Thyroid hormone synthesis, their function, Thyroid disorders , Thyroid function tests

1. Thyroid Hormones ,
Thyroid Disorders &
Thyroid Function
Tests
Dr. Ifat Ara Begum
Associate Professor
Department of Biochemistry
Sir Salimullah Medical
College, Dhaka
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2. The thyroid is an endocrine
gland in vertebrates
 It is located anterior to the trachea,
just inferior to the larynx
 It consists of two connected lobes
 The lower two thirds of the lobes
are connected by a thin band
of tissue called the thyroid isthmus
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3. Each of the thyroid lobes are
embedded with parathyroid glands,
primarily on their posterior surfaces.
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The tissue of the thyroid
gland is composed mostly
of thyroid follicles
The follicles are
surrounded by a wall of
epithelial follicle cells & are
made up of a central cavity
filled with a sticky fluid
called colloid
The colloid is the center of
thyroid hormone
production and this
production is dependent on
iodine

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Types of thyroid hormone

6. Two types of thyroid hormones :
 Thyroxine / Tetraiodothyronine /
T4
 Triiodothyronine / T3
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Synthesis of thyroid
hormone

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Blood Follicular cell
Lumen

9. 1. Synthesis of thyroglobulin (Tg) : A
glycoprotein synthesized from tyrosine
residues in follicular cells, then secreted into
follicular lumen
2. Iodide (I-) trapping: Uptake of iodide from blood
by follicular cells actively against conc.
gradient. It is stimulated by TSH
3. Conversion of iodide to elemental iodine (I2)
by oxidation of iodide in luminal surface (apical
membrane) of follicular cells, catalyzed by
TPO (thyroperoxidase)
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10. 4. Organification of Tg & synthesis of
iodotyrosine (MIT, DIT):
It is done by iodination of tyrosine
residues of Tg in apical membrane of
follicular cells, catalyzed by TPO and
stimulated by TSH
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11. 5. Coupling of MIT & DIT within Tg molecule to form
T3, T4, rT3 catalyzed by TPO and stimulated by TSH
MIT + DIT = T3
DIT + DIT = T4
Some T4 converts to rT3
6. Storage of Tg with iodinated compounds within
follicular lumen as colloid material.
So, colloid is Tg molecule made of uncoupled DIT,
uncoupled MIT, T3, T4 & rT3
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12. 7. Uptake of colloid by follicular cells & release
of iodinated compounds :
Colloids are taken up by follicular cells &
lysosomal proteolytic enzymes of cells split off
the iodothyronines (T3, T4) & uncoupled
iodotyrosines (MIT, DIT) by proteolysis. It is
stimulated by TSH
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13. 8. Deiodination of uncoupled DIT, MIT by
deiodinase with release of iodide that is recycled
and reused within follicular cells
9. Secretion of iodothyronines (T3, T4) from
follicular cells to blood
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Release & Transport of Thyroid
Hormone

15. Thyroid
gland
95% thyroxine (T4
)
5% triiodothyronine
(T3)
On coming to
blood , 40% T4
is converted to
T3
On coming to
blood , 40%
T4 is
converted to
rT3
Rest 20%
remain as T4
in blood
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16. > 99.5% of T3 and T4 circulates in blood
bound with transport proteins:
- 80% thyroid binding globulin
- 10% Trans thyrectin / pre-albumin
- 10% albumin
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17. It is the free thyroid hormone which
 is physiologically active
 determines thyroid status of a person
 is under control of hypothalamo – pituitary -
thyroid feedback response
 inhibits TSH secretion by negative feed back
effect
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Regulation of Thyroid Hormone
secretion

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Mechanism of action of thyroid
hormones

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Differences between T3 and T4

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Points T3 T4
Iodination of
tyrosine
By 03 iodine atom By 04 iodine atom
Production in
thyroid gland
directly
20% 100%
Production in
peripheral
conversion
Yes, from T4 (80% of
T3)
No

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Points T3 T4
Conversion to
rT3
No Yes
Free
/unbound form
0.3% 0.02%
Half life 1 day 1 week
Potency 4 times more than T4 Less potent than T3

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Functions of Thyroid
Hormone

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Calorigenic function /
thermogenesis & Increases
oxygen consumption
Facilitates:
- good mentation
- good cerebration
- good reflex activity
- normal sexual function
Helps in:
- normal growth
- skeletal maturation
- CNS development
- Growth & development of
brain during fetal life & in
1st few years of postnatal
life

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Effect on intermediary
metabolism:
Carbohydrate metabolism:
- Increase glucose
absorption from intestine
- Increase cellular uptake of
glucose
- Stimulates glycolysis,
glycogenolysis &
gluconeogenesis
Protein metabolism:
- Increases protein synthesis
- Causes positive nitrogen
balance
Lipid metabolism:
- Stimulates lipolysis
- Increases plasma FFA
concentration
- Facilitates cholesterol
excretion & FA oxidation

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Effect on cardiovascular
system:
Increases
- Heart rate
- Force of contraction
- Cardiac output
- Tissue perfusion
Maintains:
- Good appetite
- Good GIT activity

