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Gangguan Fungsi

Tiroid

Oleh :
Eli Halimah

FUNGSI
Fungsi Kelenjar Tiroid :
Pengikat Iodida
Sintesis hormon tiroid
Penyimpanan hormon tiroid
Fungsi Hormon Tiroid :
Mengatur kecepatan metabolisme

tubuh
Mengatur produksi panas
Mengatur pelepasan energi dalam
otot
Mengatur pertumbuhan dan
diferensiasi

Structure of the thyroid follicle

The Thyroid Produces and


Secretes 2 Metabolic
Hormones
Two principal hormones
Thyroxine (T4 ) and

triiodothyronine (T3)
Required

for homeostasis of all

cells
Influence cell differentiation,
growth, and metabolism
Considered the major metabolic
hormones because they target
virtually every tissue

Thyroid-StimulatingHormone
(TSH)
Regulates

production,
growth

thyroid hormone
secretion,
and

Is regulated by the negative

feedback action of T4 and T3

Biosynthesis of T4 and T3
The process includes
Dietary iodine (I) ingestion
Active transport and uptake of
iodide (I) by thyroid gland
Oxidation of I- and iodination of
thyroglobulin (Tg) tyrosine residues
Coupling of iodotyrosine residues
(MIT and DIT) to form T4 and T3
Proteolysis of Tg with release of T4

and T3 into the circulation

Iodine Sources
Available through certain foods

(eg, seafood, bread, dairy


products), iodized salt, or dietary
supplements, as a trace mineral
The recommended minimum

intake is 150 g/day

Sintesis Hormon
Tiroid

THYROID HORMONES
OH

OH

I
O

O
NH2

Thyroxine (T4)

OH

NH2

OH

3,5,3-Triiodothyronine (T3)

FEEDBACK REGULATION
THE HYPOTHALAMIC-PITUITARYTHYROID AXIS

Hormones derived from the


pituitary that regulate the
synthesis and/or secretion of
other hormones are known as
trophic hormones.
Key players for the thyroid include:
TRH - Thyrophin Releasing Hormone
TSH - Thyroid Stimulating Hormone
T4/T3 - Thyroid hormones

PITUITARY-THYROID AXIS

HM Goodman, BASIC MEDICAL ENDOCRINOLOGY 3rd Ed.

Mekanisme Pengaturan
Tiroid

Hypothalamic-Pituitary-Thyroid Axis
Negative Feedback Mechanism

TSH REGULATION OF
THYROID FUNCTION
TSH binds to specific cell surface

receptors that stimulate adenylate


cyclase to produce cAMP.
TSH increases metabolic activity

that is required to synthesize


Thyroglobulin (Tg) and generate
peroxide.
TSH stimulates both I- uptake and

iodination of tyrosine resides on


Tg.

ION TRANSPORT BY THE


THYROID FOLLICULAR CELL
ClO4-, SCN-

BLOOD
I-

organification

NaI symporter (NIS)


Thyroid peroxidase (TPO)

COLLOID

Propylthiouracil
(PTU) blocks
iodination of
thyroglobulin

THYROGLOBULIN SYNTHESIS IN THE


THYROID FOLLICULAR CELL
Iodination of
Tyr residues of Tg

COLLOID

TSH
TSH receptor
TPO

THYROID HORMONE SECRETION BY


THE THYROID FOLLICULAR CELL

T4
T3

COLLOID
DIT
MIT

TSH
TSH receptor

I-

THYROID HORMONES
IN THE BLOOD
Approximately 99.98% of T4 is

bound to 3 serum proteins:


Thyroid binding globulin (TBG)
~75%;
Thyroid binding prealbumin (TBPA
or transthyretin) 15-20%;
albumin ~5-10%
Only ~0.02% of the total T4 in blood is
unbound or free.
Only ~0.4% of total T3 in blood is free.

