K4A - Fisiologi Tiroid

8/10/2019 K4A - Fisiologi Tiroid

1/99

FISIOLOGI HORMON

METABOLIK TIROID

dr. Tri Jauhari P, SpPD, MBiomed, MSc

Bagian Fisiologi/Ilmu Penyakit Dalam

FK UNSOED/RSMS


2/99

PENDAHULUAN

Sistem endokrin: sistem kontrol tubuh,kelenjar, darah,organ target,tanpasaluran

Respon lambat : menit, jam,bulan, atautahun.

Komunikasi: melalui media yaitu

HORMON ("pembawa pesan melaluialiran darah ke berbagai sel)


3/99

PENDAHULUAN

Sifat hormon: Bekerja spesifikpada organ, bagian tubuh

tertentu atau aktivitas tertentu

Dihasilkan tubuh dalam jumlah yang sangat

sedikit tetapi memiliki pengaruh besarterhadap aktivitas tertentu dalam tubuh

Bekerja lambat,pengaruh hormon tidakspontan seperti pada pengaturan oleh

syaraf

Sebagai senyawa kimia, hormon tidakdihasilkan setiap waktu. Hormon diproduksihanya apabila dibutuhkan


4/99


5/99

Introduction.

Thyroid gland maintains levels of metabolism intissues.

Thyroid hormones stimulate oxygen consumption inmost cells of the body.

Regulates lipid and CHO metabolism. Necessary for normal growth and maturation.

Absence causes mental and physical slowing.

Excess causes body wasting nervousness tachycardiaand tremors.

Controlled by Thyroid stimulating hormones(TSH)


6/99

Formation and secretion of thyroid hormones.

The principal hormones secreted by thyroid gland are

Thyroxine(T4) and triiodothyronine(T3)

T3 is also formed in the peripheral tissue by

deiodination of T4 Both hormones are iodine-containing amino acids.

T3 is more active than T4

Calcitonin is also produced by thyroid in response toincreased calcium levels.


7/99

Structure of thyroid hormones


8/99

Thyroglobulin.

T3 and T4 are synthesized in the colloid by iodination

The hormones are bound to thyroglobulin within thethyroid cells

Thyroglobulin is also synthesized in the thyroid cells

The hormones remain bound to thyroglobulin untilsecreted

When secreted, the colloids is ingested by thyroidcells, peptide bonds are hydrolyzed and free T3 and

T4 are discharged into the system


9/99

Iodine Metabolism

Iodine is the raw material for thyroid hormone

synthesis.

Ingested iodine is converted to iodide and

then absorbed

The principal organs that take up the iodide

are the thyroid which uses it to make thyroid

hormones and the kidneys which excrete it in

the urine.


10/99

Iodide trapping

Thyroid concentrates iodide by activelytransporting it from circulation to the colloid

The transport mechanism is called iodide

trapping mechanism or the iodide pump The pump is an example of a secondary active

transport system

In the gland, iodide is oxidized and bound totyrosine.


11/99

Thyroid Hormone synthesis

In the thyroid, iodide is oxidized to iodine and boundwithin secs to tyrosine attached to thyroglobulin

The enzyme responsible for the oxidation andbinding of iodide is Thyroid peroxidase

Monoiodotyrosine (MIT) is next iodinated toDiiodotyrosine(DIT)

2 DIT molecules undergo oxidative condensation toform Thyroxine(T4)

T3 is probably formed by condensation of MIT andDIT.


