BBDM KASUS

30 Maret 2015Diskusi Pakar

Seorang wanita 40 tahun, datang kePuskesmas dengan keluhan benjolan dileher.Berat badan pasien turun meskinafsu makan meningkat.Pasien jugasering kelelahan, selalu kegerahanmeski cuaca tidak panas, haid tidakteratur.Dari pemeriksaan fisikditemukan exoftalmus, tremor, danatrofi otot lengan.Pasien berasal daridaerah 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 deiodinasesare selenium-containing enzymes, thus dietary selenium is essential for T3production.

The major part of thyroxinedeiodination 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 ubiquitinationthrough 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 luarprohormon tiroksin dan enzimutaman aktivasi. reverse triiodothyronine didegradasi oleh DII

type III deiodinase(DIII)

Plasenta jaringan janin, di otak kecuali hipofisis

DIII dapat deiodonisasi cincin dalamtiroksin dan triiodotironin danmerupakan enzim inaktivasi utama

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.