TUTOR   IMUNOLOGI<br />PEMERIKSAAN HORMON TIROID (T3, T4, TSH, fT4)<br />Lestari Ekowati,dr.<br />SitiRochmatoenHarmadji, ...
PENDAHULUAN<br />TUTOR  IMUNOLOGI<br />2<br />Kelainankelenjartiroid<br />mempelajaridanmendiagnosis  :<br /><ul><li>Axis ...
hormon yang bekerjapada axis tersebut
pengaruhpada organ lainnya
pengaruhluarterhadap axis tersebut</li></ul>kelainanendokrin<br />terseringkedua<br />setelah diabetes mellitus<br />berpe...
HORMON TIROID<br />TUTOR  IMUNOLOGI<br />3<br />Ada 2 :<br />1. Tiroksin (Thyroxine = T4 = L-3,5,3’,5’-tetraiodothyronin) ...
Pengaruhfisiologishormontiroid<br />TUTOR  IMUNOLOGI<br />4<br />
Pengaturanhormontiroid<br />TUTOR  IMUNOLOGI<br />5<br />
Mekanismeumpanbalik<br />TUTOR  IMUNOLOGI<br />6<br />
KELAINAN TIROID<br />TUTOR  IMUNOLOGI<br />KELAINAN TIROID<br />HIPOTIROID<br />GOITER<br />HIPERTIROID<br />EUTIROID<br /...
TUTOR  IMUNOLOGI<br />Th 70-an<br />Th 80-an<br />8<br />Radioimmunoassay (RIA)<br />Immunoradiometric assay (IRMA)<br />E...
RADIOIMMUNOASSAY (RIA)<br />TUTOR  IMUNOLOGI<br />9<br /><ul><li>DitemukanolehYallow and Bersonpadaakhirtahun 1950
MenggunakanRadioaktifsebagai label, seperti : 131I, 125I, 3H
Prinsipkompetitif : analit yang dideteksiberkompetisidengananalit yang berlabelradioaktifuntukberikatandenganantibodi</li>...
IMMUNORADIOMETRIC ASSAY (IRMA)<br />TUTOR  IMUNOLOGI<br />10<br />Prinsip : ikatan non-kovalenreversibelantara antigen dan...
ENZYME IMMUNOASSAY (EIA)<br /> TUTOR  IMUNOLOGI<br />11<br />Menggunakanenzimsebagai label :<br /><ul><li>horseradish pero...
 glucose-6-phosphate-dehydrogenase
 alkaline phosphatase
 ß-D-galactosidase</li></ul>EIA pertama kali menggunakanprinsipkompetitifsepertipada RIA<br />
ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA) <br />TUTOR  IMUNOLOGI<br />12<br />Bagiandari EIA<br />Non kompetitif EIA<br />...
ELECTROCHEMILUMINESCENT ASSAY (ECLIA)<br />13<br /><ul><li>Emisicahayaakibatreaksielektrokimia, biasanyareaksiredoks, meng...
Molekul yang seringdigunakansebagaichemiluminescense : luminol, acridium esters, ruthenium derivativesdannitrophenyl oxalate.
Paling sensitifdibanding RIA dan EIA.
Reagenstabildan non toksik.</li></ul>TUTOR  IMUNOLOGI<br />
Pengambilansampel<br />TUTOR  IMUNOLOGI<br />Tidakperlu<br />persiapankhusus<br />Bahan : serum, plasma <br />EDTA atau he...
PEMERIKSAAN HORMON TIROID DI LAB. PK RSUD DR SOETOMO SURABAYA<br />TUTOR  IMUNOLOGI<br />T3, T4, TSH, fT4<br />Senin, Rabu...
PEMERIKSAAN T3 <br />TUTOR  IMUNOLOGI<br />Varian <br />tirotoksik :<br />kadar T3 ↑,<br />T4 normal<br />(T3 <br />tiroto...
Prinsippemeriksaan T3<br />TUTOR  IMUNOLOGI<br />1<br />17<br />EIA Kompetitif<br />Goat anti-mouse IgG<br />T3 conjugate<...
Prosedurpemeriksaan T3<br />TUTOR  IMUNOLOGI<br />18<br />50 µL<br />Standar/<br />Sampel/<br />Kontrol<br />Campur<br />r...
Penghitunganhasil<br />TUTOR  IMUNOLOGI<br />19<br />Absorbans<br />Dihitung rata-rata absorbansuntuktiap set standar, kon...