12/99

Synthesis and Secretion of the Thyroid Metabolic Hormones

Iodine is Required for the Formation of Thyroxine

a. Iodine in the form of iodides; 1.0 mg/wk

b. Of the iodide absorbed from the intestine, 80% israpidly excreted by the kidneys, and 20% is

selectively removed by cells of the thyroid gland


13/99


Iodide Pump-the Sodium-Iodide Symporter

(Iodide Trapping)

Fir. 76.2 Thyroid cellular mechanisms for iodine transport, thyroxine and

triiodothyronine formation, and thyroxine and triiodithyronine

release into the blood


14/99


15/99


Iodide Pump-the Sodium-Iodide Symporter

(Iodide Trapping)

a. Transport of iodine from the bloodb. Formation and secretion of thyroglobulin by the

thyroid cells

c. Oxidation of the iodide ion

d. Iodination of tyrosine and formation of the thyroidhormone (organification of thyroid)


16/99


17/99


e. Storage of thyroglobulin-enough is stored to last the

body for 2-3 months

f. Release of throxine and triiodithyronine-cleaved from

the thyroglobulin and then released into the blood

g. Daily rate of secretion; 93% is normally thyroxine and

7% triiodothyronine. However, about of thethyroxine is slowly deiodinated to form the T3 so the

tissues get mainly T3


18/99


19/99


h. Thyroxine and triodothyronine are transported bound

to plasma proteins

i. Because of the high affinity to the plasma proteins,

the hormone is released very slowly

j. Thyroid hormones have slow onset and long duration

of action


20/99


Fig. 76.4 Approximate prolonged effect on the basal metabolic rate caused by

administering a single large dose of thyroxine


21/99

Transport and metabolism of Thyroid

Hormones

Large amounts of T3 and T4 are bound to plasma proteins.

The unbound T3 and T4 are the physiologically active forms of the

hormones.

Free T3 and T4 inhibit the secretion of TSH.

The plasma proteins that bind thyroid hormones are

albumin,transthyretin and thyroxin-binding globulin(TBG)

Most of the circulating T4 is bound to TBG

T3 is bound to albumin

TBG levels are increased in estrogen-treated patients and

pregnant women

TBG levels are reduced by glucocorticoids and androgens.


22/99

Physiological Functions of the Thyroid Hormones

Thyroid Hormones Increase the Transcription of

Large Numbers of Genes

a. Most of the thyroxine secreted by the thyroid is

converted to triiodothyronine (T3)

b. Thyroid hormones activate nuclear receptors


23/99


Fig. 76.5 Thyroid hormone

activation of target cells


24/99


Thyroid Hormones Increase Metabolic Activity-

(increase the BMR 60-100x)

a. Thyroid hormones increase the number and activityof mitochondria

b. Increase the active transport of ions through the

cell membrane (sodium and potassium)


25/99


Thyroid Hormones Effect on Growth

a. Promote the growth and development of the brain

during fetal life and first years of postnatal life

b. Deficiency will retard growth during growing

years


26/99


Effect on Specific Bodily Mechanisms

a. Stimulation of cbh metabolism-rapid uptake of

glucose, enhanced glycolysis, enhanced gluconeo-genesis, increased rate of absorption, increased

insulin secretion

b. Stimulation of fat metabolism-lipids are mobilizedrapidly decreasing fat stores, increases free fatty

acid concentration in plasma, and accelerates the

oxidation of free fatty acids in cells


27/99


Effect on Specific Bodily Mechanisms

c. Increased thyroid hormone decreases the

concentrations of cholesterol, phospholipids, andtriglycerides in plasma and vice versa; increases

the cholesterol secretion in bile

Increased Requirement for Vitamins

Increased Metabolic Rate

Decreased Body Weight


28/99


Fig. 76.6 Approximate relation of daily rate of thyroid hormone

(T4 and T3) to the basal metabolic rate


29/99


Effect on the Cardiovascular System

a. Increased blood flow and cardiac output

b. Increased heart ratec. Increased heart strength

d. Normal arterial pressure

Increased Respiration Increased Gastrointestinal Motility

Excitatory Effects on the CNS

Muscles React With Vigor


30/99


Muscle Tremors with Hyperthyroidism

Difficulty in Sleeping and Constant Tiredness

With Hyperthyroidism

Increased Thyroid Hormone Increases theSecretion of Several Other Endocrine Glands

