greater biological activity than T4.
 A large amount of T4 (25%) is converted to T3 in peripheral
tissues.
 This conversion takes place mainly in the liver and kidneys. The
T3 formed is then released to the blood stream.
 In addition to T3, an equal amount of “Reverse T3” may also be
formed. This has no biological activity.
T3 MIT + DIT
Reverse T3 DIT + MIT

17. REGULATION Of ThyROId hORmONE LEvELS:
• Thyroid hormone synthesis and secretion is regulated by two
main mechanisms:
- An “auto regulation” mechanism, which reflects the
available levels of iodine.
- Regulation by the hypothalamus and anterior pituitary.

18. AUTO REGULATION Of ThyROId hORmONE
pROdUCTION
• The rate of iodine uptake and incorporation into thyroglobulin is
influenced by the amount of iodide available:
- Low iodide levels increase iodine transport into follicular cells
- High iodide levels decrease iodine transport into follicular cells
Thus, there is negative feedback regulation of iodide transport by
iodide.

19. NEUROENdOCRINE REGULATION Of ThyROId
hORmONES: ROLE Of TSh
• Thyroid-stimulating hormone (TSH) is produced by thyrotroph cells of
the anterior pituitary.
• TSH is a glycoprotein hormone composed of two subunits:
- alpha subunit (common to LH, FSH, TSH, hCG)
- TSH beta subunit, which gives specificity of receptor binding and
biological activity.

20. ACTION Of TSh ON ThE ThyROId
 TSH acts on follicular cells of the thyroid.
- increases iodide transport into follicular cells
- increases production and iodination of thyroglobulin
- increases endocytosis of colloid from lumen into follicular cells
Na+ K+ I- Na+
gene
ATP
follicle colloid droplet thyroglobulin I-
cell
endocytosis
thyroglobulin thyroglobulin
iodination I+ I-
T3 T4

21. mEChANISm Of ACTION Of TSh
• TSH binds to G protein-coupled receptor on thyroid follicular
cells.
• Specifically, it activates a Gs-coupled receptor which leads to
activation of Adenyl cyclase resulting in increased c-AMP
production and PKA (Protein Kinase-A) activation.
Adenylyl
TSH Cyclase
Gsa
ATP cyclic AMP
Follicle cell
Protein kinase
A

22. REGULATION Of TSh RELEASE fROm
ThE ANTERIOR pITUITARy
• TSH release is influenced by hypothalamic TRH, and by thyroid
hormones themselves.
• Thyroid hormones exert negative feedback on TSH release at
the level of the anterior pituitary.
- inhibition of TSH synthesis
- decrease in pituitary receptors for TRH
hypothalamus
+ TRH
TRH receptor
-
-
pituitary
TSH synthesis
T3/T4

23. INfLUENCE Of TRh ON TSh RELEASE
• Thyrotropin-releasing hormone (TRH) is a hypothalamic
releasing factor which travels through the pituitary portal system
to act on anterior pituitary Thyrotroph cells.
• TRH acts through G protein-coupled receptors, activating the IP3
(Ca2+) and DAG (PKC) pathways to cause increased production
and release of TSH.
IP3 calcium
G protein-coupled
receptor
TRH phospholipase C calmodulin
DAG PKC
• Thyroid hormones also inhibit TRH synthesis.

24. NEGATIvE fEEdbACk ACTIONS Of ThyROId
hORmONES ON TSh SyNThESIS ANd RELEASE
TRH synthesis
hypothalamus
+ TRH -
TRH receptor -
T3/T4
pituitary
-
TSH synthesis
TSH binds
Thyroid gland
follicle cell receptors

26. Other FactOrs regulating thyrOid hOrmOne
levels
• Diet: a high carbohydrate diet increases T3 levels, resulting
in increased metabolic rate (diet-induced thermogenesis).
• Low carbohydrate diets decrease T3 levels, resulting in
decreased metabolic rate.
• Cold Stress: increases T3 levels in other animals, but not in
humans.
• Any condition that increases body energy requirements (e.g.,
pregnancy, prolonged cold) stimulates hypothalamus 
TRH  TSH.