TUTOR  IMUNOLOGI<br />20<br />Range normal : 0,6-1,85 ng/mL.<br />Kadar T3 total dalam serum parareldengan TBG<br />Pening...
Keterbatasanprosedur<br />21<br />Hasil yang benar&akuratdiperolehjikaprosedurpemeriksaandilakukansesuaiinstruksi<br />Pro...
PEMERIKSAAN T4<br />TUTOR  IMUNOLOGI<br />disintesisdandisimpandalamkelenjartiroid<br />>99% terikat, pada :<br /><ul><li>...
Thyroxine binding pre albumin (TBPA) 20%
Albumin 10%</li></ul>0,03% dalamkeadaantidakterikat.<br />ProteolisisThyroglobulinakan<br />melepaskan T4 kedalamalirandar...
Prinsippemeriksaan T4<br />TUTOR  IMUNOLOGI<br />23<br />EIA Kompetitif<br />Antibodi Anti T4<br />T4 conjugate<br />Sampe...
Prosedurpemeriksaan T4<br />TUTOR  IMUNOLOGI<br />24<br />25 µL<br />Standar/<br />Sampel/<br />Kontrol<br />Campur<br />R...
25<br />Kadar T4 normal : 5,0 -13,0 ng/mL<br />Sebaiknyasetiaplaboratoriummenentukankadarnyasendiridisesuaikandengangeogra...
PEMERIKSAAN TSH<br />TUTOR  IMUNOLOGI<br />B<br />A<br />C<br />D<br />E<br />26<br />disekresiolehlobus anterior kelenjar...
TUTOR  IMUNOLOGI<br />27<br />TSH, LH, FSH, danhCG, memilikirantaialpha yang identik.<br />Rantaibetaberbedanamunmengandun...
Prinsippemeriksaan TSH<br />TUTOR  IMUNOLOGI<br />28<br />ELISA  SANDWICH<br />Antibodi Anti-TSH<br />(murine)<br />Antibo...
Prosedurpemeriksaan TSH<br />TUTOR  IMUNOLOGI<br />29<br />100 µL<br />Working conjugate reagen<br />Campur rata<br />30 ‘...
TUTOR  IMUNOLOGI<br />30<br />Kadar TSH normal : 0,4 -6,0 µIU/mL<br />Kadar TSH >10 µIU/mL : hipotiroidisme primer<br />Ka...
PEMERIKSAAN FREE T4<br />TUTOR  IMUNOLOGI<br />31<br />T4 berikatandengan protein serum<br />Hanya 0,03% T4 yang bebas, di...
Prinsippemeriksaan fT4<br />TUTOR  IMUNOLOGI<br />32<br />EIA Kompetitif<br />AntibodiAnti-fT4<br />fT4 conjugate<br />Sam...
Prosedurpemeriksaan fT4<br />TUTOR  IMUNOLOGI<br />33<br />50 µL<br />Standar/<br />Sampel/<br />Kontrol<br />Inkubasi<br ...
TUTOR  IMUNOLOGI<br />1<br />2<br />3<br />4<br />fT4 dapatmemberikanpenilaian yang lebihakuratuntukpenilaian status tiroi...
Thank You !<br />www.themegallery.com<br />
NORMAL VALUE<br />TUTOR  IMUNOLOGI<br />
TUTOR  IMUNOLOGI<br />
Kurvastandar TSH<br />TUTOR  IMUNOLOGI<br />absorbans<br />Konsentrasi TSH µIU/mL<br />
Obat yang mempengaruhitiroid<br />Dopamine : mengurangisekresi TSH<br />Glukokortikoid : mengurangisekresi TSH<br />Lithiu...
Pemantauanterapi<br />TUTOR  IMUNOLOGI<br />Perubahan TSH serum lambat, butuhwaktubeberapabulanuntukkembalikerentang norma...
interferensi<br />Reaksisilang<br />Antibodianalit endogen<br />Antibodiheterofilik<br />Interaksiobat<br />	Heparin meran...
TSH <br />Anaklahir 4 hari 1.0-39.0 mIU/L<br />2-20 minggu       1.7-9.1<br />21 minggu-20th  0.7-64.0 <br />Dewasa 21-54t...
T4 <br />Neonatus > 6.5 ug/dL<br />Dewasa 4.6-11.0<br />T3 <br />Dewasa 20-50 tahun 70-204 ng/dL<br />   50-90 tahun 40-18...
