%7UERMHYL

06WRMNRYL

MEDIKAMENTNA TERAPIJA HIPERTIROIDIZMA

6DHWDN

Hipertiroidizam se definLH

NDR KLSHUPHWDEROLNR VWDQMH ]ERJ KLSHUIXQNFLMH

WLURLGQRJ WNLYD 8]URFL KLSHUWLURLGL]PD VX GLIX]QD WRNVLQD VWUXPD XQLQRGR]QD LOL SROLQRGR]QD WRNVLQD VWUXPD WXPRU KLSRIL]H NROL OXL WLURWURSLQ 76+ KLSHUVHNUHFLMD

humanog horionskog gonadotropina (h&* L KLSHUIXQNFLMD HNWRSLQRJ WLURLGQRJ WNLYD

'LMDJQR]D KLSHUWLURLGL]PD VH SRVWDYOMD QD RVQRYX NOLQLNRJ QDOD]D L SRWYUXMH VH ODERUDWRULMVNLP SRGDFLPD R VQLHQRP WLURWURSLQX RGUHLYDQMH VORERGQH IUDNFLMH WLURLGQLK

hormona (FT4 ili FT3) se koristi u praHQMXHIHNDWDWHUDSLMHKLSHUWLURLGL]PD

8 OHHQMX KLSHUWLURLGL]PD QD UDVSRODJDQMX VX PHGLNDPHQWQD WHUDSLMD WLRQDPLGLPD WHUDSLMVND GR]D UDGLRMRGDLOLOHHQMHKLUXUNLP SXWHP 7LRQDPLGL VX XXSRWUHELYLHRG HVW

decenija; njihova efikasnost je nesporna aliMHXSRWUHEDRJUDQLHQDYUVWRPKLSHUWLURLGL]PDL

PRJXLP QHHOMHQLP GHMVWYLPD OHNRYD 8 QDRM ]HPOML VX QD UDVSRODJDQMX GYD OHND L] RYH

grupe, metimazol (MMI) i propiltiouracil (PTU). Indikacije za primeni tionamida su primarni tretman autoimunskog hipertiURLGL]PD GLIX]QD WRNVLQD VWUXPD L SULSUHPD ]D
GHILQLWLYQR OHHQMH KLSHUWLURLGL]PD X QRGR]QRM WRNVLQRM VWUXPL 3R]QDWL VX PQRJREURMQL QHHOMHQL HIHNWL RYLK OHNRYD DOL VX DJUDQXORFLWR]D WRNVLQL KHSDWLWLV L YDVNXOLWLV RSDVQH

posledice zbog kojih se upotreba ovih lekova prekida. Tionamidi se mogu dati i efikasni su
X NRQWUROL KLSHUWLURLGL]PD WUXGQLFD GRMLOMD GHFH L RPODGLQH 8SUNRV UD]OLLWLP YLGRYLPD SULPHQH SRVWL]DQMH RSRUDYND UHPLVLMH KLSHUWLURLGL]PD SRG GHMVWYRP WLRQDPLGD PRH VH RHNLYDWLXGROHHQLK

Abstract: Hyperthyroidism is defined as hypermetabolic state as a consequence of hyperfunctioning thyroid tissue. The causes of hyperthyroidism are diffuse toxic goitre, uninodular or multinodular hyperfunctioning goitre, pituitary tumour secreting thyrotropin (TSH), hypersecretion of human chorionic gonadotropine and hyperfunctionig ectopic thyroid tissue. The diagnosis of hyperthyroidism makes on clinical grounds and confirms by low or unmesurable level of thyrotropin. The determination of free thyroid hormones (FT3 or FT4) is better in follows of therapeutic effects. For the treatment of hyperthyroidism we have three general principles- medicaments (thionamides), surgery or radioactive iodine. The thionamides, methimazole (MMI) and propylthiouracil (PTU) are in use more than sixty years. These drugs are verry effective but they have a lot of undesirable effects. Among the most serious side effects of thionamides are agranulocytosis, toxic hepatitis and vasculitis. Less dangerous consequences of thionamide drugs are skin rush, poliartrhralgias, pruritus and gastrointestinal incompliance. These drugs are also effective and safe in pregnant and lactating women as wwll as in children and adolescents. Instead of different therapeutic protocols these drugs are effective in only about 50% of treated patients.

* 'U %RR 7UERMHYL, profesor interne medicine, Medicinski fakultet Beograd, e-mail:btrbojev@eunet.yu
+LSHUWLURLGL]DPVHGHILQLHNDRKLSHUPHWDEROLNRVWDQMH]ERJGHORYDQMDYLNDWLURLGQLKKRU mona poreklom iz tiroidnog tkiva. Ovaj entitet se razlikuje i nije sinonim sa tirotoksikozom, stanjem koje je SRVOHGLFD WRNVLQRJ HIHNWD YLND WLURLGQLK KRUPRQD EH] RE]LUD QD QMLKRYR SRUHNOR HQGRJHQL LOL HJ]RJHQL L]YRUL 8]URFL KLSHUWLURLGL]PD VX UD]OLL WDEHOD  DOL MH QDMHL X]URN KLSHUWLURLGL]PD X WL VYLP JHRJUDIVNLP REODVWLPD WRNVLQD GLIX]QD VWUXPD DXWRLPXQVNL KLSHUWLURLGL]DP *UDYHV RYD LOL %DVHGRZOMHYDEROHVW2FHQMXMHVHGDMHRSWDXHVWDORVWVYLKREOLNDKLSHUWLURLGL]PDXVYHWXRNRX HQ

skoj i oko 0.2% u mukoj populaciji. (1)

Tabela 1. Uzroci hipertiroidizma

Naziv 1. 'XIX]QD WRNVLQDVWUXPD*UDYHVR YDLOL . Basedow ljeva bolest) 2. 8Q LQ RGR]Q DWRNVLQDVWUXPD 3. PoOLQR GR]Q DWRNVLQD VWUXPD 4. Tirotropinom 5. Hipersekrecija humanog horionskog gonadotropina 6. Struma ovarii

Pretpostavljeni mehanizm nastanka hipertiroidizma

$XWRLPLQVNLSRUHPHDMVD VWYDUDQMHPDQWLWHODNRMDVWLP OLX X

TSH receptor i izazivaju hiperfunkciju i rast strume

$ XWRQRPQLQRGXV]E RJSR UHPHDMDNRQ WUROHUDVWD $ XWRQRPQLSRUHPHDM DVWDLOLSRVOHGLFDG HJHQHUDWLYQ LK U

promena u dugotrajnoj strumi Autonomna hipersekrecija TSH iz tumora hipofize

5HWNRX QRU PDOQR M WUXG QRL RE LQRXP ODUQ RMWUX GQRL LOL R

horiokarcinomu
+LSHUIX QNFLMD HNWRSLQR JWLUR LG LQ RJWNLYD

UDGLRDNWLYQL MRG L RSHUDWLYQR OHHQMH 6YD WUL SRVWXSND VX HILNDVQD L XVSHQD DOL VH LS

Na raspolaganju su tri globalna terapijska pristupa hipertiroidizmu- medikamentna terapija, ak stavovi o

