Reading"Assignment" Supervisor":"

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Divisi"EndokrinologiTMetabolik""
dr."Dharma"Lindarto,"Sp.PDTKEMD"
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HIPERTIROID!SUBKLINIS!:!PATOGENESIS!KELAINAN!KARDIOVASKULER!!

Andri"Iskandar"Mardia"
Divisi"Endokrin"Metabolik""Departemen"Ilmu"Penyakit"Dalam"
Fakultas"Kedokteran"Universitas"Sumatera"Utara"
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PENDAHULUAN!!

Disfungsi"tiroid"subklinis"yang"meliputi"hipotiroid"subklinis"dan"hipertiroid"subklinis"merupakan"
masalah"klinis"yang"menimbulkan"perdebatan"baik"menyangkut"masalah"screening,"diagnostik,"
kelainan"yang"ditimbulkan,"evaluasi"dan"penatalaksanaan.""

Hipertiroid" subklinis" diartikan" sebagai" didapatkannya" kadar" hormon" tirotropin" (TSH)" dibawah"
normal,"tetapi"kadar"hormon"tiroksin"(T4)"dan"triiodotironin"(T3)"bebas"yang"masih"dalam"batas"
normal."1,2"

Di" Amerika" Serikat" angka" kejadian" hipertiroid" subklinis" jika" menggunakan" batas" bawah" TSH"
kurang"dari"0,4mIU/L"didapatkan"33,2%"populasi."Bila"diagnosis"dibatasi"dengan"kadar"TSH"<0,1"
mIU/L," prevalensinya" menjadi" tinggal" 0,7%." " Hipertiroid" subklinis" sering" dijumpai" pada" pasien"
yang"mendapat"terapi"dengan"levotiroksin,"yaitu"sekitar"14T21%."2"

Madhukar" dkk," melakukan" penelitian" di" Dhulikhel" HospitalTKathmandu" University" Hospital"""

untuk" melihat" prevalensi" kelianan" tiroid" ," diperoleh" prevalensi" total" hipertiroid" 9%" dengan"
hipertiroid" yang" nyata" 3%" dan" hipertiroid" subklinis" sebesar" 6%," dengan" nilai" normal" yang"
digunakan"pada"penelitian"berturutT"turut":"fT3,"fT4"dan"TSH"adalah"1.4TT4.2"pg/ml,"0.8TT2.0"ng/dl"

dan"0.4TT6.0"IU/ml."selain"itu"diiperoleh"perempuan"lebih"banyak"dari"lakiTlaki"dan"dengan"usia"
dengan"prevalensi"tertinggi"15T30"tahun."3"

Sampai"sekarang"tidak"ada"informasi"yang"definitif"tentang"insidensi"hipertiroid"subklinis"pada"
populasi" umum." Rentang" insidensinya" 0,6%" sampai" 16%," terganung" kriteria" diagnostic" dan""
1"

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sensitivitas" pengukuran" kadar" TSH." Penelitian" prospektif" pada" pasien" dengan" hipertiroid"
subklinis"endogen"diperoleh"hampir"50%"kasus"kadar"TSH"nya"akan"menjadi"normal"dan"sekitar"
5%"pertahun"akan"menjadi"hipertiroid"yang"nyata.4"

Penelitian" oleh" Vadiveloo" dkk," Perubahan" hipertiroid" subklinis" menjadi" hipertiroid" yang" nyata"
setelah"1"tahun"diagnosis"sekitar"10%"dengan"kadar"TSH"awal"<0,1"mU/L."pada"pasien"dengan"
TSH" <0,1mU/L" akan" memerlukan" pengobatan" hipertiroid" 17%" kasus" setalah" 2" tahun," 37%"
setelah" 5" tahun" dan" 44%" setelah" 7" tahun." Sedangkan" pada" pasien" dengan" kadar" TSH" 0.1" T0.4"
mU/L," 2.5%," 11%," dan" 17%" akan" memerlukan" pengobatan" untuk" hipertiroidnya" setelah" 2," 5,"
dan7"tahun."5"