Thyroxine<br />TUTOR  IMUNOLOGI<br /><ul><li>= 3,5,3',5'-tetraiodothyronine (T4) : major thyroid hormones secreted by the ...
synthesized via the iodination and covalent bonding of the phenyl portions of tyrosine residues found in an initial peptid...
These iodinated diphenyl compounds are cleaved from their peptide backbone upon being stimulated by thyroid-stimulating ho...
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  1. 1. TUTOR IMUNOLOGI<br />PEMERIKSAAN HORMON TIROID (T3, T4, TSH, fT4)<br />Lestari Ekowati,dr.<br />SitiRochmatoenHarmadji, dr., SpPK(K)<br />Selasa, 22 Maret 2011<br />
  2. 2. PENDAHULUAN<br />TUTOR IMUNOLOGI<br />2<br />Kelainankelenjartiroid<br />mempelajaridanmendiagnosis :<br /><ul><li>Axis Hipotalamus- Hipofisis-Tiroid
  3. 3. hormon yang bekerjapada axis tersebut
  4. 4. pengaruhpada organ lainnya
  5. 5. pengaruhluarterhadap axis tersebut</li></ul>kelainanendokrin<br />terseringkedua<br />setelah diabetes mellitus<br />berpengaruhkehampir<br />seluruhtubuh<br />
  6. 6. HORMON TIROID<br />TUTOR IMUNOLOGI<br />3<br />Ada 2 :<br />1. Tiroksin (Thyroxine = T4 = L-3,5,3’,5’-tetraiodothyronin) <br />2. Triiodothyronine (T3 = L-3,5,3’-triiodothyronine)<br />Kuantitatifterbanyak : T4 <br />T3 sedikit, tapiaktifsecarabiologis<br /> (potensi 3 x T4)<br />T4 sebagaiprecursor / prohormon<br />Biladiperlukanakandipecahdi<br />jaringanuntukmembentuk T3<br />
  7. 7. Pengaruhfisiologishormontiroid<br />TUTOR IMUNOLOGI<br />4<br />
  8. 8. Pengaturanhormontiroid<br />TUTOR IMUNOLOGI<br />5<br />
  9. 9. Mekanismeumpanbalik<br />TUTOR IMUNOLOGI<br />6<br />
  10. 10. KELAINAN TIROID<br />TUTOR IMUNOLOGI<br />KELAINAN TIROID<br />HIPOTIROID<br />GOITER<br />HIPERTIROID<br />EUTIROID<br />OBAT<br />DIFUS<br />NODULAR<br />UNI<br />NODULAR<br />MULTI<br />NODULAR<br />7<br />KLINIS<br />SUB <br />KLINIS<br />KLINIS<br />SUB <br />KLINIS<br />
  11. 11. TUTOR IMUNOLOGI<br />Th 70-an<br />Th 80-an<br />8<br />Radioimmunoassay (RIA)<br />Immunoradiometric assay (IRMA)<br />Enzyme immunoassay (EIA)<br />Enzyme-linked immunoassay (ELISA)<br />PEMERIKSAAN HORMON TIROID<br />Electrochemiluminescent assay<br />(ECLIA)<br />
  12. 12. RADIOIMMUNOASSAY (RIA)<br />TUTOR IMUNOLOGI<br />9<br /><ul><li>DitemukanolehYallow and Bersonpadaakhirtahun 1950
  13. 13. MenggunakanRadioaktifsebagai label, seperti : 131I, 125I, 3H
  14. 14. Prinsipkompetitif : analit yang dideteksiberkompetisidengananalit yang berlabelradioaktifuntukberikatandenganantibodi</li></ul>Antibodipada<br />fasepadat<br />Ag berlabelradioaktif<br />Ag takberlabel (sampel)<br />Ikatan Ag-Abspesifik<br />
  15. 15. IMMUNORADIOMETRIC ASSAY (IRMA)<br />TUTOR IMUNOLOGI<br />10<br />Prinsip : ikatan non-kovalenreversibelantara antigen danantibodispesifik yang dilabeldenganradioaktif<br />Antibodipadafasepadat<br />Antibodiberlabelradioaktif<br />Ikatan Ag-Abspesifik<br />Sampel<br />
  16. 16. ENZYME IMMUNOASSAY (EIA)<br /> TUTOR IMUNOLOGI<br />11<br />Menggunakanenzimsebagai label :<br /><ul><li>horseradish peroxidase
  17. 17. glucose-6-phosphate-dehydrogenase
  18. 18. alkaline phosphatase
  19. 19. ß-D-galactosidase</li></ul>EIA pertama kali menggunakanprinsipkompetitifsepertipada RIA<br />
  20. 20. ENZYME-LINKED IMMUNOSORBENT ASSAY (ELISA) <br />TUTOR IMUNOLOGI<br />12<br />Bagiandari EIA<br />Non kompetitif EIA<br />Lebihsensitif<br />(<1 pg/mL)<br />Indirek: reagenberlabelenzym<br />tidakikutbereaksipadaikatan Ag-Abawal<br />Sandwich = capture : <br />jikaAb yang dilekatkanpadafasepadat<br />
  21. 21. ELECTROCHEMILUMINESCENT ASSAY (ECLIA)<br />13<br /><ul><li>Emisicahayaakibatreaksielektrokimia, biasanyareaksiredoks, menghasilkaneksitasimolekul yang kembalike ground state.