SULPHQL RYLK SRVWXSDND ]QDDMQR UD]OLNXMX SRWR QL MHGDQ RG QMLK QH GRYRGL REDYH]QR GR WUDMQRJ HXPHWDEROLQRJVWDQMD

Dijagnoza hipertiroidizma
'LMDJQR]DKLSHUWLURLGL]PDVHSRVWDYOMDQDRVQRYXNOLQLNRJQDOD]DLSRWYUXMHVHODERUDWRULMVNLP SRVWXSFLPD 3UHSRUXHQL SRVWXSDN X GLMDJQR]LKLSHUWLURLGL]PD VKHPDWVNL MHSULND]DQ QDVOLFL 3RVOH NOLQLNRJ QDOD]D SUYL L MHGLQL ODERUDWRULMVNL SRVWXSDN MH RGUHLYDQMH WLLURVWLPXOLXHJ KRUPRQD WLURWURSLQD76+XVHUXPX'DQDQMLSRVWXSFL]DRGUH

ivanje TSH su dovoljno osetljivi, pouzdani i

SUHFL]QL GD QHPD SRWUHEH GD VH RGPDK SUHGX]LPDMX VNXSL SRVWXSFL RGUHLYDQMD RFHQMHQLK VORERGQLK IUDNFLMD()WLURLGQLKKRUPRQD7HNDNRMH76+QL]DNRGUHXMHVHVORERGQDIUDNFLMDWLURNVLQD)7

ili trijodtiroQLQD)7UDGLEROMHJSUDHQMDHIHNWDWHUDSLMH.RQFHQWUDFLMDWLURWURSLQDXVHUXPXVH]ERJ logaritamsko- linearnog odnosa sa tiroidnim hormonima relativno sporo menja tako da nije pogodna za
SUDHQMH WHUDSLMVNLJ HIHNWD $NR MH )7 QRUPDODQ D 76+ QL]DN RGUHXMH VH VORERGQL WULMRGWLURQLQ  )7 X VHUXPX X PQRJLK EROHVQLFD VD *UDYHV RYLP REROMHQMHP HVWD MH SRMDYD GD SUYR UDVWH

trijodtironin a tek potom dolazi i do porasta tiroksina u krvi. Takozvana T3 tirotoksikoza, hipertiroidizam sa povienim trijodWLURQLQRP 7 X] QRUPDODQ LOL EODJRSRYLHQWLURNVLQQLMHHVWD L
SR PRP LVNXVWYX ]QDWQR MH UHD RG SRGDWDND X OLWHUDWXUL JGH VH RFHQMXMH DN GR  VYLK

hipertiroidizama.
7LURWURSLQ X FHQWUDOQRP KLSRWLURLGL]PX PRH ELWL VQLHQ DOL VX WDGD SULVXWQL L NO LQLNL ]QDFL KLSRPHWDEROL]PD L HVWR L GUXJLK VHNXQGDUQLK HQGRNULQRSDWLMD 8NXSQH NRQFHQWUDFLMH WLURLGQLK KRUPRQD X FLUNXODFLML ]DYLVH RG PQRJLK QHWLURLGQLK LQLODFD JGH MH QD SUYRP PHVWX XWLFDM SURPHQH NRQFHQWUDFLMH WUDQVSRUWQLK SURWHLQD 8 WUXGQRL QD

primer, kao i u osoba koje uzimaju oralne

NRQWUDFHSWLYHLOLDNR SRVWRMLXURHQLSRUHPHDMX VLQWH]LWUDQVSRUWQLKSURWHLQDPRJXVHQDLSRYLHQH YUHGQRVWL XNXSQRJ DOL QH L VORERGQRJ WLURNVLQD X SOD]PL 8 RYLP NDR L X UHWNLP VOXDMHYLPD YLVRNLK

vrednosti tiroidnih hormona (ukupnih ili slobodnih) zbog prisustva antitela prema tiroksinu i/ ili
WULMRGWLURQLQXRVREDMHNOLQLNLHXPHWDEROLQDLYUHGQRVWL76+VXQRUPDOQH 1DOD] QRUPDOQLKYUHGQRVWL76+XVHUXPXQHOHHQHRVREHVNRURXYHNLVNOMXXMHKLSHUWLURLGL]DP L]X]HWDN MH WXPRU KLSRIL]H NRML OXL 76+ WLURWURSLQRP $NR SRVWRML RYDM WXPRU PRJX VH QDL QRUPDOQH LOL EODJR SRYLHQH YUHGQRVWL 76+ L SRYLHQH YUHGQRVWL WLURLGQLK KRUPRQD VD NOLQLNLP ]QDFLPD KLSHUWLURLGL]PD1LHYUHGQRVWL 76+QHPRUDMXXYHNGD ]QDH WLURWRNVLNR]X76+ PRHELWL

nizak u tekim, netiroidnim bolestima ili ako osoba uzima lekove kao to su kortikosteroidi ili dopamin kao i u manjeg broja zdravih starijih osoba.(4,5)

/HHQMHKLSHUWLURLGL]PD

3RVWXSFLXOHHQMXKLSHUWLURLGL]PDLWLURWRNVLNR

ze mogu biti usmereni ka smanjenju hipersekrecije

WLURLGQLKKRUPRQDNDX]URNXKLSHUWLURLGL]PDLOLVHRHNXMHXEODDYDQMHLSRYODHQMHNOLQLNLK]QDNRYD KLSHUWLURLGL]PD 1D UDVSRODJDQMX VX WUL RVQRYQD SRVWXSND X OHHQMX KLSHUWLURLGL]PD

- medikamentni, aplikDFLMD UDGLRMRGD L RSHUDWLYQR OHHQMH .RML H RG UDVSRORLYLK SRVWXSDND ELWL SULPHQMHQ ]DYLVL RG

PQRJRLQLODFDQDSUYRPPHVWXRGX]URNDKLSHUWLURLGL]PDGUXJLKSULGUXHQLKEROHVWLLVWDQMDWUDMDQMD PHWDEROLNRJSRUHPHDMDDOLLHOMDEROHVQLFDX]LPDMX

i u obzir i estetske okolnosti.

.RG NRQ]HUYDWLQRJ PHGLNDPHQWQRJ SRVWXSND QD UDVSRODJDQMX MH YLH UD]OLLWLK OHNRYD VD UD]OLLWLP PHKDQL]PRP GHMVWYD =ERJ UD]OLLWLK PHKDQL]DPD GHMVWYD UD]OLNXMX VH L LQGLNDFLMH L RHNLYDQL HIHNWL RYLK OHNRYD WDEHOD 

Medikamentna terapija hipertiroidizma u dananjem smislu

UHL X XSRWUHEL MH YLH RG SROD YHND  JRGLQH -RKQ $VWZRRG MH XYHR X NOLQLNX SUDNVX SUYL WLRQDPLGSURSLOWLRXUDFLOLYHJRGLQHREMDYOMHQLVXSUYLUH]XOWDWLSULPHQHRYRJOHND.DVQLMHVX

razvijeni i drugi preparati iz ove grupe koji su danas u irokoj i uspenoj primeni.

Mehanizam dejstva tionamida

7LRQDPLGL VX UHODWLYQR MHGQRVWDYQH PROHNXOH NRMH VDGUH VXOIKLGULOQX JUXSX L WLRXUHX X KHWHURFLNOLQRM VWUXNWXUL VOLND  3URSLOWLRXUDFLO 

-propil-2-tiouracil ) i metimazol (1-metil-2-

PHUNDSWRLPLGD]ROVHGDQDVLURNRNRULVWHX(YURSLL6MHGLQMHQLP'UDYDPDNDUELPD]ROMHXXSRWUHEL

u Ujedinjenom Kraljevstvu i on se intratiroidno konvertuje u metimazol. Ove supstance se aktivno koncentriu u WLURLGQRM OH]GL QDVXSURW NRQFHQWUDFLRQRP JUDGLMHQWX 1MLKRY SULPDUQL HIHNDW MH
LQKLELFLMD VLQWH]H WLURLGQLK KRUPRQD LQWHUIHUHQFLMRP VD WLURLGQRP SHURNVLGD]RP LPH VH VSUHDYD

jodinacija tirozilskih ostataka u tiroglobulinu. Slika 1. Hemijska struktura tionamida