Needs to be Normal for Normal Sexual Function


31/99

Regulation of Thyroid Hormone Secretion

TSH (Anterior Pituitary) Increases Thyroid Secretion

a. Increased proteolysis of the thyroglobulin

b. Increased activity of the iodide pumpc. Increased iodination tyrosine

d. Increased size and secretory activity of the thyroid

cells

e. Increased number of thyroid cells

Cyclic AMP Mediates the Stimulatory Effect of TSH-

acting as a second messenger system


32/99


Secretion of TSH is Regulated by Thyrotropin-

Releasing Hormone from the Hypothalamus

Feedback Effect of Thyroid Hormone to Decrease

the Secretion of TSH

Fig. 76.7 Regulation of thyroid secretion


33/99

w

TRH


34/99


35/99


36/99


Diseases of the Thyroid

a. Hyperthyroidism-Graves Disease, toxic goiter

b. Symptoms of hyperthyroidism

1) High state of excitability

2) Intolerance to heat

3) Mild to extreme weight loss

4) Varying degrees of diarrhea

5) Muscle weakness

6) Extreme fatigue

7) Tremor of the hands

8) Exophthalmos


37/99


Diseases of the Thyroid

c. Hypothyroidism-endemic colloidal goiter caused by

iodine deficiency

a. Symptoms of hypothyroidism

1) Myxedema

2) Cretinism


38/99

Iodine deficiency

When dietary intake drops,thyroid hormones

synthesis is inadequate and secretion is

reduced.

TSH is increased and thyroid hypertrophies

producing an iodine deficiency Goiter.

Endemic goiter-mountainous areas..


39/99

Iodine deficiency.


40/99

Cretinism

Children with hypothyroidism from birth are calledcretins

They have reduced growth and mentally retarded.

Potbellies

Enlarged protruding tongue

Causes-

Maternal iodine deficiency

Fetal thyroid dysgenesis

Inborn errors of thyroid synthesis

Maternal antibodies that cross placenta

Fetal hypo pituitary hypothyroidism


41/99


42/99

Clinical correlates.

Signs and symptoms of hypo or hyper thyroidism areconsequences of effect of thyroid hormones.

Hypothyroidism-

Syndrome of hypothyroidism is called myxedema.

Term also used to describe skin changes inhypothyroidism.

May be end result of secondary pituitary failure (pituitaryhypothyroidism)

May be due to hypothalamic failure( hypothalamichypothyroidism)

May be due to thyroid disorder.


43/99

EXAMPLES OF THYROID DISEASES

Hypothyroidism Hyperthyroidism


44/99

goiter

cretinism


45/99


46/99

There are two biologically active thyroid hormones:

- tetraiodothyronine (T4; usually called thyroxine)

- triiodothyronine (T3)

Derived from modification of an amino acid (tyrosine)

Thyroid Hormones

Diff b t T4 d T3


47/99

The thyroid secretes about 80 micrograms of T4, but only

5 micrograms of T3per day.

However, T3 has a much greater biological activity (about

10X) than T4.

An additional 25 micrograms/day of T3 is produced by

peripheral monodeiodinationof T4.

T4

thyroid

I-

T3

Differences between T4 and T3


48/99

Thyroid hormones are unique biologicalmolecules inthat they incorporate iodine in their structure.

Thus, adequate iodine intake (diet, water) is requiredfor normal thyroid hormone production.

Major sources of iodine:

- iodized salt- iodated bread

- dairy products

Minimum requirement: 75 micrograms/day

US intake: 200 - 500 micrograms/day

Why is Iodine Important in Thyroid Hormone Production?

I di M t b li


49/99

Dietary iodine is absorbedin the GI tract, then taken up

by the thyroid gland (or removed from the body by thekidneys).

The transportof iodide into follicular cells is dependent

upon a sodium/iodine cotransport system.

