thyroid hormone details

1. Production, Regulation, and Action
by Dr. Bhavika Vanani
MD Bio-chemistry
Unipath Speciality Laboratory

3. • The thyroid gland contains numerous follicles,
composed of epithelial follicle cells and colloid.
• Between follicles are clear parafollicular cells,
which produce Calcitonin.

4. Why is Iodine Important in Thyroid
Hormone Production?
• Thyroid hormones are unique biological
molecules in that they incorporate iodine in
their structure.
• Major sources of iodine:
- iodized salt
- iodated bread
- dairy products
- shellfish
• Minimum requirement: 75- 80
micrograms/day

5. 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).

6. 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 its tyrosine residues are
iodinated by I+
.
This results in tyrosine residues which have
one or two iodines attached
(monoiodotyrosine or diiodotyrosine).

7. Thyroid Hormones
 There are two biologically active thyroid
hormones:
- tetraiodothyronine (T4; usually called
thyroxine)
- triiodothyronine (T3)
 Derived from modification of tyrosine.

8. Differences between T4 and T3
The thyroid secretes about 80 micro gm of T4, but
only 5 micro gm of T3 per day.
However, T3 has a much greater biological activity
(about 10 X) than T4.
An additional 25 micro/day of T3 is produced by
peripheral monodeiodination of T4.
T4
thyroid
I-
T3

9. TRIIODOTHYRONINE( TETRAIODOTYROSINE
RAPID ACTION AND
DEGRADATION
SLOW TO RESPOND
10 x MORE RAPIDLY
BINDS TO RECEPTORS
SLOW BINDING
METABOLICALLY ACTIVE INACTIVE,CONVERTS TO
T3
DIFFERENCE IN ACTIONS OF T3 & T4

10. Transport of Thyroid Hormones
• Thyroid hormones are not very soluble in water
(but are lipid-soluble).
• Thus, they are found in the circulation associated
with binding proteins.
• Less than 1% of thyroid hormone is found free in
the circulation.
• Only free and albumin-bound thyroid hormone is
biologically available to tissues.

11. One Major Advantage of this System
The thyroid gland is capable of storing many
weeks worth of thyroid hormone (coupled to
Thyroglobulin).
If no iodine is available for this period,
thyroid hormone secretion will be
maintained.

12. 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.

13. Autoregulation of Thyroid Hormone
Production
The rate of iodine uptake and incorporation
into Thyroglobulin is influenced by the amount
of iodide available:
- Thus, there is negative feedback regulation of
iodide transport by iodide.

14. Neuroendocrine Regulation of Thyroid
Hormones: Role of TSH
 Thyroid-
stimulating
hormone (TSH) is
produced by
thyrotroph cells
of the anterior
pituitary.
α
LHβ
FSHβ TSHβ

LH FSH TSH

15. Action of TSH on the Thyroid
 TSH acts on the thyroid.
- increases iodide transport into follicular cells
- increases production and iodination of
Thyroglobulin
- increases endocytosis of colloid from lumen into
follicular cells

16. Mechanism of Action of TSH
TSH binds to a plasma membrane-bound, G
protein-coupled receptor on thyroid follicle cells.
Specifically, it activates a Gs-coupled receptor,
resulting in increased cAMP production and PKA
activation.
TSH
Gsa
Adenylyl
Cyclase
ATP cyclic AMP
Protein kinase
A
Follicle cell

17. Thyroid Follicles

18. hypothalamus
TRH
TRH receptor
TSH synthesis
pituitary
T3/T4
+
-
-
-
TRH synthesis
Thyroid gland
follicle cell receptors
TSH binds

19. Other Factors Regulating Thyroid Hormone
Levels
Diet: a high carbohydrate diet increase 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 (Pit)

20. 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 basal metabolic
rate.

21. Actions of Thyroid Hormone
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)

22. Expression and Regulation of Thyroid
Hormone Receptors
Thyroid hormone receptors are found in
many tissues of the body, but not in adult
brain, spleen, testes, uterus, and thyroid
gland itself.
Thyroid hormone inhibits thyroid hormone
receptor expression (TRE on THR genes).

23. Thyroid hormones:
Key Points
• Held in storage
• Bound to mitochondria, there by increasing ATP
production
• Bound to receptors activating genes that control energy
utilization
• Exert a calorigenic effect

24. 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.
 Many causes (insufficient iodine, lack of
thyroid gland, lack of hormone receptors, lack
of TH binding globulin….)

25. Hypothyroidism Symptoms
Tiredness and weakness
Dry skin
Feeling cold
Hair loss
Difficulty in concentrating and poor memory
Constipation
 Weight gain with poor
appetite
 Hoarse voice
 Menorrhagia, later
oligo and amenorrhoea
 Paresthesias
 Impaired hearing

26. Hypothyroidism Signs
Dry skin, cool extremities
Puffy face, hands and feet
Delayed tendon reflex
relaxation
Carpal tunnel syndrome
Bradycardia
Diffuse alopecia
Serous cavity effusions

27. Causes of Hypothyroidism
Autoimmune
hypothyroidism
(Hashimoto’s, atrophic
thyroiditis)
Iatrogenic (I123treatment,
thyroidectomy, external
irradiation of the neck)
Drugs: iodine excess,
lithium, antithyroid
drugs, etc
Iodine deficiency
Infiltrative disorders of
the thyroid: amyloidosis,
sarcoidosis,haemochroma
tosis, scleroderma

28. Causes of Hyperthyroidism
Most common causes
Graves disease
Toxic multinodular
goiter
Autonomously
functioning nodule
Rarer causes
Thyroiditis or other causes
of destruction
Thyrotoxicosis factitia
Iodine excess (Jod-Basedow
phenomenon)
Struma ovarii
Secondary causes (TSH or
ßHCG)

29. Hyperthyroidism Symptoms
Hyperactivity/ irritability/ dysphoria
Heat intolerance and sweating
Palpitations
Fatigue and weakness
Weight loss with increase of appetite
Diarrhoea
Polyuria
Oligomenorrhoea, loss of libido

30. Hyperthyroidism Signs
Tachycardia (AF)
Tremor
Goiter
Warm moist skin
Proximal muscle
weakness
Lid retraction or lag
Gynecomastia