2YL OHNRYL LPDMX L GUXJH ]DSDHQH HIHNWH 3URSLORWLRXUDFLO EORNLUD NRQYHU]LMX WLURNVLQD X WULMRGWLURQLQXSHULIHUQLP WNLYLPDNOLQLNL]QDDMRYRJHIHNWDQLMHYHOLNLMHUVXSRWUHEQHGR]HOHND]D SRVWL]DQMH RYRJ HIHNWD ]QDDMQR YHH RG XRELDM

eno primenjivanih. Tionamidi mogu da imaju primetan imunosupresijski efekat. Nivo antitela prema TSH receptoru (TSHR At) opada u osoba koje
SULPDMX WLRQDPLGH VOLQR VH ]DSDD L ]D GUXJH LPXQVNL ]QDDMQH PROHNXOH LQWUDFHOXODUQX DGKH]LYQX

molekulu 1 i receSWRUH ]D VROXELOQL LQWHUOHXNLQ  L LQWHUOHXNLQ  ,PD GRND]D GD WLRQDPLGL SRGVWLX apoptozu intratiroidnih limfocita i da smanuju ekspresiju molekula II klase sistema tkivne kompatibilnosti (HLA) (6). Dokazano je i smanjenje broja T helper limfocita u cirkulaciji, porast broja
7VXSUHVRUDVPDQMHQMHEURMDSULURGQLK HOLMDXELFDLDNWLYLVDQLK LQWUDWLURLGQLK 7 OLPIRFLWDXRVREDQD

terapiji tionamidima. Uprkos ovim podacima, kod procene eventualnih efekata tionamida na imunski sistem mora se imati na umu i povROMDQXWLFDMXVSRVWYOMDQMDPHWDEROLNHUDYQRWHH
3URSLOWLRXUDFLO L PHWLPD]RO VH EU]R UHVRUEXMX L] GLJHVWLYQRJ WUDNWD L GRVWLX PDNVLPXP

koncentracije u serumu oko 2 sata posle peroralnog unosa. Koncentracija ovih supstanci u serumu nije
SRVHEQR]QDDMQD ]DRVWYDULYDQMHQMLKRYLKHIHNDWDSRWRVHRQLNRQFHQWULXXWLWDVWRMOH]GL3ROXLYRW SURSLOWLRXUDFLODMHNUDLL]ERJWRJDRQPRUDGDVHX]LPDXSRGHOMHQLPGR]DPDGRNVHPHWLPD]ROPRH

X]HWL X MHGQRM GQHYQRM GR]L 3URSLOWLRXUDFLO VH X ]QDDMQRM PHUL YH]

uje sa proteinima plazme dok je

PHWLPD]RO X YHOLNRM PHUL VORERGDQ 'R]H OHND VH QH PHQMDMX ]DYLVQR RG LYRWQRJ GRED EXEUHQH IXQNFLMHLOLIXQNFLMHMHWUHLDNRMHNOLUHQVPHWLPD]RODVPDQMHQNRGRWHHQMDKHSDWLQHIXQNFLMH

.OLQLNDSULPHQDWLRQDPLGD

Dva su osnovna razloga (i uslova) za primenu tionamida: primarni tretman hipertiroidizma ili
SULSUHPD ]D RSHUDWLYQR OHHQMH LOL SULPHQX UDGLRDNWLYQRJ MRGD .DR SULPDUQL WUHWPDQ RQL VH PRJX NRULVWLWL VDPR X OHHQMX DXWRLPXQVNRJ *UDYHV RYRJ KLSHUWLURLGL]PD JGH MH PRJXH RHNLYDWL 

postizanje remisije hipertiroidizma. U svim drugim oblicima hipertiroidizma tionamidi mogu imati
VDPRSULYUHPHQXSULPHQXXSULSUHPL]DGHILQLWLYQXIRUPXWHUDSLMH$QWLWLURLGQLOHNRYLVXSUHSRUXHQL

primarni tretman Graves ove bolesti u trudnica, dece i adolescenata. Odluka o primenio antitiroidnih
OHNRYD ]DYLVL L RG GUXJLK RNROQRVWL NDR WR VX SULGUXHQD VWDQMD NRMD NRPSOLNLMX LOL RQHPRJXDYDMX GUXJH YLGRYH WHUDSLMH -HGQD RG RYLK RNROQRVWL MH L SULVXVWYR WHNH RIWDOPRSDWLMH NRMD PRH G

a se

pogora kod primene radioaktivnog joda.

Izbor leka
.RML H RG UDVSRORLYLK WLRQDPLGD ELWL XSRWUHEOMHQ X YHOLNRM PHUL MH VWYDU OLQRJ L]ERUD

Metimazol koji se daje u jednoj dnevnoj dozi ima prednost jer ga pacijenti radije prihvataju; kod primene meWLPD]ROD GROD]L GR EUH QRUPDOL]DFLMH YUHGQRVWL WLURNVLQD L WULMRGWLURQLQD X VHUXPX 
3URSLOWLRXUDFLO VH QHWR HH NRULVWL X WUXGQLFD L GRMLOMD MHU QHNL UDGRYL GRND]XMX PDQML SUHOD]DN

propiltiouracila kroz placentu i u mleko.

3UDNWLQHRNROQRVWL

UobLDMHQH SRHWQH GR]H PHWLPD]ROD VX  GR  PJ X MHGQRM GR]L GQHYQR SRHWQH GR]H propiltiouracila su 200 do 400 mg, vrlo retko 600 mg dnevno, u podeljenim dozama. Bolest se u YHLQH SDFLMHQDWD PRH NRQWUROLVDWL PDQMLP GR]DPDGDWRJUDVSRQD 8MHGQRMNRQWUR lisanoj studiji, 85 % bolesnika normalizovalo je vrednosti T3 i T4 u serumu posle est nedelja primene samo 10 mg metimazola dnevno. Kada se primenjuje doza od 20 mg metimazola dnevno, ovaj procenat raste samo do 92% (8). Jatrogeni hipotiroidizam je mnogo HLDNRVHSULPHQMXMXYHHGR]HWLRQDPLGD
.DGD VH SRQH VD SULPHQRP WLRQDPLGD WLURLGQD IXQNFLMD VH NRQWUROLH VYDNLK  GR  QHGHOMD VYH GRNVHQHSRVWLJQHVWDELOQDQRUPDOQDYUHGQRVWWLURNVLQDXNUYL8RELDMHQRVHHXWLURNVLQHPLMDSRVWLH

za 8 do 12 nedelja kada se doza tionamida smanjuje i kontrole nastavljaju svaka 3 meseca. Doza
RGUDYDQMD PHWLPD]ROD MH RELQR  PJ GQHYQR UHWNR MH GRYROMQR  J GQHYQR ]D SRWSXQX NRQWUROX EROHVWL 'R]D RGUDYDQMDSURSLOWLRXUDFLOD MHGR PJGQHYQRQDMPDQMHX  GR]H /HHQMHWUDMH QDMPDQMH  RELQR  PHVHFL $NR VH GR]D QH SULODJRGL UD]YLMD VH KLSRWLURLGL]DP VD SRYHDQMHP VWUXPH 7LURWURSLQ X VHUXPX PRH RVWDWL GXJR VXSULPRYDQ DOL VH RELQR QRUPDOL]XMH SRVOH WUL PHVHFD RG SRHWND OHHQMD 7UDMQR QLVNH YUHGQ

osti TSH u serumu su nepovoljan prognozni znak i

XND]XMX QD PDQMX YHURYDWQRX LPXQVNH UHPLVLMH $NR MH 76+ WUDMQR QL]DN XSUNRV QRUPDOQRP

slobodnom tiroksinu u serumu, opravdano je proveriti slobodni trijodtironin jer nekada nedovoljna supresija T3 ukazuje GDMHSRWUHEQRSRYHDWLGR]XWLRQDPLGD

Remisija
5HPLVLMD X PHGLNDPHQWQRM WHUDSLML KLSHUWLURLGL]PD PRH ELWL HQGRNULQD L LPXQVND (QGRNULQD UHPLVLMD QDVWDMH NDGD VH QRUPDOL]XMX YUHGQRVWL WLURNVLQD L WULMRGWLURQLQD X VHUXPX 8RELDMHQR VH RYR SRVWLH]DGRPHVHFDRGSRHWNDWHUDSLMH'RVDGDQLMH]DEHOHHQDUH]LVWHQFLMDQDWLRQDPLGHLDNR QHPDNRPSOLNDFLMDNRMH]DKWHYDMXLVNOMXHQMHOHNDHQGRNULQDUHPLVLMDHREDYH]QRQDVWXSLWL,PXQVND UHPLVLMDVHSRVWLHXQDMYLHGROHHQLKLWRSRVOHQDMPDQMHJ

odinu dana primene lekova. Da bi se govorilo o remisiji pacijent mora biti najmanje 6 meseci bez terapije i bez ponovne pojave

