BBDM KASUS

30 Maret 2015
Diskusi Pakar

Seorang wanita 40 tahun, datang ke

Puskesmas dengan keluhan benjolan di
leher.Berat badan pasien turun meski
nafsu makan meningkat.Pasien juga
sering kelelahan, selalu kegerahan
meski cuaca tidak panas, haid tidak
teratur.Dari pemeriksaan fisik
ditemukan exoftalmus, tremor, dan
atrofi otot lengan.Pasien berasal dari
daerah pegunungan.

Mengapa hormon T3 lebih aktif dari pada

hormon T4 padahal strukturnya lebih
sederhana?
Ratio T4 : T3 - 20:1 (3x potencyT4)
T4 deiodinases (5'-iodinase).
decarboxylation & deiodination to
iodothyronamine (T1a)
& thyronamine (T0a).
All three isoforms of the deiodinases
are selenium-containing enzymes, thus dietary
selenium is essential for T3production.

The major part of thyroxine

deiodination occurs within the cells.
Deionidase 2 activity can be regulated by ubiquitination:
The covalent attachment of ubiquitine inactivates D2 by
disrupting dimerization and targets it to degradation in
the proteosome
Deubiquitination removing ubiquitin from D2 restores its
activity and prevents proteosomal degradation.
The Hedgehog cascade acts to increase D2 ubiquitination
through WSB1 activity, decreasing D2 activity.[
D-propranolol inhibits thyroxine deiodinase, thereby
blocking the conversion of T4 to T3, providing some though
minimal therapeutic effect

Deiodoninase function
Deiodinases can either activate or inactivate thyroid
hormones:
Activation occurs by conversion of the prohormone
thyroxine (T4) to the active hormone triiodothyronine (T3)
through the removal of an iodine atom on the outer ring.
Inactivation of thyroid hormones occurs by removal of
an iodine atom on the inner ring, which converts thyroxine to
the inactivereverse triiodothyronine (rT3), or which converts
the active triiodothyronine to diiodothyronine (T2).

The major secreted product of the thyroid gland is T4 while T3 is secreted

only in small amounts and derives mainly from the peripheral
deiodination of T4.
One third of circulating T4 is converted to T3 in peripheral tissues. Both
hormones are present in serum either bound to proteins or in the free
state.
T3 is less tightly bound to plasma proteins than is T4 and is therefore
more readily available for cellular uptake.
The free hormone is biologically active and interacts with specific
receptors localized in the membrane, mitochondria, cytoplasm and
nucleus of responsive cells. T3 binds to nuclear receptors to a much
greater extent than T4, hence T3 is more rapidly and biologically active
than T4. T3 and T4 are deiodinated and deaminated in the tissues. In the
liver, they are conjugated, pass into the bile and are excreted into the
intestine. Conjugated and free hormones are also excreted by the
kidney.

Tipe

Lokasi

Fungsi

type I (DI)

Hepar ginjal

Deiodonisasi kedua cincin

type II
deiodinase
(DII)

jantung, otot
skelet, lemak,
tiroid dan
hipofisis

DII dapat deiodonisasi cincin luar

prohormon tiroksin dan enzim
utaman aktivasi. reverse
triiodothyronine didegradasi oleh DII

type III
deiodinase
(DIII)

Plasenta
DIII dapat deiodonisasi cincin dalam
jaringan janin, di tiroksin dan triiodotironin dan
otak kecuali
merupakan enzim inaktivasi utama
hipofisis

Jika enzim yang digunakan dalam proses biosintesis

tiroid rusak apakah ada enzim pengganti sehingga
sintesis tiroid tetap berlangsung.

When the iodotyrosine enzyme system is

defective MIT and DIT escape in large amounts
from the thyroid gland into the blood and
thence into the urine taking their iodine with
them.

The colloid droplets next fuse with lysosome vesicles

which contain proteolyticenzymes. The proteases
help digest the thyroglobulin molecule releasing T4,
T3, DIT and MIT into the cytoplasm.
While T4 and T3 diffuse via the basal surface into the
blood stream, the MIT and DIT get rapidly
deiodinated by enzymedeiodinase. This mechanism
helps retrieve iodide for recycling along with tyrosine
for recycling

 In both these families genetic studies showed

that the defect was transmitted as an
autosomal recessive characteristic; some of
the apparently unaffected relatives were
shown to have minor defects in the
deiodination of MIT.