  22. 22. Molekul yang seringdigunakansebagaichemiluminescense : luminol, acridium esters, ruthenium derivativesdannitrophenyl oxalate.
  23. 23. Paling sensitifdibanding RIA dan EIA.
  24. 24. Reagenstabildan non toksik.</li></ul>TUTOR IMUNOLOGI<br />
  25. 25. Pengambilansampel<br />TUTOR IMUNOLOGI<br />Tidakperlu<br />persiapankhusus<br />Bahan : serum, plasma <br />EDTA atau heparin<br />Tidakperlumerubah<br />polamakan & aktifitasfisik<br />Disimpan 2-8oC, 3-5 hari<br />Beku : stabilsampai ± 30 hari<br />Obatberhentisampaites<br />selesaidikerjakan<br />Tidakhemolisisataulipemik<br />Adajugaobat-obatan yang tetapdimintauntukdiminumkarenaingindiketahuipengaruhnya<br />9<br />14<br />
  26. 26. PEMERIKSAAN HORMON TIROID DI LAB. PK RSUD DR SOETOMO SURABAYA<br />TUTOR IMUNOLOGI<br />T3, T4, TSH, fT4<br />Senin, Rabu, Jum’at<br />EIA, Thyrolisa, (Indec-Diagnostic)<br />15<br />
  27. 27. PEMERIKSAAN T3 <br />TUTOR IMUNOLOGI<br />Varian <br />tirotoksik :<br />kadar T3 ↑,<br />T4 normal<br />(T3 <br />tirotoksikosis)<br />Peningkatan T3 tanpapeningkatan T4 : <br />gejalaawaltirotoksikosisrekurenpada<br />pasien yang mendapatterapi<br />16<br />T4 dan T3 <br />sebagianbesar<br />terikatpada<br />Thyroxine<br />Binding <br />Globuline<br />(TBG)<br />Konsentrasi T3 <<< T4<br />Potensimetabolik T3 >>><br />
  28. 28. Prinsippemeriksaan T3<br />TUTOR IMUNOLOGI<br />1<br />17<br />EIA Kompetitif<br />Goat anti-mouse IgG<br />T3 conjugate<br />Mouse Ab anti-T3<br />Sampel<br />
  29. 29. Prosedurpemeriksaan T3<br />TUTOR IMUNOLOGI<br />18<br />50 µL<br />Standar/<br />Sampel/<br />Kontrol<br />Campur<br />rata<br />30 ‘’<br />Campur<br />Rata 30 ‘’<br />Microwells<br />100 µL<br />Working conjugate reagen<br />50 µL<br />ReagenAntibodi<br />Inkubasi<br />Suhukamar<br />60’<br />Campur rata 30 ‘’<br />Inkubasi<br />Suhukamar<br />20’<br />Buang<br />Cuci-bilas<br />5 x<br />Hilangkansisa air dg absorbent paper<br />Baca OD pada 450 nm dalam 15’<br />100 µL<br />Substrate solution<br />100 µL<br />Stop solution<br />
  30. 30. Penghitunganhasil<br />TUTOR IMUNOLOGI<br />19<br />Absorbans<br />Dihitung rata-rata absorbansuntuktiap set standar, kontrol, sampel<br />Konsentrasi (ng/mL)<br />Konsentrasi T3 ditentukandenganmemasukkannilaiabsorbanstiapsampelkedalamkurvastandar.<br />
  31. 31. TUTOR IMUNOLOGI<br />20<br />Range normal : 0,6-1,85 ng/mL.<br />Kadar T3 total dalam serum parareldengan TBG<br />Peningkatankadar T3 dapatterjadipada<br />penderitahipotiroid yang sedangmendapatkanterapi<br />Konsentrasi minimal yang dapatterdeteksi :<br />0,2 ng/mL.<br />
  32. 32. Keterbatasanprosedur<br />21<br />Hasil yang benar&akuratdiperolehjikaprosedurpemeriksaandilakukansesuaiinstruksi<br />Prosedurpencuciansangatpenting. Pencucian yang tidakbenarakanmenghasilkanpresisi yang burukdanpembacaanabsorbans yang tinggipalsu.<br />Sampel serum yang lipemik, hemolisisataukeruhtidakdapatdiperiksa.<br />Hasil yang diperolehharusdigunakanbersamadenganprosedur diagnosis daninformasilainnya<br />TUTOR IMUNOLOGI<br />
  33. 33. PEMERIKSAAN T4<br />TUTOR IMUNOLOGI<br />disintesisdandisimpandalamkelenjartiroid<br />>99% terikat, pada :<br /><ul><li>Thyroxine binding globulin (TBG) 70%
  34. 34. Thyroxine binding pre albumin (TBPA) 20%