27. actiOns OF thyrOid hOrmOnes:
 Thyroid hormones are essential for normal growth of tissues,
including the nervous system.
 Lack of thyroid hormone during development results in short
stature and mental deficits (cretinism).
 Thyroid hormone stimulates or increase Basal Metabolic
Rate(BMR).

28. • Required for GH and prolactin production and secretion
• Required for GH action
• Increases intestinal glucose reabsorption (glucose
transporter)
• Increases mitochondrial oxidative phosphorylation (ATP
production)
• Increases activity of adrenal medulla (sympathetic; glucose
production)
• Induces enzyme synthesis
• Result: stimulation of growth of tissues and increased
metabolic rate. Increased heat production (calorigenic effect)

29. eFFects OF thyrOid hOrmOne On nutrient
sOurces:
• Effects on protein synthesis and degradation:
-increased protein synthesis at low thyroid hormone levels
(low metabolic rate; growth)
-increased protein degradation at high thyroid hormone levels
(high metabolic rate; energy)
• Effects on carbohydrates:
-low doses of thyroid hormone increase glycogen synthesis
(low metabolic rate; storage of energy)
- high doses increase glycogen breakdown (high metabolic
rate; glucose production)

30. One majOr target gene OF t3: the na+/K+
atPase PumP:
 Pumps sodium and potassium across cell membranes to
maintain resting membrane potential
 Activity of the Na+/K+ pump uses up energy, in the form of ATP
 About 1/3rd of all ATP in the body is used by the Na+/K+ ATPase
 T3 increases the synthesis of Na+/K+ pumps, markedly increasing
ATP consumption(BMR increases).
 T3 also acts on mitochondria to increase ATP synthesis(size and
number of mitochondria will increase).
 The resulting increased metabolic rate increases thermo genesis
(heat production).

31. Key POints:

32. thyrOid hOrmOne actiOns which increase
Oxygen cOnsumPtiOn
• Increase mitochondrial size, number and key enzymes.
• Increase plasma membrane Na-K ATPase activity.
• Increase futile(ineffective) thermogenic energy cycles.
• Decrease superoxide dismutase activity.

33. 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

34. eFFects OF thyrOid hOrmOnes On the
resPiratOry system
• Increase resting respiratory rate
• Increase minute ventilation
• Increase ventilatory response to hypercapnia and hypoxia

35. eFFects OF thyrOid hOrmOnes On the renal
system
• Increase blood flow
• Increase glomerular filtration rate(GFR)

36. eFFects OF thyrOid hOrmOnes On Oxygen-
carrying caPacity
• Increase RBC mass
• Increase oxygen dissociation from hemoglobin

37. EffEcts of 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

38. EffEcts 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.

39. EffEcts of 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

40. EffEcts of 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

42. thyroid hormonE dEficiEncy: hypothyroidism
 Early onset: Delayed/incomplete physical and mental
development.
 Later onset(Youth): Impaired physical growth
 Adult onset(Myxedema) : Gradual changes occur. Tiredness,
lethargy, decreased metabolic rate, slowing of mental function
and motor activity, cold intolerance, weight gain, goiter, hair loss,
dry skin. Eventually may result in coma.
 Causes:
(a) Insufficient iodine.
(b) Lack of thyroid gland.
(c) Lack of hormone receptors.
(d) Lack of TH binding globulin.

43. how is hypothyroidism rElatEd to GoitEr?
• During iodine deficiency, thyroid hormone production
decreases.
• This results in increased TSH release (less negative feedback).
• TSH acts on thyroid, increasing blood flow, and stimulating
follicular cells and increasing colloid production.

44. midwEst – thE GoitEr bElt
• If goiter is due to decreased I, then thyroid gland enlarges – called
endemic or colloidal goiter.
• Pituitary gland  TSH stimulate thyroid gland to produce TH, but
the only result is that the follicles accumulate more and more
unusable colloid.
• Cells eventually die from over activity and the gland atrophies.

45. thyroid hormonE ExcEss: hypErthyroidism
• Emotional symptoms (nervousness, irritability), fatigue, heat
intolerance, elevated metabolic rate, weight loss, tachycardia,
goiter, muscle wasting, apparent bulging of eyes(
exophthalmos), may develop congestive heart failure.
• Causes:
(a) Excessive TSH release.
(b) Autoimmune disorders.