Iodide taken up by the thyroid gland is oxidizedby

peroxide in the lumen of the follicle:

peroxidaseI- I+

Oxidized iodine can then be used in production of

thyroid hormones.

Iodine Metabolism


50/99

The Next Step: Production of T3 or T4


51/99

The follicle cells of the thyroid produce thyroglobulin.

Thyroglobulinis a very large glycoprotein.

Thyroglobulinis released into the colloid space,

where its tyrosine residues are iodinated by I+

. This results in monoiodotyrosine (MIT) or

diiodotyrosine (DIT).

The first Step: Production of thyroglobulin

Initial Steps in Thyroid Hormone Synthesis


52/99

follicle

cell

extracellular space

colloid space

I-

I-

thyroglobulinwith

monoiodotyrosines and

diiodotyrosines

iodination

thyroglobulin

thyroglobulin

gene

I+oxidation

I-Na+ Na+K+

Initial Steps inThyroid Hormone Synthesis


53/99

The iodinated tyrosine residues on thyroglobulin are

modified and joined to form T3 and T4, still attached

to the thyroglobulin molecule.

Second step: Production of Thyroid Hormones

from Iodinated Thyroglobulin


54/99

In order to secrete T3/T4, the thyroglobulin in the

colloid space is internalized by endocytosisbackinto the follicle cell.

This internalized vesicle joins with a lysosome,whose enzymes cause cleavage of T3 and T4 fromthyroglobulin. Some T4 is converted to T3 at this

point.

T3 and T4 are then released into the extracellularspace by diffusion.

Only minute amounts of thyroglobulin arereleased into the circulation.

Utilization of Thyroglobulin to Secrete Thyroid Hormones


55/99

Utilization of Thyroglobulin to Secrete Thyroid Hormones

folliclecell

colloid space

endocytosis

thyroglobulin

T3 T4

colloid droplet

lysosome

T3/T4

(deiodinated, recycled)

extracellular space

(T4 T3)

Transport of Thyroid Hormones


56/99

Thyroid hormones are not very soluble in water(but are lipid soluble).

Thus, they are found in the circulation associatedwith binding proteins:

- Thyroid Hormone-Binding Globulin(~70% ofhormone)

- Pre-albumin (transthyretin), (~15%)- Albumin(~15%)

Less than 1% of thyroid hormone is found free inthe circulation.

Only free and albumin-bound thyroid hormone isbiologically available to tissues.

Transport of Thyroid Hormones


57/99

Transthyretin (TTR) is a serum and

CSF carrier of the thyroxine (T4) and

retinol. This is how transthyretin

gained its name, transports thyroxineand retinol.

TTR was originally called

prealbumin because it ran faster than

albumins on electrophoresis gels.

In CSF it is the primary carrier of T4,

as albumin is not present. TTR also

acts as a carrier of retinol (vitamin A)

through an association with retinol-

binding protein (RBP).

Transthyretin (prealbumin, amyloidosis type I)


58/99

T3 has much greater biological activity than T4.

A large amount of T4 (25%) is converted to T3 inperipheral tissues.

This conversion takes place mainly in the liverand

kidneys. The T3 formed is then released to theblood stream.

In addition to T3, an equal amount of reverse T3may also be formed. This has no biological

activity.

Conversion of T4 to T3


59/99

T4

R

3,3-T2

R

T3

Step up

R

rT3

Step down

THYROID HORMONE METABOLISM


60/99

Three deiodinases (D1, D2 & D3)catalyze thegeneration and/disposal of bioactive thyroid hormone.

D1 & D2 bioactivate thyroid hormone by removing

a single outer-ring iodine atom.

D3 inactivates thyroid hormone by removing a

single inner-ringiodine atom.

All family members contain the novel amino acid

selenocysteine (Se-Cys) in their catalytic center.