  35. 35. Albumin 10%</li></ul>0,03% dalamkeadaantidakterikat.<br />ProteolisisThyroglobulinakan<br />melepaskan T4 kedalamalirandarah<br />22<br />T4 total : skrininggangguantiroid<br />T4 ↑ : hipertiroidisme<br />T4 ↓ : hipotiroidisme<br />Text<br />T4<br />Text<br />
  36. 36. Prinsippemeriksaan T4<br />TUTOR IMUNOLOGI<br />23<br />EIA Kompetitif<br />Antibodi Anti T4<br />T4 conjugate<br />Sampel<br />
  37. 37. Prosedurpemeriksaan T4<br />TUTOR IMUNOLOGI<br />24<br />25 µL<br />Standar/<br />Sampel/<br />Kontrol<br />Campur<br />Rata 30 ‘’<br />Inkubasi<br />Suhukamar<br />60’<br />Microwells<br />100 µL<br />Working conjugate reagen<br />Campur rata 30 ‘’<br />Buang<br />Cuci-bilas<br />5 x<br />100 µL<br />Substrate solution<br />Hilangkansisa air dg absorbent paper<br />Inkubasi<br />Suhukamar<br />20’<br />100 µL<br />Stop solution<br />Baca OD <br />450 nm, 15’<br />
  38. 38. 25<br />Kadar T4 normal : 5,0 -13,0 ng/mL<br />Sebaiknyasetiaplaboratoriummenentukankadarnyasendiridisesuaikandengangeografisdanpopulasi yang ada<br />Konsentrasi minimal yang dapatterdeteksiadalah 0,4 ng/mL.<br />TUTOR IMUNOLOGI<br />
  39. 39. PEMERIKSAAN TSH<br />TUTOR IMUNOLOGI<br />B<br />A<br />C<br />D<br />E<br />26<br />disekresiolehlobus anterior kelenjarhipofisis(pituitary)<br />mempengaruhiproduksidanpelepasan T3 dan T4 darikelenjartiroid<br />sensitifuntukmendiagnosishipotiroidisme primer atausekunder<br />TSH<br />glikoprotein, <br />BM ± 28.000 dalton<br />terdiridari 2 subunit : alphadanbeta.<br />
  40. 40. TUTOR IMUNOLOGI<br />27<br />TSH, LH, FSH, danhCG, memilikirantaialpha yang identik.<br />Rantaibetaberbedanamunmengandungregiodenganurutanasam amino yang identik.<br />Regio yang homolog inidapatmenyebabkanreaksisilang(cross reaction) denganbeberapaantisera TSH poliklonal. <br />Kadar TSH sangatrendah, namunsangatpentinguntukmengaturfungsitiroid yang normal.<br />Pelepasan TSH diaturolehTSH-releasing hormone (TRH) yang diproduksiolehhipotalamus.<br />Kadar TSH dan TRH berbandingterbalikdengankadarhormontiroid.<br />
  41. 41. Prinsippemeriksaan TSH<br />TUTOR IMUNOLOGI<br />28<br />ELISA SANDWICH<br />Antibodi Anti-TSH<br />(murine)<br />Antibodi Anti TSH (goat)<br />Sampel<br />
  42. 42. Prosedurpemeriksaan TSH<br />TUTOR IMUNOLOGI<br />29<br />100 µL<br />Working conjugate reagen<br />Campur rata<br />30 ‘’<br />Inkubasi<br />Suhukamar<br />60’<br />100 µL<br />Standar/<br />Sampel/<br />Kontrol<br />Microwells<br />Inkubasi<br />Suhukamar<br />20’<br />Campur rata 30 ‘’<br />Buang<br />Cuci-bilas<br />5 x<br />100 µL<br />TMB Substrate solution<br />Hilangkansisa air dg absorbent paper<br />100 µL<br />Stop solution<br />Baca OD <br />450 nm, 15’<br />
  43. 43. TUTOR IMUNOLOGI<br />30<br />Kadar TSH normal : 0,4 -6,0 µIU/mL<br />Kadar TSH >10 µIU/mL : hipotiroidisme primer<br />Kadar TSH rendah/tidakterdeteksi/normal : indikatorhipotiroidismesekunder<br />(kegagalansekresi TSH atau TRH)<br />Kadar rendah : hipersekresi T3 dan T4 <br />padaGrave’s diseaseatautiroiditis<br />DD : memeriksakadar TSH dan fT4 <br />dalam serum secarasimultan<br />Konsentrasimin.yangterdeteksi : 0,2 µIU/mL.<br />