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Common Thyroid Disorders

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 Hypothyroidism
 Hyperthyroidism
 Goiter with / without abnormal
thyroid hormone secretion

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Hypothyroidis
m vs.
Hyperthyroidis
m

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Points Hypothyroidism Hyperthyroidism
Definition Clinical condition
produced by insufficient
circulating thyroid
hormones due to their
decreased synthesis
Clinical condition
produced by excess
circulating thyroid
hormones due to their
increased synthesis
Metabolic
effects
Decreased BMR, cold
intolerance, tiredness
Increased BMR, heat
intolerance, sweating
Weight gain despite
relative lack of appetite
Weight loss in spite of
increased appetite

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Points Hypothyroidism Hyperthyroidis
m
Skin Dry, thick & puffy skin due to
accumulation of MPS
Warm & moist
skin
Face Puffy face -
Voice Slow & husky -
Memory &
mentation
Poor memory & slow mentation
in thought, speech & action
-
Edema Free water retention leading to
swelling of body and peripheral
edema
-

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Points Hypothyroidism Hyperthyroidism
Ocular
effects
Bagginess under eye Exophthalmos,
ophthalmoplegia
Cardiovascu
lar effects
- Tachycardia, palpitation,
fibrillation
Neurological
effects
Myopathy, carpal
tunnel syndrome
Tremor, psychosis,
irritability, excess sweating
Myopathy - Thyrotoxic myopathy
(proximal myopathy with
weakness & atrophy

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Points Hypothyroidism Hyperthyroidism
Reproductiv
e effects
Menstrual irregularities Menstrual irregularities
Loss of libido,
impotency , infertility
Loss of libido, impotency ,
infertility

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Myxedema
vs.
Cretinism

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A) Myxedema:
 Syndrome of
hypothyroidism in adult
 Presents with low T3 , low
T4 , high TSH
Myxedematous
appearance: MPS deposits
in skin which binds with water
to produce indurated edema
& Myxedematous appearance
Myxedema
madness: severe
mental symptoms like
slow mentation, poor
memory, paranoid
delusion
Myxedema heart:
Cardiac features like
cardiomegaly, rise of
cardiac markers, ECG
change etc
Myxedema coma: severe life threatening manifestation of
hypothyroidism

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B) Cretinism / Hypothyroid
dwarf
 Syndrome of hypothyroidism in
children since birth / fetal life
 Presents with low T3 , low T4 ,
high TSH
Growth failure :
Children are dwarfed
& mentally retarded
 Skeletal growth is more reduced than soft tissue growth with
relative enlargement of soft tissues.
So, typically they present with potbelly, enlarged protruding
tongue & stocky appearance

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Points Cretinism Myxedema
What is this? Hypothyroidism in
infants & children
Hypothyroidism in
adult
Growth failure Present Absent
Short stature Present Absent
Mental retardation Present Absent
Indurated
cutaneous edema
Absent Present
Potbelly & stocky
appearance
Present Absent

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Dwarfism
vs.
Cretinism

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Points Cretinism Dwarfism
Cause Thyroid hormone
deficiency
Growth hormone
deficiency
Mental
retardation
Present Absent
Pattern of
growth
failure
Skeletal growth is more
reduced than soft tissue
growth
All parts grow in
appropriate proportion
but at a very low rate
Feature of
soft tissue
overgrowth
Present Absent

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Thyroid Function Tests

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Principle of thyroid function tests:
1. Measurement of thyroid hormones in blood
2. Assessment of hypothalamo-pituitary-thyroid axis by
stimulation test or suppression test
3. Evaluation of iodine metabolism by RAIUT (Radio active
iodine uptake test)
4. Evaluation of thyroid size
5. Measurement of thyroid autoantibodies
6. Evaluation of the effects of thyroid hormone on peripheral
tissues

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1. Measurement of plasma TSH
concentration:
TSH Thyroid Status
High Primary hypothyroidism (Thyroid
cause)
Low Secondary hypothyroidism (Pituitary /
Hypothalamic cause)
Very low /
Undetectable
Hyperthyroidism

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2. Measurement of plasma thyroid hormone
concentration:
Thyroid hormone
(T3 , T4 )
Thyroid Status
Decreased Hypothyroidism
Increased Hyperthyroidism

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3. Radio Active Iodine Uptake Test
RRAIU Test status Thyroid Status
Low uptake Hypothyroidism
High uptake Hyperthyroidism

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4. Measurement of thyroid autoantibody
Example of
autoantibodies
Found Positive in
Anti-TPO antibody, anti-
thyroglobulin antibody,
TSH receptor blocking
antibody etc
Autoimmune thyroiditis
Graves disease

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5. Other tests:
- TRH test
- TSH stimulation test
- T3 suppression test

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Hormonal scenario of
Thyroid disorders

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Free T3 Free T4 TSH Diagnosis
Normal Normal Normal Euthyroid
Normal Normal High Subclinical
hypothyroid
Low Low High Primary hypothyroid
Low Low Low Secondary
hypothyroid
Normal Normal Low Subclinical
hyperthyroid
High High Low Primary hyperthyroid
High High High Secondary
hyperthyroid
High Normal Low T3 hyperthyroid

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