Dalam" penelitian" yang" melibatkan" 1191" pasien" berusia" 60" tahun" atau" lebih," pada" kelompok"
yang" kadar" TSH" nya" rendah" (hipertiroid" subklinis)" dan" sedang" dalam" terapi" levotiroksin,"
mortalitas" dalam" 10" tahun" meningkat" 2" kali" lipat." Peningkatan" mortalitas" terutama" akibat"
kelianan"kardiovaskuler.2""

MetaTanalisis"oleh"Paul"dkk,"terdapat"hubungan"yang"lemah"antara"hipertiroid"subklinis"dengan"
kejadian" coronary' heart' disease" dan" kematian" dengan" relative" risk" untuk" coronary" heart"
disease,"mortalitas"kardiovaskuler"dan"keseluruhan"berturutTturut"1,2;"1,2;"dan"1,2."14"

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DEFINISI!!

Hipertiroid"subklinis"didefinisikan"sebagai"kadar"hormon"tirotropin"(TSH)"dibawah"normal"atau"
tidak" terdeteksi" dengan" kadar" hormon" tiroksin" (T4)" bebas" dan" triiodotironin" (T3)" bebas" yang"
masih"dalam"batas"normal."1,2,4"

Definisi"hipertiroid"subklinis"adalah"berdasarkan"laboratorium"bukan"klinis."Kadar"hormon"tiroid"
meningkat" walaupun" masih" dalam" rentang" normal" nilai" laboratorium" untuk" individu" dengan"
kadar" TSH" yang" rendah" atau" tidak" terdeteksi" tersebut," dan" akan" mengalami" mild' tissue'
hipertiroid."Nilai"normal"fungsi"tiroid"yang"berdasarkan"populasi"(population3based)"dapat"tidak"
menggambarkan" fungsi" tiroid" pada" individu" yang" diperiksa." Walaupun" demikian" diagnosis"
2"

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hipertiroid" subklinis" dan" hipertiroid" yang" nyata" berdasarkan" posisi" kadar" hormon" tiroid" pada"
rentang"normal"populasi.""4"

Berdasarkan"kadar"TSH"hipertiroid"subklinis"dapat"dibedakan;"dengan"kadar"TSH"rendah"namun"
masih" terdeteksi" (TSH" 0,1T0,4mU/L)" dan" dengan" kadar" TSH" yang" tidak" terdeteksi" (TSH" <0,1"
mU/L)." Progresivitas" menjadi" hipertiroid" yang" nyata" lebih" rendah" pada" penderita" hipertiroid"
subklinis"dengan"kadar"TSH"yang"rendah"dibandingkan"dengan"kadar"TSH"yang"tidak"terdeteksi."

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ETIOLOGI!DAN!DIFFERENTIAL!DIAGNOSIS!

Penyebab" utama" hipertiroid" subklinis" sama" dengan" hipertiroid" yang" nyata." Adanya" supresi"
terhadap"kadar"TSH"dapat"disebabkan"kelainan"nonTtiroid,"steroid"atau"dopamine"dan"lainnya."
Berdasarkan"penyebabnya","hipertiroid"subklinis"dapat"dibedakan"menjadi";2,4,14,6"

a. Hipertiroid"subklinis"endogen"

Penyebab"paling"sering"adalah"goiter"multinoduler,"tiroid"adenoma,"penyakit"grave.""

b. Hipertiroid"subklinis"eksogen""

Pasien" yang" menggunakan" hormon" tiroid" beresiko" untuk" menderita" hipertiroid"

subklinis," baik" karena" terapi" dengan" tiroid" hormon" yang" berlebihan" atau" karena"
supresi"TSH"yang"disengaja.""