  44. 44. PEMERIKSAAN FREE T4<br />TUTOR IMUNOLOGI<br />31<br />T4 berikatandengan protein serum<br />Hanya 0,03% T4 yang bebas, disebutsebagaiFree T4 (fT4), merupakanmetabolikaktif<br />Hipertiroidisme primer <br />-> produksi T4 >><br />-> kadar fT4 >><br />Hipotiroidisme primer -> produksi T4 <<br /> -> kadar fT4 <<br />Kadar T4 total tergantungkadar TBG <br />Kadar TBG dipengaruhioleh : obat, hormon steroid, kehamilan, danpenyakit non tiroid. <br />Pemeriksaan fT4 : untukmengetahuikeseimbangan<br />antara T4 bebasdan T4 yang terikat TBG<br />Metodeinidapatmenggambarkan status tiroidsecaraumumdengansatumacampemeriksaan.<br />
  45. 45. Prinsippemeriksaan fT4<br />TUTOR IMUNOLOGI<br />32<br />EIA Kompetitif<br />AntibodiAnti-fT4<br />fT4 conjugate<br />Sampel<br />
  46. 46. Prosedurpemeriksaan fT4<br />TUTOR IMUNOLOGI<br />33<br />50 µL<br />Standar/<br />Sampel/<br />Kontrol<br />Inkubasi<br />Suhukamar<br />60’<br />Campur rata<br />20-30 ‘’<br />Microwells<br />100 µL<br />Thyroxineenzime conjugate <br />Campur rata 30 ‘’<br />100 µL<br />Working Substrate solution<br />Reagen A&B<br />1:1<br />Buang<br />Cuci-bilas<br />5 x<br />Hilangkansisa air dg absorbent paper<br />50 µL<br />Stop solution<br />Inkubasi<br />Suhukamar<br />20’<br />Baca OD <br />450 nm, 30’<br />
  47. 47. TUTOR IMUNOLOGI<br />1<br />2<br />3<br />4<br />fT4 dapatmemberikanpenilaian yang lebihakuratuntukpenilaian status tiroiddaripada<br />T4 total<br />Perubahan serum binding protein -> perubahan T4 total, namunkadar fT4 tetaptidakberubah<br />fT4 ↑ : <br />hipertiroidisme<br />fT4 ↓ :<br />hipotiroidisme.<br />Range fT4 normal :<br />0,8 - 2,0 ng/dL<br />34<br />
  48. 48. Thank You !<br />www.themegallery.com<br />
  49. 49. NORMAL VALUE<br />TUTOR IMUNOLOGI<br />
  50. 50. TUTOR IMUNOLOGI<br />
  51. 51. Kurvastandar TSH<br />TUTOR IMUNOLOGI<br />absorbans<br />Konsentrasi TSH µIU/mL<br />
  52. 52. Obat yang mempengaruhitiroid<br />Dopamine : mengurangisekresi TSH<br />Glukokortikoid : mengurangisekresi TSH<br />Lithium : menurunkan fT4<br />Yodida : menurunkan fT4<br />Amiodaron : meningkatkanataumenekan fT4<br />Estrogen : mempengaruhi TBG<br />Androgen : mempengaruhi TBG<br />TUTOR IMUNOLOGI<br />
  53. 53. Pemantauanterapi<br />TUTOR IMUNOLOGI<br />Perubahan TSH serum lambat, butuhwaktubeberapabulanuntukkembalikerentang normal<br />Pengukuran T4 serum lebihbaikdaripada TSH sebagaiujitunggalfungsitiroidbilakondisi steady state belumtercapai, misalnyapadafaseawalpengobatantirotoksikosis<br />
  54. 54. interferensi<br />Reaksisilang<br />Antibodianalit endogen<br />Antibodiheterofilik<br />Interaksiobat<br /> Heparin merangsang lipoprotein lipase melepaskanasamlemakbebas yang menghambatikatan T4 pada protein serum<br />Furosemide<br /> Uremia<br />TUTOR IMUNOLOGI<br />
  55. 55. TSH <br />Anaklahir 4 hari 1.0-39.0 mIU/L<br />2-20 minggu 1.7-9.1<br />21 minggu-20th 0.7-64.0 <br />Dewasa 21-54th 0.4-4.2 <br />55-87 tahun 0.5-8.9<br />Kehamilan trimester 1 0.3-5.2<br />TUTOR IMUNOLOGI<br />
  56. 56. T4 <br />Neonatus > 6.5 ug/dL<br />Dewasa 4.6-11.0<br />T3 <br />Dewasa 20-50 tahun 70-204 ng/dL<br /> 50-90 tahun 40-181<br />T3 Dewasa 10-28 ng/dL<br />FT4 Dewasa 0.8-2.0 ng/dL<br />TUTOR IMUNOLOGI<br />
  57. 57. Thyroxine<br />TUTOR IMUNOLOGI<br /><ul><li>= 3,5,3',5'-tetraiodothyronine (T4) : major thyroid hormones secreted by the follicular cells of the thyroid gland
  58. 58. synthesized via the iodination and covalent bonding of the phenyl portions of tyrosine residues found in an initial peptide, thyroglobulin, which is secreted into thyroid granules.
