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Thyroid

Thyroid
hormones
hormones
by
Juniadi Soetowo
Anatomy
and
histology
Posterior View of the Thyroid
gland 4
Thyroid Gland

Figure 23-7b: The thyroid gland


biosynthesis
AND
SECRETION
Thyroid Hormone Synthesis
Synthesis &
Secretion
of thyroid hormone
Thyroglobulin

Iodide trapping

Synthesis
of T3, T4 ● ● ● ●
● ●

● ●

TSH

TSH

Endocytosis



● ●
● ●


THYROID HORMONES SYNTHESIS

• Trapping of I- from the plasma by the thyroid gland.


• • Oxidation of I- to oxidative form by thyroid peroxidase.
• • Incorporation of I2 ( oxidative form ) into tyrosyl residues
on thyroglobulin in the colloid. Monoiodotyrosine (MIT) and
diiodotyrosine (DIT) are formed.
• • Production of T3 and T4 by coupling iodotyrosyl residues
in the thyroglobulin.
• • Splitting off of T4 and T3 from thyroglobulin.
• • Release of T4 and T3 into the circulation.

The plasma distribution of thyroid hormones is ~97% T4,


2% T3 and <1% rT3. Despite the greater plasma concentration
of T4, T3 is the actual active hormone of the thyroid gland.
Thyroid gland is capable of
hormone synthesis in the
11 wk of gestation.
th

TSH minimally crosses the


placenta, and T4 & T3
cross in limited amounts.
BLOOD IODINE LEVEL
Adequate dietary iodine is essential for normal
thyroid function(100-150 μg).
Low levels of iodine leads to decrease
synthesis and secretion of thyroid hormones and
this stimulates TSH hormone from the anterior
pituitary causing enlargement of thyroid gland
(goiter). Which may be simple or colloid goiter.
High levels of iodine depresses all the thyroid
functions and decreases the size of the gland and
it may block the response of the gland to TSH
(Wolff Chaikoff effect)
TrAnsport
and
metabolism
TRANSPORT T3 DAN T4
VIA TBG, TBA DAN TBPA
1-2mg % 25 mg %

1. % IKATAN T3 – TBG = % IKATAN T4 – TBG : 70 – 75 %

2. % IKATAN T3 – TBA LEBIH BESAR DPD IKATAN T4 – TBA


25-30% 5-10%

3. T4 TERIKAT PADA TBPA ( 15-20 % ), SEDANGKAN T3


TIDAK TERIKAT PADA TBPA.
5’

5
Thyroid hormone
metabolism

(Tetrac)
5’
5 T4

3’ 3
decarboxylation
( thyronamines )
Mechanism
of action
phenol degradation
Actions of Thyroid Hormones
De
Positive regulation of gene
expression by TH
Activated receptors bind to
hormone response elements
which are short specific sequences of
DNA which are located in promoters /
upstream of promoters of hormone –
responsive genes. In most cases,
hormone-receptor complexes bind
DNA in pairs.
Interaction of Thyroid Hormone
Receptors with DNA
Thyroid hormone receptors bind to short, repeated
sequences of DNA called thyroid or T3 response
elements (TREs), a type of hormone response
element.
A TRE is composed of two AGGTCA "half sites"
separated by four nucleotides. The half sites of a
TRE is arranged as direct repeats .
Thyroid
hormone
function
General actions of thyroid
hormones
1- Major effect of T3 & T4 is to enhance general protein synthesis essential
for growth.
for example: T3 enhances transcription of growth hormone (GH)
itself. (anabolic effects of T3)
However, very high T3 levels in blood causes inhibition of protein
synthesis.

2- Thyroid hormones are essential for normal physical, mental reproductive


development in humans.
Intrauterine or neonatal hypothyroidism causes cretinism in which
there is physical & mental retardation.

3- Thyroid hormones have metabolic actions that regulates


metabolism of carbohydrates, lipids & proteins.
Basal Metabolic rate (BMR) is increased.
METABOLIC EFFECTS AND ORGAN
FUNCTIONS

Physiological doses --------


stimulate protein synthesis.
Excess hormones ------ protein
catabolism
Carbohydrate metabolism
• Stimulate all aspects of CHO metabolism:
- Increase glucose uptake by cells.
- Stimulate glycolysis.
- Stimulate gluconeogenesis.
- Increase rate of glucose absorption from
GIT.
- Stimulate insulin secretion and Down-
regulate insulin receptors
- Hyperthyroid or hypothyroid : serum
glucose normal
Metabolisme Lemak
:.
Hipertiroid
• Lipolisis As. Lemak bebas (FFA)
• Lipogenesis
Lipolisis > Lipogenesis 
BB , Lemak , Kolesterol
Hipotiroid : lipolisis dan lipogenesis
BB , Kolesterol
Proses Metabolisme 
Kebutuhan vitamin
Hipertiroid :  defisiensi vitamin
merangsang sintesis vit-A dari
carotene di hati
Hipotiroid :  carotene plasma 
kulit kekuningan , defisiensi vitamin A
HIPERTIROID + TRIPTOFAN