KLSHUPHWDEROL]PD $NR VH SRJRUDQMH PHWDEROLNRJ VWDWXVD MDYL SUH LVWHND RG  PHVHFL X VWYDUL

remisija nije ni postignuta i radi se o egzacerbaciji osnovne epizode bolesti. Kvalitetna remisija
SRGUD]XPHYDSRWSXQRRGVXVWYRNOLQLNLKLODERUDWRULMVNLKSURPHQDWLURLGQHIXQNFLMHEH]WHUDSLMHNRMH WUDMH QDMPDQMH GYH JRGLQH 0RH VH UHL GD SRNXDML SUHGYLDQMD QDVWXSDQMD L NYDOLWHWD UH

misije traju

RG XYRHQMD RYLK OHNRYD X NOLQLNX SULPHQX L GR VDGD QLVX GDOL RHNLYDQ L SRX]GDQ RGJRYRU 3UHGYLDQMH YHURYDWQRH NYDOLWHWQH UHPLVLMH RSUDYGDQR MH GD EL VH L]EHJOD GXJRWUDMQD SULPHQD SRWHQFLMDOQR RSDVQLK SUHSDUDWD  3RUHG WRJD XLQMHQL V

u pokuaji da se razviju bolje strategije

OHHQMD PHX NRMLPD VX SULPHQD DOWHUQDWLYQLK GR]D WLRQDPLGD SURGXHQMH SHULRGD OHHQMD LOL NRPELQDFLMD YHLK GR]D WLRQDPLGLD VD WLURNVLQRP 

block an replace terapija) ali do sada bez vidnih poboljanja stope remisije. Mnoge retrospektivne studije su pokazale da pacijenti sa velikom strumom, tekim hipermetabolizmom, relativno visokim odnosom trijodtironina prema tiroksinu, dugotrajno
VXSULPRYDQLP 76+ NRML VH QH QRUPDOL]XMH VYH GR NUDMD SHULRGD OHHQMD LPDMX PDOX YURYDWQRX H QDVWXSDQMDUHPLVLMH'DQDVMHUDVSURVWUDQMHQDPRJXQRVWRGUHLYDQMDDQWLWHODSUHPD76+UHFHSWRULPD 76+5 $W RPRJXLOD QHWR EROMX PRJXQRVW SUHGYLDQMD UHPLVLMH QD NUDMX WHUDSLMVNRJ FLNOXVD 1DLPH LDNR YLVRN WLWDU 76+5 $W QD SRHWNX SHULRGD OH HQMD QLMH X GREURM NRUHODFLML VD LVKRGRP OHHQMD DNR VH QH SULPHWL ]QDDMDQ SDG WLWUD RYLK DQWLWHOD QD NUDMX WHUDSLMVNRJ FLNOXVD PRH VH RHNLYDWLGDHXEU]RQDVWXSLWLSRJRUDQMHPHWDEROLNHNRQWUROH6XSURWQRSDGWLWUD76+5$WQH]QDL GDHVHSRVWL

i kvalitetna remisija.

$NR WLRQDPLGL LPDMX LPXQRVXSUHVLYQR GHMVWYR PRJOR EL VH RHNLYDWL GD GD H YHH GR]H L GXL SHULRG OHHQMD SRYHDWL YHURYDWQRX QDVWXSDQMD L GXLQH WUDMDQMD UHPLVLMH ,DNR VX QHNH VWXGLMH SRND]DOHGDSHULRGOHHQMDRGPHVHFLSRYH DYDYHURYDWQRXUHPLVLMHXRGQRVXQDSHULRGOHHQMDRG  PHVHFL GDOMD SUDHQMD GR HWLUL JRGLQH L YLH SR SUHNLGX WHUDSLMH QLVX SRND]DOD GD OHHQMH GXH RG

godinu dana ima bilo kakav povoljan efekat na stopu i kvalitet remisije (11). Zbog toga se danas SUHSRUXXMH GD WHUDSLMVNL FLNOXV WUDMH  GR  PHVHFL 1HNL SDFLMHQWL
JRGLQDPD L GHFHQLMDPD X]LPDMX PDOH GR]H WLRQDPLGD L RGUDYDMX VWDELOQR PHWDEROLNR VWDQMH

pokuaji prekidanja ovih malih doza posle vie od 10 godina uzimanja doveli su do pogoranja
PHWDEROLNHNRQWUROH3RWRQHPDQLMHGQRJWHRULMVNRJUD]ORJDGDVHRYDNRPDOHGR]HWLRQDPLGDGR PJ PHWLPD]ROD RGQRVQR  PJ SURSLOWLRXUDFLOD GQHYQR QH SULPHQMXMX X RGDEUDQLP VOXDMHYLPD OHHQMHPDOLPGR]DPDWLRQDPLGDPRHELWLWUDMQR .RQDQR XLQMHQL VX SRNXDML GD VH VWRSD UHPLVLMH SRYHD SULPHQRP UHODWLYQR YHLK GR]D

tionamida uz nadoknadu tiroksina. Iako je prvobitno navedeno da se ovim block and replace SRVWXSNRP VWRSD UHPLVLMH GLH QD SUHNR  NDVQLML UDGRYL QLVX SRWYUGLOL RYDNR SRYRO jan efekat. Zbog toga je block and replace postupak danas rezervisan samo za ekstremno nestabilne forme
KLSHUWLURLGL]PDJGHNRGPDOHSURPHQHGR]HWLRQDPLGDGROD]LGRL]UD]LWLKPHWDEROLNLKSRVOHGLFD

3UHNLGOHHQMD

'HFDLDGROHVFHQWLVHRELQROHH XHRGRGUDVOHSRSXODFLMHQDMHHGXHRGJRGLQH2GUDVOH G RVREHX]LPDMXWLRQDPLGHQDMPDQMHDQDMGXHPHVHFLLSRWRPVHWHUDSLMDSUHNLGD$NRMHSULPHQD WLRQDPLGD SUHNLQXWD SRVOH SDU QHGHOMD LOL PHVHFL OHHQMD EH] SRJRUDQMD PHWDEROLNH NRQWUROH RLJOHGQR MH GD QLMH UH R DXWRLPXQVNRP *UDYHV RYRP KLSHUWLURLGL]PX 8 WLP VOXDMHYLPD VH RELQR UDGLRSUROD]QRMWLURWRNVLQRMID]LWLURLGLWLVDNDGDWLRQDPLGHQLMHQLWUHEDORXYRGLWL8RELDMHQRMHGR]D

tionamida kod prekidanja svedena na 10 mg metimazola odnosno 100 mg propiltiouracila dnevno.

1HPDNRQWUROLVDQLKVWXGLMDNRMHVXGRND]DOHGDSRVWHSHQRVPDQMHQMHGR]HWLRQDPLGDXGXHPSHULRGX YUHPHQDVPDQMXMHYHURYDWQRXUHFLGLYD=ERJWRJDQLMHRSUDYGDQRGDVHGR]HGXJRWUDMQRLSRVWHSHQR

smanjuju (na primHU  PJ PHWLPD]ROD QD GUXJL GDQ L VO MHU VH WLPH QHSRWUHEQR SRYHDYDMX WURNRYL
OHHQMD 9HURYDWQRD UHFLGLYD MH YHD DNR RVRED NRG LVNOMXHQMD WHUDSLMH LPD QRUPDOQH YUHGQRVWL WLURLGLQLKKRUPRQD DOLLGDOMHVXSULPRYDQ76+5HFLGLYLQDVWXSDMXRELQRGR