  59. 59. These iodinated diphenyl compounds are cleaved from their peptide backbone upon being stimulated by thyroid-stimulating hormone.</li></li></ul><li>T4 is transported in blood, with 99.95% being protein-bound, principally to thyroxine-binding globulin (TBG), and, to a lesser extent, to transthyretin and serum albumin.<br />The half-life of thyroxine once released into the blood circulatory system is about 1 week.<br />TUTOR IMUNOLOGI<br />
  60. 60. Efek T4<br />controlling the rate of metabolic processes in the body and influencing physical development, increase the concentration of nerve growth factor in the brains.<br />Thyroxine is a prohormone and a reservoir for the active thyroid hormone triiodothyronine (T3), which is about four times more potent. <br />T4 is converted in the tissues by deiodinases, including thyroid hormone iodine peroxidase (TPO), to T3. The "D" isomer is called "Dextrothyroxine" and is used as a lipid modifying agent.<br />TUTOR IMUNOLOGI<br />
  61. 61. Thyroxine can be measured as free thyroxine, which is an indicator of thyroxine activity in the body. It can also be measured as total thyroxine, which also depends on the thyroxine that is bound to thyroxine-binding globulin. <br />A related parameter is the free thyroxine index, which is total thyroxine multiplied by thyroid hormone uptake, which, in turn, is a measure of the unbound thyroxine binding globulins.<br />The normal human adult range of T4 in blood is 4 - 11 mcg/dL<br />TUTOR IMUNOLOGI<br />
  62. 62. TUTOR IMUNOLOGI<br />
  63. 63. TUTOR IMUNOLOGI<br />
  64. 64. TUTOR IMUNOLOGI<br />
  65. 65. Triiodothyronine<br />effects of T3 on target tissues are roughly four times more potent than those of T4. <br />Of the thyroid hormone that is produced, just about 20% is T3, whereas 80% is produced as T4. <br />Roughly 85% of the circulating T3 is later formed in the thyroid by removal of the iodine atom from the carbon atom number five of the outer ring of T4. In any case, the concentration of T3 in the human blood plasma is about one-fortieth of that of T4. This is observed in fact because of the short half-life of T3, which is only 2.5 days. This compares with the half-life of T4, which is about 6.5 days.<br />TUTOR IMUNOLOGI<br />
  66. 66. T3 and T4 are carried in the blood - bound to plasma proteins<br />There are three main proteins that the two hormones are bound to<br />Thyronine-binding globulin (TBG) is a glycoprotein that has a higher affinity for T4 than for T3<br />Transthyretin is also a glycoprotein, but with a higher affinity for T3 than for T4. <br />Albumin, low affinity, but, due to the large availability of albumin, it has a high capacity.<br />TUTOR IMUNOLOGI<br />
  67. 67. Thyroidal Radioiodine Uptake<br />This test does not reflect the patient's thyroid status, but determines the turnover of iodine in the gland. It measures 6 or 24 hours uptake of 131I or 123I after the oral administration of the iodine. Its main use is in the differential diagnosis of the etiology of hyperthyroidism (Table 7). It should be used only when the cause of hyperthyroidism is in doubt, such as in patients with hyperthyroid symptoms, small goiters and no evidence of exophthalmopathy. It is also indicated in the hyperthyroid phase in postpartum thyroiditis to differentiate Graves' disease from destructive thyroiditis.<br />TUTOR IMUNOLOGI<br />