Selain"akibat"hipertiroid"subklinis,"kadar"TSH"yang"rendah"dapat"juga"dijumpai"yang"tidak"terkait"
dengan" hipertiroid" subklinis" seperti" :" hipotiroidisme" sentral," non3tiroidal' illness" yang" berat,"
terapi"dengan"glukokortikoid,"amiodaron,"dopamine"atau"akibat"kesalahan"labolatorium."Oleh"
karena"itu,"anamnesa"yang"detail,"pemeriksaan"yang"teliti,"dan"gambaran"fungsi"hormon"tiroid"
dapat"membantu"mendiagnosis"hipertiroid"subklinis.""

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 Tabel"1."Etiologi"Hipertiroid"Subklinis4"

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GAMBARAN!KLINIS!!

Penurunan"sekresi"TSH"merupakan"pertanda"Hipertiroid"subklinis,"tetapi"peningkatan"hormon"
tiroid"bebas"menekan"sekresi"TSH"dan"menyebabkan"keluhan"tirotoksikosis"serta"berpengaruh"
terhadap" jaringan" lain." Pada" Hipertiroid" subklinis" pengaruh" tersebut" kurang" menonjol"
dibandingkan"dengan"pengaruh"pada"hipertiroid"yang"nyata.""

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Beberapa"pengaruh"hipertiroid"subklinis"pada"jaringan"tubuh":"

a. Metabolism"tulang"

Perubahan"yang"dapat"dijumpai"pada"penderita"hipertiroid"subklinis"antara"lain"densitas"
tulang" yang" menurun," marker" biokimia" metabolisme" tulang" meningkat," serum"
osteocalsin"meningkat,"ekspresi"hydroxyprolin"urin"meningkat."2,6"

Uzzan"dkk,"menemukan"adanya"densitas"tulang"pada"femoral'neck"dan"radius"signifikan"
lebih"rendah"pada"penderita"hipertiroid"subklinis"dari"pada"kelompok"normal."6"

Bauer"dkk,"resiko"fraktur"pada"panggul"meningkat"3"kali"lebih"tinggi"dan"fraktur"vertebra"
4,4" kali" lebih" tinggi" pada" wanita" dengan" kadar" TSH" <0,1" mU/L" dibandingkan" dengan"
normal"TSH."6"

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 b. Abnormalitas"neuropsikiatri"

Penderita" hipertiroid" subklinis" akan" mengalami" perasaan" takut," tidak" ramah," mudah"
marah,"dan"tidak"mampu"untuk"berkonsentrasi."Rotterdan"studi"memperoleh"dari"1843"
pasien" hipertiroid" subklinis" endogen" dengan" usia" lebih" dari" 55" tahun," angka" kejadian"
demenzia""dan"Alzheimer"meningkat"3"kali"dengan"kadar"TSH"<"0,4mU/L."6"

c. Kelainan"kardiovaskuler"

Berdasarkan" Framingham" study," insidensi" kumulatif" atrial" fibrilasi" pada" 10" tahun" pada"
penderita" dengan" usia" >60" tahun" adalah" 28%" pada" kondisi" TSH" <0,1mU/L," dengan"
relative"risk"ratio"3,1"jika"dibandingkan"orang"normal."6"

Pengaruh"lainnya"dapat"berupa"kadar"kolesterol"total"dan"LDL"yang"menurun,"alanin"tranferase,"
glutation"transferase"dan"gamma"GT"yang"meningkat,"serum"sex"hormon"binding"globulin"yang"
meningkat,"dan"waktu"tidur"malam"menurun."2"

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EFEK!HORMON!TIROID!PADA!SISTEM!KARDIOVASKULER!