THYROID HORMONE DEIODINASES


61/99

NH2extracellular domain

intracellular domainCOOH

BASIC ORGANIZATION OF THE

SELENODEIODINASES

EXISTS AS ADIMER

Se-Cys

Thyroxine and its precursors: Structure & Synthesis


62/99

Thyroid hormones are made from tyrosine and iodine




63/99

Thyroid hormone synthesis



64/99

The thyroid gland is capable of storing manyweeks worth of thyroid hormone(coupled tothyroglobulin).

If no iodine is available for this period, thyroidhormone secretion will be maintained.

One Major Advantage of this System


65/99

Thyroid hormone synthesis and secretion isregulated by two main mechanisms:

- an autoregulation mechanism, whichreflects the available levels of iodine

- regulation by the hypothalamus and anteriorpituitary

Regulation of Thyroid Hormone Levels

A t l ti f Th id H P d ti


66/99

The rate of iodine uptake and incorporation into

thyroglobulin is influenced by the amount ofiodide available:

- low iodide levels increase iodine transportinto

follicular cells

- high iodide levels decrease iodine transportinto

follicular cells

Thus, there is negative feedback regulationof iodide

transport by iodide.

Autoregulation of Thyroid Hormone Production

Neuroendocrine Regulation of Thyroid Hormones:


67/99

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)

- TSH beta subunit, which gives specificity of receptor binding andbiological activity

a

LHbFSHb TSHb

LH FSH TSH

Role of TSH

Feedback regulation


68/99

Feedback regulation

the hypothalamic-pituitary-thyroid axis

Hormones derived from the pituitary thatregulate the synthesis and/or secretion of other

hormones are known astrophichormones.

Key players for the thyroid include:

TRH - ThyrotropinReleasing Hormone

TSH - Thyroid Stimulating Hormone

T4/T3- Thyroid hormones


69/99

T3 & T4 Control Pathways

& Diseases from Malfunction

Action of TSH on the Thyroid


70/99

TSH acts on follicular cells of the thyroid.

- increases iodide transportinto follicular cells

- increases production and iodination of thyroglobulin- increases endocytosis of colloidfrom lumen into follicular cells

Na+

I-thyroglobulinfolliclecell

gene

I-

endocytosis

thyroglobulin

T3 T4

colloid droplet

I-I+iodinationthyroglobulin

Na+ K+

ATP

y

1

2

3

Mechanism of Action of TSH


71/99

TSH binds to a plasma membrane-bound, G protein-coupled receptor on thyroid follicle cells.

Specifically, it activates a Gs-coupled receptor, resulting inincreased cyclic AMPproduction and PKAactivation.

TSH

Gsa

Adenylyl

Cyclase

ATP cyclic AMP

Protein kinase

A

Follicle cell

ec a s o ct o o S

Regulation of TSH Release from the Anterior Pituitary


72/99

TSH release is influenced by hypothalamic TRH, and bythyroid hormones themselves.

Thyroid hormones exert negative feedback on TSH releaseat the level of the anterior pituitary.

- inhibition of TSH synthesis

- decrease inpituitary receptors for TRH

hypothalamus

TRH

TRH receptor

TSH synthesispituitary T3/T4

+

--

g y

Regulation of TSH Release from the Anterior Pituitary


73/99

Thyrotropin-releasing hormone (TRH) is a hypothalamicreleasing 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 (calcium) and DAG (PKC) pathways to causeincreased production and release of TSH.

TRH phospholipase C

G protein-coupled

receptor

IP3 calcium

DAG PKC

calmodulin

Thyroid hormones also inhibit TRH synthesis.

Negative Feedback Actions of Thyroid Hormones on


74/99

hypothalamus

TRH

TRH receptor

TSH synthesispituitary

T3/T4

+

--

-

TRH synthesis

TSH Synthesis & Release

PITUITARY-THYROTROPE CELL


75/99

TSH regulation of


76/99

TSH binds to specific cell surface receptors thatstimulate adenylate cyclase to produce cAMP.