2 meseci po prekidu

WHUDSLMH LVSRG  PHVHFL UDGL VH R HJ]DFHUEDFLML 3RVOH JRGLQX GDQD VWRSD UHFLGLYD RSDGD L ]DGUDYD SODWR XQDUHGQLK MHGQXGRGYH JRGLQHXNXSQD VWRSD UHFLGLYDSRVOHGYHJRGLQHMHRELQRGR 2NR   HQD NRMH SRVWLJQX UHPLVLMX DNR RVWDQX JUDYLGQHLVSROMHUHFLGLYXSRVOHSRURDMQRPGREX  NRMLWUHEDUD]OLNRYDWLRGWLURWRNVLQHID]HSRVOHSRURDMQRJWLURLGLWLVD.RQWUROHSDFLMHQDWDXUHPLVLMLVX GRLYRWQHSRWRMHUHFLGLYPRJXLYLHGHFHQLMDSRVOHLQLFLMDOQHHSL]RGHEROHVWL

1H

eljeni efekti tionamida

7LRQDPLGL PHWLPD]RO NDUELPD]ROL SURSLOWLRXUDFLOLPDMXYHOLNLEURMUHODWLYQREODJLKQHHOMHQLK

HIHNDWD DOL LPDOLEURMRSDVQLKDNLIDWDOQLKSRVOHGLFD1HHOMHQLHIHNWLPHWLPD]RODVXGR]QR]DYLVLQL

dok kod primene propiltiouracila dozna zavisnost nije tako jasna. Blagi, minor uzgredni efekti koji
QDMHH SUHGVWDYOMDMX NRQH UHDNFLMH XUWLNDULMD L PDNXOR]QD RVSD DUWUDOJLMH L JDVWURLQWHVWLQDOQH

nelagodnosti javljaju se u do 5% pacijenata bez obzira koji je preparat u pitanju (metimazol ili
SURSLOWLRXUDFLMO %ODJH NRQH UHDNFLMH VH SRYODH NRG SULPHQH DQWLKLVWDPLQLND L WHUDSLMD VH QDVWDYOMD $OWHUQDWLYQRPRHVHMHGDQWLRQDPLG]DPHQLWLGUXJLPDOLMHXNUWHQDUHDNWLYQRVWSUHNR7HUDSLMD VH PRH WUDMQR SUHNLQXWL L SDFLMHQW P RH ELWL XSXHQ QD GHILQLWLYQR OHHQMH RSHUDFLMRP DNR MH SRVWLJQXWHXPHWDEROL]DPRGQRVQRUDGLRMRGRP$UWUDOJLMHLDNRR]QDHQHNDRPLQRUSRVOHGLFHPRJX ELWLWDNRX]QHPLUDYDMXHGDVHWLRQDPLGLLVNOMXXMXLEROHVQLNXSXXMHQDGUXJHYLGRYHOHHQMD .RG RGOXNH R SUHNLGX OHHQMD PRUD VH ELWL RSUH]DQ MHU EL SRQRYQR XYRHQMH WLRQDPLGD ELOR SRYH]DQRVDYHLPUL]LNRPRGWHLKIRUPLQHHOMHQLKSRVOHGLFDOHNRYD

Agranulocitoza izaziva najvie strahovanja kod terapije tionamidima. Prema nalazima u velikim studijama, agranulocitoza, apsolutni broj granulocita ispod 500 u kubnom milimetru krvi, nalazi se u
SURPLODOHHQLKSURSLOWLRXUDFLORPLXSURPLODOHHQLKPHWLPD]RORP$JUDQXORFLWR]DPRUDGDVH UD]OLNXMHRGSUROD]QHJUDQXORFLWRSHQLMHNRMDMHHVWDX

Graves ovoj bolesti (granulociti i do ispod 1500

X NXEQRP PLOLPHWUX SUH SRHWND WHUDSLMH L QDURLWR SR XYRHQMX WLRQDPLGD =ERJ WRJD MH SUH XYRHQMDWLRQDPLGDNRULVQRX]HWLED]DOQHYUHGQRVWLOHXNRFLWDXNUYL 1DMHHVHDJUDQXORFLWR]DLVSROMLXSUYDULPHVHFDRGSRHWNDWHUDSLMHDOLMHPRJXDLSRVOHYLH W RG JRGLQX GDQD OHHQMD 2SDVQRVW RG DJUDQXORFLWR]H MH YHD X VWDULMLK RVRED L PRJXQRVW IDWDOQRJ LVKRGD X RYRM SRSXODFLML MH YHD $JUDQXORFLWR]D PRH GD VH MDYL NRG SRQRYQH SULPHQH X OHHQMX

recidiva i ako je u prethodnoj epizodi primena istog preparata prola bez posledica. Agranulocitoza je posledica imunskih mehanizama; dokazano je postojanje antigranulocitnih DQWLWHODVDFLWRWRNVLQLPHIHNWRPQDJUDQXORFLWH$QWLQHXWURILOQDFLWRSOD]PDWVNDDXWRD titela (ANCAc) n
PRJX GD LPDMX XORJX X QDVWDQNX DJUDQXORFLWR]H SRWR MH QDHQR GD VH FLOMQL DQWLJHQL QD SULPHU SURWHLQD]DPRHLVSROMLWLQDSRYULQLQHXWURILOD5XWLQVNRSUDHQMHEURMDOHXNMRFLWDQLMHRGSRPRL

poto gubitak leukocita nastaje iznenada.=ERJWRJDVYDNLSDFLMHQWNRGXYRHQMDWHUDSLMHWLRQDPLGLPD

NDRLQDNRQWURODPDWUHEDGDEXGHLQVWULUDQGDVHXVOXDMXSRMDYHERODXJUOXNDRNRGJQRMQHDQJLQH LVNRNDWHOHVQHWHPSHUDWXUHRGPDKMDYLXSUYXXVWDQRYXJGHHPXVHL]EURMDWLOHXNRFLWLXN

rvi. Ako je

QMLKRY EURM LVSRG  PP WHUDSLMD WLRQDPLGLPD VH 2'0$+ 35(.,'$ L EROHVQLN VH XSXXMH

endokrinologu (ne hematologu) na dalji tretman. Ako je broj granulocita preko 1000 / mm3 ali ispod  PP VDYHWXMH VH SDOMLYR SUDHQMH VD HVWLP VYDNR dnevnim) kontrolama broja granulocita u krvi.
7HPSHUDWXUDLEROXJUOXVXQDMHL]QDFLDJUDQXORFLWR]HDOLMHLVHSVDPRJXDNDGDVHLVSROMDYD

naglim skokom temperature sa groznicom i prostracijom. Terapija agranulociteze podrazumeva izolaciju i primenu antibiotika peroralno ili parenteralno zavisno od procenjene ozbiljnosti. Primena faktora koji stimulie granulocitopoezu (G-&6)PRHGDVNUDWL SULRG RSRUDYNDDOLFHQDSUHSDUDWD QH opravdava rutinsku primenu. Ako je oporavak usporen, potrebno je pregledati DVSLUDW NRWDQH VUL depresija mijeloidnih prethodnika opravdava primenu G-CSF (15). Ukrtena reakcija metimazola i propiltiouracila u nastanku agtranulocitoze je odavno dokazana i zamena jednog preparata drugim u VOXDMXSRMDYHRYHNRPSOLNDFLMHQLMHGR] voljena.
+HSDWRWRNVLQRVW MH GUXJD WHND QHHOMHQD SRVOHGLFD WLRQDPLGD 2FHQMHQD XHVWDORVW RYH NRPSOLNDFLMH MH RG GR  SURFHQWD 3UHSR]QDYDQMH KHSDWRWRNVLQRVWL L]D]YDQH SURSLOWLRXUDFLORP PRH ELWL WHNR SRWR GR  RVRED VD QRUPDOQLP WHVWRYLPD MHW

re ispoljava porast transaminaza po

XYRHQMX SURSLOWLRXUDFLOD 3RUDVW WUDQVDPLQD]D MH RELQR SUROD]DQ L QH SUHOD]L GYRVWUXNX YUHGQRVW RG JRUQMH JUDQLFH GR]YROMHQRJ UDVSRQD $VLPSWRPVNL SRUDVW WUDQVDPLQD]D L QDURLWR DONDOQH IRVIDWD]H PRH GD VH YLGL X KL SHUWLURLGL]PX L SUH SRHWND OHHQMD WLRQDPLGLPD EH] GDOMHJ SRJRUDQMD NDGD VH

uvedu tionamidi.
3URVHQR WUDMDQMH WHUDSLMH SURSLOWLRXUDFLORP SUH SRMDYH KHSDWRWRNVLQRVWL MH RNR  PHVHFD +HSDWRWRNVLQRVWL]D]YDQDSURSLOWLRXUDFLORPLPDPHKDQL]DPDOHUJLMVNRJ

hepatitisa sa laboratorijskim

QDOD]LPD KHSDWRFHOXODUQRJ RWHHQMD VD VXEPDVLYQRP LOL PDVLYQRP QHNUR]RP KHSDWRFLWD X X]RUNX ELRSVLMH 7HUDSLMD VH VDVWRML X QHRGORQRP SUHNLGX SULPHQH SURSLOWLRXUDFLOD X] SDOMLYR SUDHQMH

testova funkcije jetre i hepatoprotektivne mere. Iako se saoptava da je mortalitet od ove komplikacije