BASICS OF THYROID HORMONE


ACTION IN THE CELL

SPECIFIC ACTIONS OF
THYROID HORMONE:
METABOLIC
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.

SPECIFIC ACTIONS OF
THYROID HORMONE:
DEVELOPMENT
TH is critical for normal development

of the skeletal system and musculature.


TH is also essential for normal brain

development
and
regulates
synaptogenesis, neuronal integration,
myelination and cell migration.
Cretinism

is the term for the


constellation of defects resulting from
untreated neonatal hypothyroidism.

Risk factors for thyroid disease


personal history of thyroid disease
strong family history of thyroid

disease
diagnosis of autoimmune disease
past history of neck irradiation
drug therapies such as lithium and
amiodarone
women over age 50
elderly patients
women 6 weeks to 6 months postpartum

Signs/Symptoms
Hypothyroidism

Weight gain
Hair loss
Lethargy
Menstrual irregularities
(menorrhagia)
Cognitive impairment
Depression
Constipation
Goitre
Dry skin
Cold intolerance

Hyperthyroidism

Weight loss
Hair loss
Palpitations /
Tachycardia / Atrial
fibrillation
Menstrual irregularities
(amenorrhea/oligomenorrh
ea)
Widened pulse pressure
Nervousness and tremor
Muscular weakness
Goitre
Heat intolerance,
diaphoresis, clammy hands
Hypertension

Causes of high thyroidstimulating hormone (TSH)


Hypothyroidism
Recovery from severe illness
Pituitary excess due to

pituitary tumours causing


secondary hyperthyroidism
(very rare)

Causes of low
thyroid-stimulating hormone (TSH)
1. Hyperthyroid State
a. Both T3 and T4 elevated
Graves' disease
Toxic multinodular goiter
b. Only T3 elevated with normal T4
T3 toxicosis (e.g. Autonomous nodule)
Exogenous T3 ingestions (liothyronine)
c. Only T4 elevated with normal T3
Hyperthyroidism patient with nausea,
vomiting and starvation causing decreased
conversion of T4 to T3
2. Hypothyroid State
Pituitary or hypothalamic disease (both T4 and
T3 low)
3. Euthyroid State
Sick euthyroid (both T3, T4 low, rT3* elevated)
Drugs such as glucocorticoids, octreotide, and
dopamine

TSH

Low

High

FT4 & FT3

FT4

Low

Low

High

1 Hypothyroid
2 thyrotoxicosis

If
equivocal

Central
1 Thyrotoxic
Hypothyr
oid
TRH Stim.

Endo consult
FT3, rT3
MRI, -SU

High

MRI, etc.

RAIU

A) 1 Hypothyroidism
B) Central Hypothyroidism
C) Euthyroid
D) 1 Thyrotoxicosis

Thyroid Function Tests


TSH

0.4 5.0 mU/L

Free T4 (thyroxine) 9.1 23.8 pM


Free T3 (triiodothyronine) 2.23-5.3 pM

Hypothyroidism
Hypothyroidism is a disorder

with multiple
causes in which the thyroid fails
to
secrete an adequate amount of
thyroid hormone
The most common thyroid disorder
Usually caused by primary thyroid

gland failure
Also may result from diminished

stimulation of the thyroid gland by


TSH

Hyperthyroidism
Hyperthyroidism

refers to
excess synthesis and secretion
of thyroid hormones by the
thyroid gland, which results in
accelerated metabolism in
peripheral tissues

Typical Thyroid Hormone


Levels in Thyroid Disease
TSH

Hypothyroidism
Low
Hyperthyroidism
High

High

T4

T3

Low
Low

High

EXAMPLES OF THYROID DISEASES

1 Hypothyroidism

Hyperthyroidism

www.hsc.missouri.edu/~daveg/thyroid/thy_dis.html

EXAMPLES OF THYROID DISEASES

Juvenile Hypothyroidism Congenital Hypothyroidism