  68. 68. Company name<br />www.themegallery.com<br />TBG and the thyroxine binding site. (a) Structure of TBG with thyroxine (space-filled). The upper half of the Aβ-sheet (blue) is opened, with initial insertion of the reactive loop (red) to P14 threonine, 14 residues before the reactive center P1. (b) Binding pocket showing thyroxine in stick form enclosed between strands 3–5 of the B-sheet and helices H and A and with iodine atoms, contoured at 5 times rms density in a log-likelihood gradient map for anomalous scattering<br />
  69. 69. Company name<br />www.themegallery.com<br />Binding and triggered release of thyroxine. (a) Interactions with adjacent side chains anchor thyroxine within the pocket. Thyroxine release will be triggered on full insertion of P14 threonine (space-filled upper left) displacing Tyr-241 and disrupting the H-bonds that anchor thyroxine and the flanking peptide loop between s4B and s5B (blue). This network will be similarly disrupted by the common presence (19) in Australian aborigines of a Thr at 191 (circled red; see also Fig. 4). (b) The triggered movement of the flanking s4B–5B loop is shown in the homologous pocket in antichymotrypsin. The open pocket of TBG before loop insertion (blue) matches that of active antichymotrypsin (gray). Transition to the fully inserted loop (cyan) or to the partially inserted δ-form (green) in antichymotrypsin both result in a 4- to 5-Å shift of the loop with a contraction of the binding pocket. <br />
  70. 70. TMB <br />TMB (3,3′,5,5′-tetramethylbenzidine) is a chromogen that yields a blue color when oxidized, typically as a result of oxygen radicals produced by the hydrolysis of hydrogen peroxide by HRP. For kinetic or non-stopped ELISA assays, the TMB chromogen has maximal absorbances at 370nm and 652nm. The color then changes to yellow with the addition of sulfuric or phosphoric acid with maximum absorbance at 450nm. A green reaction product may result from partial conversion to the yellow product from the blue intermediate. TMB is very sensitive ELISA substrate and is more quickly oxidized than other HRP substrates, resulting in faster color development.<br />
  71. 71. Free thyroxine index<br />the amount of unbound, physiologically active thyroxine (T4) in serum. This amount is determined by direct assay or, more frequently, calculated on the basis of an in vitro uptake test. In this test the uptake (by resin or charcoal) of labeled triiodothyronine (T3) is measured; because T3 is less strongly bound by serum, it is used instead of T4. The free T4 index is then obtained by multiplying the T3 uptake by the total concentration of T4 in serum. <br />www.themegallery.com<br />Company name<br />
  72. 72. FT4I, T7 assay, T12 assay Endocrinology A lab value for T3 uptake combined with total T4; FTI is a clinical parameter measured by RIA, used to evaluate thyroid function, calculated by T4 x %T3RU–resin uptake; the FTI is ↑ in hyperthyroidism and factitious hyperthyroidism and ↓ in hypothyroidism; it is falsely ↑ in heparin therapy and falsely ↓ in phenytoin and valproic acid therapy, and in the euthyroid sick syndrome<br />TUTOR IMUNOLOGI<br />
  73. 73. TUTOR IMUNOLOGI<br />

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