Mekanisme" molekuler" pengaruh" hormon" tiroid" terhadap" sistem" kardiovaskuler" yang" terjadi"
pada" cardiomiosit" dapat" melalui" jalur" genomic" dan" nongenomic." Efek" genomic" melalui"
transcripsi"aktivasi"atau"represi"dari"target"gen"spesifik"yang"mengkode"protein"struktural"dan"
fungsional"cardiomiosit."Proses"ini"dimulai"dengan"masuknya"T3,"bentuk"aktif"hormon"tiroid,"ke"
cardiomiosit"melalui"transfort"spesifik"pada"membran"sel."Pada"cardiomiosit"T3"akan"memasuki"
nucleus" dan" berinteraksi" dengan" spesifik" transcriptional" activators" (nucleus" reseptor" α1)" atau"
represor"(nucleus"reseptor"α2),"sehingga"akan"mempengaruhi"sintesis"protein.7"

Dari" sekian" banyak" protein" yang" terbentuk," yang" paling" khas" adalah" myosin' heavy' chain," dan"
protein"reticulum"sarkoplasmik"yang"berperan"dalam"regulasi"ikatan"calcium"intraseluler,"yang"
disebut"dengan"calcium"activates"ATPase"dan"kofaktor"inhibitornya,"phospholamban."Pengaruh"

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perubahan"myosin"heavy"chain"masih"belum"jelas."Akan"dijumpai"peningkatan"α'myosin'chain,"
yang"merupakan"myosin"yang"cepat,"dan"penurunan"β'myosin'chain,"yang"bekerja"lambat.9""

Sarcoplasmic" reticulum" calciumTactivated" ATPase" berperan" dalam" mengatur" reuptake" calcium"

kedalam" lumen" reticulum" sarkoplasmik" selama" diastol," hal" ini" merupakan" penentu" kecepatan"
relaksasi" miokardium" setelah" kontraksi." Walaupun" demikian" terdapat" kofaktor" inhibitor" yaitu"
phospolamban," yang" bila" ekspresinya" meningkat" akan" menekan" aktivitas" dari" Sarcoplasmic"
reticulum" calciumTactivated" ATPase." Hormon" tiroid" berperan" dalam" upregulasi" Sarcoplasmic"
reticulum" calciumTactivated" ATPase" dan" downregulasi" phspholamban," dengan" demikian" akan"
meningkatkan"relaksasi"miokardium."Perbaikan"dalam"calcium"reuptake"selama"diastolik"dapat"
menghasilkan"kontaktilitas"miokard"yang"baik."8,9"

Reseptor" β" adrenergik" dan" Na+/K+" ATPase" juga" diregulasi" oleh" hormone" tiroid." Adanya"
peningkatan" stimulasi" β" adrenergik" akibat" peningkatan" second" messenger," cAMP," yang" akan"
meningkatkan"heart"rate."9"

Selain" memodifikasi" protein" tersebut" diatas," hormon" tiroid" juga" memodifikasi" ekpresi" ion"
channels" seperti" NA+/K+' activated' ATPase,' voltage3gated' K+' channels,' Na+/Ca+' exchanger,"
dengan"demikian"akan"mempengaruhi"respon"elektrokimia"dan"meakanikal"miokardium.""

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Gambar"1."Genomic"Efek"Hormon"Tiroid8"

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Disamping" efek" genomic," hormon" tiroid" juga" mempengaruhi" inotropik" dan" kronotropik" dari"
miokardium" lebih" cepat" dari" efek" genomic." Mekanisme" ini" disebut" mekanisme" nongenomic."
Hormone"tiroid"menyebabkan"penurunan"resistensi"arteriol"perifer"dengan"efek"langsung"pada"
relaksasi""vascular'smotth'muscle"(VSM)"dan"menyebabkan"penurunan"mean"arterial"pressure,"
yang"akan"merangsang"sistem"renninTangiotensinTaldosteron"dan"peningkatan"retensi"nartium."
Hormone"tiroid"juga"meningkatkan"sintesis"eritropoietin,"yang"akan"meningkatkan"hemoglobin."
Perubahan" ini" akan" mengakibatkan" peningkatan" preload" dan" volume" darah" yang" akan"
meningkatkan"cardiac"output."6,8,9"

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Relaksasi"VSM"dapat"melalui"efek"genomic"dan"nongenomic."Melalui"efek"nongenomic"berupa"
perubahan" channel" ion" pada" membrane" sel" dan" peningkatan" sintesisi" nitric" oxide" endothelial"
yang"akan"merelaksasi"VSM."9"

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Gambar"2."Efek"Hormon"tiroid"pada"hemodinamik6"

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FATOGENESIS!KELAINAN!KARDIOVASKULER!!