RGGRYHURYDWQRVHEODLVOXDMHYLQLNDGDQHRWNULMXWDNRGDMHXNXSQDVWDWLVWLNDQHSRX]GDQD

Rutinska kontrola funkcijskih testova jetre osoba na terapiji propiltiouracilom nije RG SRPRL ]ERJ
PRJXLKEHQLJQLKSURPHQDNRMHVXYHRSLVDQH 5HGDN KHSDWLQL SRUHPHDM RVRED OHHQLK PHWLPD]RORP MH WLSLDQ KROHVWD]QL SURFHV 8]RUFL ELRSVLMH SRND]XMX RXYDQX DUKLWHNWXUX OREXOXVD VD LQWUDNDQDOLNXODUQRP KROHVWD]RP L EODJRP

periportnom inIODPDFLMRP3RVOHSUHNLGDOHHQMDSRSUDYLOXQDVWXSDSRWSXQDOLVSRURSRUDYDN3RWRMH
PHKDQL]DPQDVWDQNDKHSDWLQLKSRUHPHDMDNRGSULPHQHPHWLPD]RODRGQRVQRSURSLOWLRXUDFLODUD]OLLW PRJXDMH]DPHQDMHGQRJSUHSDUDWDGUXJLPXVOXDMXSRMDYHKHSDWLQHU

eakcije.

9DVNXOLWLV MH WUHD ]QDDMQD WRNVLQD UHDNFLMD WLRQDPLGD VNRUR LVNOMXLYR SRYH]DQD VD SULPHQRP SURSLOWLRXUDFLOD 8 QHNLK SDFLMHQDWD VD RYRP NRPSOLNDFLMRP PRJX VH QDL SR]LWLYQL VHURORNL WHVWRYL

za lupus (16). Opisan je i vaskulitis sa antitelimaSUHPDFLWRSOD]PLQHXWURILODRSHWHLNRGSULPHQH

SURSLOWLRXUDFLOD9HLQDRYLKRVREDSRUHGSR]LWLYQLKSHULXQXNOHDUQLKDQWLFLWRSOD]PDDQWLWHOD$1&$S LPD SR]LWLYQD L DQWLPLMHORSHURNVLGD]D DQWLWHOD  6PDWUD VH GD SURSLOWLRXUDFLO PRH GD UHDJXMH VD

mLMHORSHURNVLGD]RPLGDVWYDUDPHXSURL]YRGHNRMLSURPRYLXDXWRLPXQVNR]DSDOMHQMH
.OLQLND VOLND DQWLQHXWURILO DQWLWHOR SR]LWLYQRJ YDVNXOLWLVD L]D]YDQRJ WLRQDPLGLPD REXKYDWD

akutnu renalnu disfunkciju, DUWULWLV NRQH XOFHUDFLMH YDVNXOLWLVQX RVSX L respiratorne simptome koji odgovaraju Goodpasteur RYRP VLQGURPX ,DNR VH SURPHQH SR SUDYLOX SRYODH SR SUHNLGX SULPHQH leka, nekada su potrebni kortikosteroidi u velikim dozama i ciklofosfamid a retko i kratkotrajna hemodijaliza (19). Treba znati da neki pacijenti sa Graves ovim oboljenjem imaju pozitivna
DQWLQHXWURILOQD DQWLWHOD L SUH SRHWND WHUDSLMH  1HHOMHQH SRVOHGLFH SULPHQH WLRQDPLGD GDWH VX X

tabeli 2.
$QWLWLURLGQLOHNRYLXWUXGQRLLODNWDFLML*UDYHVRYDEROHVWMHQDMHDXSRSXODFLMLPODGL KHQVNLK RVRED =ERJ WRJD MH PRJXD SRMDYD KLSHUWLURLGL]PD X WUXGQRL L X SHULRGX GRMHQMD RFHQMXMH VH GD VH ELORNRMLREOLNKLSHUWLURLGL]PDMDYOMDXRGGRWUXGQRD3RWRKLSHUWLURLGL]DPSUHGVWDYOMD

opasnost i za majku i za fetus, odmah posle GRND]LYDQMD REROMHQMD VDYHWXMH VH XYRHQMH WHUDSLMH tionamidima (21). Nekada se smatralo da propiltiouracil prolazi placentu u manjoj meri i zbog toga je
SULPHQD RYRJ SUHSDUDWD IDYRUL]RYDQD X WUXGQRL .DVQLMH MH SRND]DQR GD L SURSLOWLRXUDFLO SUROD]L

placentu i danas nema dokaza da bilo koji od tionamida ima prednosti u trudnice ili dojilje (22). Tabela Medikamentna terapija hipertiroidizma
Preparat Tionamidi 1. Metimazol 2. Propiltiouracil 3. Karbimazol Beta adrenergijski antagonisti 1. Propranolol 2. Metoprolol 3. Atenolol 4. Bisprolol
-RGLVXSVWDQFHNRMHVDGUHMRG

2.

Mehanizam dejstva Inhibicija sinteze tiroidnih hormona blokadom oksidacije joda

Indikacije Primarni tretman autoimunskog hipertiroidizma; priprema za definitivnu terapiju autonomnog hipertiroidizma Dodatna terapija do postizanja
HX W RNVLQHPLMHRELQ RMHGLQDWHU DSLMD LU

8E O DDYDQMHWN LY QLK HIHNDWDWLURLGQ LK

hormona

tirotoksikoze u tiroiditisu

1. 2. 3. 4. 1. 2. 3.

Lugol ov rastvor
=DVLHQUDVWYR U.- 66. , ,RSDQRLQ DNLVHOLQD

$N XWQDLQKLELFLMDRVOREDDQMDWLURLGQ LK 3U L SUHPD] DRSHUDFLMXLXWLU RWRNVLQ RM

hormona (Wolff Chaikoff ljev efekat) krizi. Nije rutinska indikacija 1. Inhibicija transporta joda 1. i 2. nisu rutinska indikacija. 2. Inhibicijan sinteze tiroidnih WLURWRNVLQDNUL]DLHNVWUHPQRE ROQL hormona 3. Imunosupresija, inhibicija sekrecije subakutni tiroiditis. Nisu indikacija u
76+XEODDYDQMHWNLYQLKHIHN DWD KURQ L QRPW LURLGLW LVX

Natrijum iopanoat Kalijum perhlorat Litijum karbonat Glikokortikoidi

tiroidnih hormona

Opisane promene kod primene metimazola u vidu aplasia cutisQDMHHXYLGXSRMHGLQDQLKLOL multiplih leziMD RG  GR  FP QD NRL YUKD WHPHQD LOL SRWLOMNX MDYOMDMX VH L VSRQWDQR X  RG 
URHQLK XHVWDORVW RYH SURPHQH NRG SULPHQH PHWLPD]ROD QLMH RFHQMHQD 3RYH]DQRVW PHWLPD]ROD VD

veoma retkim teratogenim promenama nazvanim metimazolska embriopatija, (atrezija hoana ili
H]RIDJXVD QDHQD MH X  RG  GHWHWD LMH VX PDMNH X]LPDOH PHWLPD]RO RSWD XHVWDORVW RYLK

promena je 1 na 2500 za atreziju hoana do 1 na 10,000 za atreziju ezofagusa (23).