TSH increases metabolic activity that is required to

synthesize Thyroglobulin (Tg)and generate peroxide. TSH stimulates both I-uptakeand iodination of

tyrosine resides on Tg.

TSH regulation of

thyroid function

I t t b th th id f lli l ll


77/99

Ion transport by the thyroid follicular cell

I- I-organification

Propylthiouracil (PTU) blocksiodination of thyroglobulin

COLLOID

BLOOD

NaI symporter (NIS)

Thyroid peroxidase (TPO)

PTU, a thioamide drug used to treat hyperthyroidism

THYROGLOBULIN SYNTHESIS IN THE


78/99

IodinationofTyr residues of Tg

COLLOID

TSH

TSH receptorTPO

THYROGLOBULIN SYNTHESIS IN THE

THYROID FOLLICULAR CELL

THYROID HORMONE SECRETION BY THE


79/99

THYROID HORMONE SECRETION BY THE

THYROID FOLLICULAR CELL

COLLOID

TSHTSH receptor

DIT

MIT I-

T4T3

Other Factors Regulating Thyroid Hormone Levels


80/99

Diet: a high carbohydrate diet increasesT3 levels,resulting in increased metabolic rate (diet-induced

thermogenesis).

Low carbohydrate diets decreaseT3 levels, resulting in

decreased metabolic rate.

Cold Stress: increases T3 levels in other animals, but

not in humans.

Other Factors Regulating Thyroid Hormone Levels

Actions of Thyroid Hormones


81/99

Required for GH and prolactin production & 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.

Actions of Thyroid Hormones


82/99

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.

What are the specific actions of thyroid hormoneon body systems?

y

Cardiovascular system:Thyroid hormones increases heart


83/99

y y

rate, cardiac contractility and cardiac output. They also

promote vasodilation, which leads to enhanced blood flow to

many organs.Central nervous system:Both decreased and increased

concentrations of thyroid hormones lead to alterations in

mental

state. Too little thyroid hormone, and the individual tends to

feel

mentally sluggish, while too much induces anxiety and

nervousness.

Reproductive system:Normal reproductive behavior and

physiology is dependent on having essentially normal levels ofthyroid hormone. Hypothyroidism in particular is commonly

associated with infertility.

f f h d h d l


84/99

TH is critical for normal development of the skeletalsystem and musculature.

TH is also essential for normal brain development andregulates synaptogenesis, neuronal integration,

myelination and cell migration. Cretinismis a condition of severely stunted physical

and mental growth due to untreated congenitaldeficiency of thyroid hormones (congenital

hypothyroidism) due to maternal nutritional deficiencyof iodine.

Specific actions of thyroid hormone: development

Eff t t i th i d d d ti

Effects of Thyroid Hormone on Nutrient Sources


85/99

Effects on protein synthesis and degradation:

-increased protein synthesisat low thyroid hormone levels(low metabolic rate; growth)

-increased protein degradation at high thyroid hormone levels(high metabolic rate; energy)

Effects on carbohydrates:

-low dosesof thyroid hormone increase glycogen synthesis(low metabolic rate; storage of energy)

- high dosesincrease glycogen breakdown(high metabolic rate;glucose production)

Effects on Lipids:Increased thyroid hormone levels stimulate fatmobilization, leading to increased concentrations of fatty acidsin plasma. They also enhance oxidation of fatty acids in many

tissues. Finally, plasma concentrations of cholesterol andtriglycerides are inversely correlated with TH levels.

Mechanism of Action of T3


86/99

T3/T4 acts through the thyroid hormone receptor- intracellular, in steroid receptor superfamily

- acts as a transcription factor

- receptor binds to TRE on 5 flanking region of genes as

homodimers and/or heterodimers.- multiple forms (alphas and betas) exist

- one form (alpha-2) is an antagonist at the TRE

More on Receptor Coactivators and Corepressors


87/99

When not bound to hormone, the thyroid hormone

receptor binds to target DNA (TRE on 5 flanking region). Itis associated with corepressor proteinsthat cause DNA to

be tightly wound and inhibit transcription.