DEFISIENSI PIRIDOKSIN

EKSKRESI ASAM XANTURENAT

HIPERTIROID + HISTIDIN

DEFISIENSI ASAM
FOLAT

EKSKRESI FORMIMINO GLUTAMAT


Intracellular effects of thyroid
hormones
1- Increase amino acids transport and protein
synthesis.
2- Increases glucose and fatty acids oxidation.
3- Increase size of mitochondria ------
----- ↑ O2 consumption & heat release.
4- Increase the activity of Na /K pump -------
------ ↑ transport of ions via cell membrane
with consumption of ATP
Calorigenic action:
• Regulates of Basal Metabolic Rate (BMR).

• Increases oxygen consumption in most


target tissues.

• Permissive actions: increases sensitivity of


target tissues to catecholamines, thereby
elevating lipolysis, glycogenolysis, and
gluconeogenesis.
Effects Of The 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
Effects Of The Thyroid Hormones
On
Oxygen Carrying Capacity

• Increase RBC mass by stimulating


bone marrow metabolism.
• Increase oxygen dissociation from
hemoglobin by increasing 2,3 DPG
Effects Of The 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
Efek pada Sist. Saraf Pusat
Penting untuk perkembangan mental

Hipotiroid sejak lahir  pubertas


gangguan mental dan pertumbuhan
karena gangguan pembentukan sel
saraf / korteks neuron / mielinisasi

Hipotiroid dewasa : daya ingat


gangguan psikis
Effects Of The Thyroid
Hormones On The Renal
System

• Increase renal blood flow


• Increase Glomerular filtration rate
Effects Of Thyroid Hormones
On The respiratory system

• Increase rate of metabolism and


utilization of O2 and formation of CO2 -
------ activate the mechanisms that
increase the rate and depth of
respiration.
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
Relation between thyroid and
catecholamines hormones
• The action of thyroid and catecholamines are
interrelated.
 Thyroid hormones increases the number and
affinity of β-adrenergic receptors in the heart
and possibly in other tissues.
 The effects of Thyroid H on the heart
resemble those of β-adrenergic stimulation.
 Although plasma catecholamine levels is
normal
Effects Of Thyroid Hormones On
The GIT
• Increase appetite and food
intake.
• Increase rate of secretion of the
digestive juices.
• Increase GIT motility.
MODULATOR PENTING PADA
PROSES PERTUMBUHAN
1. PROSES METAMORFOSIS AMFIBI

2. PEMBENTUKAN HbA

3. STIMULASI PEMBENTUKAN ENZIM


KARBAMOIL FOSFAT SINTETASE

4. PERTUMBUHAN MANUSIA ---- KRETINISME


Physical growth
• Essential for normal growth and skeletal
maturation by:
1- Stimulating the expression of the gene for
GH necessary for normal secretion of GH.
2- Potentiate the actions of somatomedins on
the tissues.
Effects Of The 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
Thyroid
regulation /
auto
regulation
Feedback control of thyroid
hormones
Control of thyroid
hormone synthesis
and release and
feedback control
TSH ( Thyroid Stimulating Hormone )
This hormone is secreted from the anterior pituitary gland
to increase thyroid hormone secretion. It increases CAMP
and has the following effects:
1- It increases the size and vascularity of the gland.
2- Increases iodide pump, glucose utilization and
O2 consumption in the gland
3- It increases all the steps required for formation
and release of thyroid hormones.
4- Prolonged stimulation of the gland with TSH
------- goiter.
Actions of TSH
• Active uptake of iodine*
• Stimulate other reactions involved
in thyroid hormone synthesis
• Stimulate the uptake of colloid
• Stimulate thyroid hormones
secretion
Thyroid Gland
Synthesis of T4 and T3 are stimulated by:
• ↑TSH

Synthesis of T4 and T3 are reduced by:


• ↓ TSH
• Glucocorticoid, dopamin and
somatostatine.
Autoregulation 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 iodine transport by iodide.
Wolff-Chaikoff
• Increasing doses of I- increase
hormone synthesis initially
• Higher doses cause cessation of
hormone formation ( organification: -)
• This effect is countered by the Iodide
leak from normal thyroid tissue.
• Patients with autoimmune thyroiditis
may fail to adapt and become
hypothyroid.
Wolff Chaikoff effect.
• Inhibition of the organic binding of iodine
in the gland.

• Inhibition of TSH effects on the gland by


reducing the response of CAMP to its
actions.

• Inhibition of the proteolysis of thyro -


globulin and release of thyroid hormones.
Jod-Basedow (yod-grave )
• Aberration of the Wolff-Chaikoff effect

• Excessive iodine loads induce hyperthyroi -


dism

• Observed in several disease processes


– Graves’ disease ( Diffuse toxic goiter )
– Multinodular goiter ( Plummer disease )