Opte je pravilo da, kada se hipermetabolizam trudnice stavi pod kontrolu, doza tionamida se
VPDQMXMH GR SRWUHEQH GD EL VH YUHGQRVWL VORERGQLK WLURLGQLK KRUPRQD X SOD]PL GUDOH X JRUQMHP RSVHJXLOLEODJRL]QDGJRUQMHJUDQLFH8WUHHPWURPHVHMXWUXGQRHGRWUXGQLFDSUHNLGDWHUDSLML

ali je posle porodjaja potrebQDYHOLNDRSUH]QRVW]ERJHVWHSRMDYHUHFLGLYDKLSHUWLURLGL]PD

2ED WLRQDPLGD VX GR]YROMHQD NRG PDMNL NRMH GRMH 3URSLOWLRXUDFLO VH L]OXXMH X POHNX SURVHQR  RG GDWH GR]H RGQRVQR X POHNX VH QDOD]L VDPR RNR  VLPXOWDQR RGUHHQH NRQFHQWUDFLMH

u serumu. Primera radi, ako majka uzima 600 mg propiltiouracila dnevno, ukupno 149 mikrograma
SUHOD]LXPOHNRWR]DEHEXRGNJ]QDLLVWRWRLGR]DRGPJ]DRVREXRGNJ

Pored toga prelazak tionamida kroz placentu i u mleko ne treba uvek posmatrati kao nepovoljnu okolnost. Poto TSHR At prolaze placentu i u mleko, mogla bi, ako su u visokom titru, da dovedu i do
SUROD]QH VWUXPH L KLSHUWLURLGL]PD SORGD 0DOH NROLLQH WLRQDPLGD NRMH SUROD]H SODFHQWX LOL X POHNR PRJXGDVSUHHRYXQHHOMHQXSRMDYX

Beta adrenergijski lekovi

%HWDDGUHQHUJLMVNLDQWDJRQLVWLVXYUORNRULVQDGRSXQDOHHQMXKLSHUWLURLGL]PDXUDQRMID]LEROHVWL

dok su vrednosti tiroksina u cirkulaciji poviene. Ovi lekovi ne deluju na uzrok hipertiroidizma ali
XEODDYDMX SRVOHGLFH VLPSDWLNR WRQLQRJ GHORYDQMD WLURLGQLK KRUPRQD3RWR WLRQDPLGL GHOXMX QD SURL]YRGQMX QRYLK NROLLQD KRUPRQD L QH XWLX QD SRVOHGLFH YH L]OXHQLK KRUPRQD X FLUNXODFLML

kombinacija beta blokatora koji deluju na simptome ali ne i na uzrok bolesti i tionamida koji deluju na
X]URN DOL QH L QD VLPSWRPH MH YUOR NRULVQD 3RG GHMVWYRP EHWD DQWDJRQLVWD XEODDYDMX VH WUHPRU SDOSLWDFLMH XVSRUDYD VH VUDQL ULWDP L ]QRMHQMH VH VPDQMXMH1HPD SRVHEQLK SUHGQRVWL]D ELOR NRML RG UDVSRORLYLKOHNRYDL]JUXSHEHWDDQWDJRQLVWDQHW MHEROMDVDUDGQMDNRGX]LPDQMDSUHSDUDWDVDGXLP R SROXLYRWRP]ERJHJDVHPRJXGDWLXMHGQRMGR]LGQHYQR3RWUHEQDMHSDQMDNRGOHHQMDEROHVQLNDVD VUDQRP LQVXILFLMHQFLMRP DN L DNR MH L]D]YDQD KLSHUWLURLGL]PRP 8 EROHVQLND VD UHVSLUDWRUQRP

opstrukciMRPLOLSRUHPHDMLPDVSURYRHQMDEHWDEORNDWRULQLVXGR]YROMHQL8RYLPRNR lnostima mogu se dati lekovi iz grupe antagonista fluksa kalcijuma (diltiazem ili verapamil). Lekovi iz ove grupe se
RELQRGDMXVDPRXSUYDWULPHVHFDOHHQMDGRNVHQHQRUPDOL]XMXYUHGQRVWLWLURNVLQDXFLUNODFLML

Neorganski jod
U farmakolokim dozama QHRUJDQVNLMRGLQKLELHRVOREDDQMHWLURLGQLKKRUPRQDXWRNXQHNROLNR dana do nekoliko nedelja. Poto je efekat kratkotrajan, jodidi se daju samo kao priprema za definitivnu WHUDSLMX RSHUDFLMRP LOL 326/( WHUDSLMVNH GR]H UDGLRMRGD GD EL VH XEU]DOR VQLDYDQM cirkulacijskih e
NRQFHQWUDFLMD WLURLGQLK KRUPRQD 8RELDMHQD GR]D /XJRO RYRJ UDVWYRUD  MRG X  UDVWYRUX NDOLMXPMRGLGDMHGRPOWULSXWDGQHYQR]DVLHQLUDVWYRUNDOLMXPMRGLGD66.,GDMHVHXGR]L

od 60 mg (jedna kap) dnevno.

Postupak u tokVLQRMQRGR]QRMVWUXPL
7RNVLQL SRMHGLQDQL LOL YLHVWUXNL QRGXVL VX PRJX X]URN KLSHUWLURLGL]PD RELQRXVUHGRYHQLK LOL VWDULMLK RVRED EH] RIWDOPRSDWLMH L HVWR VD L]UD]LWLP NDUGLRYDVNXODUQLP SURPHQDPD 'LMDJQR]D VH

postavlja fizikalnim nalazom jednog LOL YLH QRGXVD X WLWDVWRM OH]GL /DERUDWRULMVNL QDOD]L VH QL]DN TSH sa ili bez povienih vrednosti tiroidinih hormona. Nizak TSH i nodozna struma su indikacija za VFLQWLJUDILMXWLWDVWHOH]GHNRMRPVHSRWYUXMHMHGDQLOLYLHKLSHUIXQNFLMVNLKQRGXVD). 5
+LSHUWLURLGL]DP X WRNVLQRM QRGR]QRM VWUXPL MH DXWRQRPQD SRMDYD L ]ERJ WRJD VH QH PRH RHNLYDWLSRVWL]DQMHUHPLVLMHGHORYDQMHPWLRQDPLGD7LRQDPLGLVHRYGHPRJXGDWLQDMGXHWULPHVHFDX SULSUHPL ]D RSHUDWLYQR OHHQMH 3RWSXQR MH EHVPLVOHQR QHRSUDYGD R L WHWQR GXJRWUDMQR OHHQMH Q DXWRQRPQRJ KLSHUWLURLGL]PD PHGLNDPHQWQRP WHUDSLMRP 6ROLWDUQL KLSHUIXQNFLMVNL QRGXV MH QDMHH LQGLNDFLMD]DWHUDSLMVNXGR]XUDGLRMRGDGRNVHSROLQRGR]QDVWUXPDOHLRSHUDWLYQLPSXWHP8SULSUHPL

za definitivnu terapiju veoma su korisni beta adrenergijski antagonisti; oni su posebno korisni jer oko
 EROHVQLND VD WRNVLQRP QRGR]QRP VWUXPRP LPD SRUHPHDM ULWPD SR WLSX ILEULODFLMH SUHWNRPRUD

(26). Ako postoji fibrilacija pretkomora obavezna je antiagregaciona ili antikoagulantna terapija, zavisno od rizika trombogeneze(27).

3RVWXSDNXWLURWRNVLQRMID]LWLURLGLWLVD

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

mije.