Binding of hormone causes a conformational change,

resulting in loss of corepressor binding and association with

coactivator proteins, which loosen DNA structure and

stimulate transcription.

Expression and Regulation


88/99

Thyroid hormone receptors are found in many tissues of

the body.

Thyroid hormone inhibits thyroid hormone receptorexpression (TRE on THR genes).

of Thyroid Hormone Receptors

One Major Target Gene of T3:

Th S di /P i ATP P


89/99

Pumps sodium and potassium across cell membranes tomaintain resting membrane potential

Activity of the Na+/K+pump uses up energy, in the form ofATP

About 1/3rd of all ATP in the body is used by the Na+/K+ATPase

T3 increases the synthesis of Na+/K+pumps, markedlyincreasing ATP consumption.

T3 also acts on mitochondria to increase ATP synthesis

The resulting increased metabolic rate increases

thermogenesis (heat production).

The Sodium/Potassium ATPase Pump

Thyroid Hormone Deficiency: Hypothyroidism


90/99

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 TBG.)

How is Hypothyroidism Related to Goiter?


91/99

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.

yp y

Thyroid Hormone Excess: Hyperthyroidism


92/99

Emotional symptoms (nervousness, irritability), fatigue,

heat intolerance, elevated metabolic rate, weight loss,

tachycardia, goiter, muscle wasting, apparent bulging of

eyes, may develop congestive heart failure.

Also due to many causes (excessive TSH release,

autoimmune disorders,)

Thyroid Hormone Excess: Hyperthyroidism


93/99

Graves' disease:A condition usually caused by

excessive production of thyroid hormone and

characterized by an enlarged thyroid gland,

protrusion of the eyeballs, a rapid heartbeat, and

nervous excitability. Also called exophthalmic

goiter.

a thioamide drug used to treat hyperthyroidism


94/99

Regulates of Basal Metabolic Rate (BMR).

Increases oxygen consumption in most target tissues.

Permissive actions: TH increases sensitivity of target

tissues to catecholamines, thereby elevating lipolysis,

glycogenolysis, and gluconeogenesis.

a thioamide drug used to treat hyperthyroidism

GLAND THYROID


95/99

GLAND THYROID

Terletak di leher bagian depan, di samping kiridan kanan trakea.

Kelenjar tyroid menghasilkan 3 jenis hormon :

T3 (triiodotironin)

T4 (tetraiodotironin)

Tyrokalsitonin


96/99

Bahan dasar pembtkan hormon adalah

yodium yang diperoleh dari mknan danminuman

Fungsi kel tyroid :

Mengatur keg metabolik Merangsang oksidasi

Mengatur penggunaan O2 dan pengeluaran

CO2 Mempengaruhi perkemb susunan saraf

Merangsang pertumbuhan

GLAND PARATYROID


97/99

GLAND PARATYROID

Menempel pada bagian anterior dan posteriorkedua lobus kelenjar tyroid, menghasilkanhormon paratiroksin.

Fungsi hormon paratyroid : Meningkatkan kadar Ca dan menurunkan kadar

fosfat

Meningkatkan resorbsi tulang shg serum Ca

meningkat Organ target PTH tulang, ginjal dan usus halus


98/99

Parameter T3 T4


99/99

Production rate (nmol/day) 50 110

Fraction from thyroid 0.2 1

Relative metabolic potency 1 0.3 Serum concentration Total (nmol/L) 1.8 100

Free (pmol/L) 5 20

Distribution volume (L) 40 10

Fraction intracellular 0.64 0.15

Half-life (days) 0.75 6.7

Documents

K4A - Fisiologi Tiroid