3ULPHQDWLRQDPLGDELPRJODVDPRGDSURGXLLSURGXELKLSRWLURLGQXID]XLWLURLGLWLVDNRMDRELQRSUDWL WLURWRNVLQX ID]X .DR WR MH EHVPLVOHQR GDYDWL WLRQDPLGH LVWR WDNR QHPD QLNDNYRJ RSUDYGDQMD ]D

primenu glikokortikoida u prolaznim oblicima kao i

X KURQLQRP WLURLGLWLVX -HGLQL L]XWHWDN NDGD VH

PRH SULKYDWLWL NUDWNRWUDMQD SULPHQD PDOLK GR]D JOLNRNRUWLNRLGD MHHNVWUHPQREROQDID]D VXEDNXWQRJ WLURLGLWLVDDOLXWXWUHEDELWLYHRPDNULWLDQXRGOXFL]DVWHURLGH 7LURWRNVLQD ID]D WLURLGLWLVD MH REL

no kratkotrajna, najvie do nekoliko sedmica i prolazi bez

OHHQMD 8RELDMHQRWLURWRNVLQXID]XSUDWL SHULRGKLSRWLURLGL]PDNDGDMHPRJXHLGR]YROMHQRMHGDWL OHYRWLURNVLQXRHNLYDQMXRSRUDYNDWLURLGQRJWNLYDXSUROD]QLPREOLFLPDWLURLGLWLVD8KURLQRP Q WLURLGLWLVXOHYRWLURNVLQ VHSRWRMHXYHGHQRELQR GDMHWUDMQR+LSRWLURLGL]DPX WLURLGLWLVXWUXGQLFD L GRMLOMDREDYH]QRWUHEDVXSVWLWXLVDWLGR]DPDNRMHVXYHHRGGR]DSRWUHEQLK]DRSWXSRSXODFLMX

Literatura
1. 2. 3. 4.
7UERMHYL % 7LURLGQD OH]GD SDWRIL]LRORNH RVQRYH L NOLQLNL SULVWXS GUXJR L]PHQMHQR L GRSXQMHQR L]GDQMH*ODYD=DYRG]DXGEHQLNHLQDVWDYQDVUHGVWYD%HRJUDG

5.

6. 7. 8. 9.

10. 11.

12.

Kaplan MM: Clinical Perspectives in the Diagnosis of Thyroid Disease Clin Chemistry 1999. 45:8(B) 13771383. Demers, LM, Spencer, CA: Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease part 3 C. Thyrotropin/Thyroid Stimulating Hormone (TSH), 2002. http://www.nacb.org/ OLeary PC, Feddema PH, Michelangeli VP, Leedman PJ, Chew GT, Knuiman M, Kaye J, Walsh JP: Investigations of thyroid hormones and antibodies based on a community health survey: the Busselton thyroid study Clin Endocrinol 2006; 64 , 97104 Reinwein D, Benker G, Lazarus JH, Alexander WD, European Multicenter Study Group on Antithyroid Drug Treatment. A prospective randomized trial of antithyroid drug dose in Graves disease therapy. J Clin Endocrinol Metab 1993;76:1516-21. Mitsiades N, Poulaki V, Tseleni-Balafouta S, Chrousos GP, Koutras DA. Fas ligand expression in thyroid follicular cells from patients with thionamide-treated Graves disease. Thyroid 2000;10:527-532. Nicholas WC, Fischer RG, Stevenson RA, Bass JD. Single daily dose of methimazole compared to every 8 hours propylthiouracil in the treatment of hyperthyroidism. South Med J 1995;88:973-976 Reinwein D, Benker G, Lazarus JH, Alexander WD. A prospective randomized trial of antithyroid drug dose in Graves disease therapy. J Clin Endocrinol Metab 1993;76:1516-1521. Homsanit M, Sriussadaporn S, Vannasaeng S, Peerapatdit T, Nitiyanant W, Vichayanrat A. Efficacy of single daily dosage of methimazole vs. propylthiouracil in the induction of euthyroidism. Clin Endocrinol (Oxf) 2001;54:385-390. He CT, Hsieh AT, Pei D, et al. Comparison of single daily dose of methimazole and propylthiouracil in the treatment of Graves hyperthyroidism. Clin Endocrinol (Oxf) 2004;60:676-681 Hegeds L, Hansen JM, Bech K, et al. Thyroid stimulating immunoglobulins in Graves disease with goitre growth, low thyroxine and increasing triiodothyronine during PTU treatment. Acta Endocrinol (Copenh) 1984;107:482-488. Allannic H, Fauchet R, Orgiazzi J, et al. Antithyroid drugs and Graves disease: a prospective randomized evaluation of the efficacy of treatment duration. J Clin Endocrinol Metab 1990;70:675-679.

13.

14. 15.

16. 17.

18. 19.

20.

21. 22. 23. 24. 25. 26. 27.

Razvi S, Vaidya B, Perros P,Pearce SHS: What is the evidence behind the evidence-base? The premature death of block-replace antithyroid drug regimens for Graves disease European Journal of Endocrinology (2006) 154 783786 Maugendre D, Gatel A, Campion L, et al. Antithyroid drugs and Graves disease prospective randomized assessment of long-term treatment. Clin Endocrinol (Oxf) 1999;50:127-132. Hashizume K, Ichikawa I, Sakurai A, et al. Administration of thyroxine in treated Graves disease: effects on the level of antibodies to thyroid-stimulating hormone receptors and on the risk of recurrence of hyperthyroidism. N Engl J Med 1991;324:947-953. McIver B, Rae P, Beckett G, Wilkinson E, Gold A, Toft A. Lack of effect of thyroxine in patients with Graves hyperthyroidism who are treated with an antithyroid drug. N Engl J Med 1996;334:220-224. Rittmaster RS, Zwicker H, Abbott EC, et al. Effect of methimazole with or without exogenous L-thyroxine on serum concentrations of thyrotropin (TSH) receptor antibodies in patients with Graves disease. J Clin Endocrinol Metab 1996;81:3283-3288 Pfeilschifter J, Zeigler R. Suppression of serum thyrotropin with thyroxine in patients with Graves disease: effects on recurrence of hyperthyroidism and thyroid volume. Eur J Endocrinol 1997;136:81-86. Cho BY, Shong MH, Yi KH, Lee HK, Koh CS, Min HK. Evaluation of serum basal thyrotrophin levels and thyrotrophin receptor antibody activities as prognostic markers for discontinuation of antithyroid drug treatment in patients with Graves disease. Clin Endocrinol (Oxf) 1992;36:585-590. Cooper DS. Antithyroid drugs for the treatment of hyperthyroidism caused by Graves disease. Endocrinol Metab Clin North Am 1998;27:225-247.Vanderpump MP, Ahlquist JA, Franklyn JA, Clayton RN. Consensus statement for good practice and audit measures in the management of hypothyroidism and hyperthyroidism: the Research Unit of the Royal College of Physicians of London, the Endocrinology and Diabetes Committee of the Royal College of Physicians of London, and the Society for Endocrinology. BMJ 1996;313:539-544. Sheng WH, Hung CC, Chen YC, et al. Antithyroid-drug-induced agranulocytosis complicated by lifethreatening infections. QJM 1999;92:455-461. Andres E, Kurtz JE, Perrin AE, Dufour P, Schlienger JL, Maloisel F. Haematopoietic growth factor in antithyroid-drug-induced agranulocytosis. QJM 2001;94:423-428. Julia A, Olona M, Bueno J, et al. Drug-induced agranulocytosis: prognostic factors in a series of 168 episodes. Br J Haematol 1991;79:366-371. Tajiri J, Noguchi S, Okamura S, et al. Granulocyte colony-stimulating factor treatment of antithyroid druginduced granulocytopenia. Arch Intern Med 1993;153:509-514. Fukata S, Kuma K, Sugawara M. Granulocyte colony-stimulating factor (G-CSF) does not improve recovery from antithyroid drug-induced agranulocytosis: a prospective study. Thyroid 1999;9:29-31. Liaw Y-F, Huang M-J, Fan K-D, Li K-L, Wu S-S, Chen T-J. Hepatic injury during propylthiouracil therapy in patients with hyperthyroidism. Ann Intern Med 1993;118:424-428. Gurlek A, Cobaukara V, Bayraktar M. Liver tests in hyperthyroidism: effect of antithyroid therapy. J Clin Gastroenterol 1997;24:180-183.

28. Williams KV, Nayak S, Becker D, Reyes J, Burmeister LA. Fifty years of experience with propylthiouracil-associated hepatotoxicity: what have we learned? J Clin Endocrinol Metab 1997;82:1727-1733.