Kelebihan"hormon"tiroid"pada"hipertiroid"subklinis"menyebabkan"kelainan"kardiovaskuler"yang"
bervariasi." Kelainan" tersebut" dapat" diakibatkan" langsung" atau" tidak" langsung" hormon" tiroid"
pada" sistem" kardiovaskuler," dan" efek" yang" diperantarai" aktivasi" neurohormonal." Resiko"
kardiovaskuler"pada"hipertiroid"subklinis"dapat"dibagi"menjadi"efek"jangka"pendek"akibat"efek"
elektrofisiologi"dari"hormon"tiroid"dan"efek"jangka"panjang"akibat"peningkatan"left'ventricular'
mass"atau"hipertropi"ventrikel"kiri"serta"peningkatan"cardiac'workload."4,8,10"

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 Tabel"2."Resiko"kelainan"Kardiovaskuler"pada"Hipertiroid"Subklinis4"

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Abnormalitas" kardiovaskuler" sama" pada" pasien" dengan" hipertiroid" subklinis" endogen" dan"
eksogen."4"

Pada"banyak"penelitian,"pasien"dengan"hipertiroid"subklinis"memiliki"heart"rate"yang"lebih"tinggi"
dan"meningkatnya"prevalensi"supraventrikular"aritmia." 3"sebuah"penelitian"cross"sectional"yang"
membandingkan" prevalensi" atrial" fibrilasi" (AF)" pada" 1338" pasien" dengan" hipertiroid" subklinis"
dan" yang" nyata" akibat" nodul" tiroid" atau" penyakit" grave" dengan" 22300" kontrol" pasien" yang"
datang" berobat" ke" rumah" sakit;" diperoleh" hasil" prevalensi" AF" 13,8%" pada" hipertiroid" yang"
nyata,"12,7%"pada"hipertiroid"subklinis,"dan"2,3"%"pada"kelompok"kontrol"dengan"relative"risk"
(RR)" untuk" AF" adalah" 5,2" dibandingkan" kontrol." Dengan" demikian" pasien" dengan" hipertiroid"
subklinis"berhubungan"dengan"peningkatan"kejadian"AF""sebesar"5"kali.11"

Pada" penelitian" yang" dilakukan" Kwon" dkk," kadar" TSH" yang" rendah" signifikan" berhubungan"
dengan" paroxysmal" AF" pada" semua" kelompok" umur," dan" kadar" TSH" <" 1,5mU/L" dapat"
merupakan"factor"resiko"untuk"terjadinya"AF.11"

Adanya"AF"merupakan"factor"resiko"independent"terjadinya"stroke,"angina"pectoris,"congestive"
heart"failure,"dan"berhubungan"dengan"peningkatan"2"kali"lebih"banyak"kematian."4"

Mekanisme" adanya" kecendrungan" adanya" aritmia" seperti" AF" pada" hipertiroid" subklinis,"
kemungkinan" besar" disebabkan" peningkatan" excitability" atrial" dan" pemendekan" periode"
refraktor" dari" jaringan" konduksi." Selain" itu" dapat" juga" akibat" peningkatan" tekanan" atrium" kiri"
akibat" hipertropi" ventrikel" kiri," iskemik" akibat" peningkatan" resting' heart' rate," peningkatan"

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aktivitas"atrial"ectopik".8" Selain"itu"dapat"juga"diakibatkan"adanya"hyperadrenergic"state,"yang"
pada"mengakibatkan"peningkatan"sensitivitas"jantung"terhadap"stimulasi"adrenergik.9,10"

Abnormalitas"kardiovaskuler"yang"paling"konsisten"dijumpai"pada"hipertiroid"subklinis"baik"yang"
endogen" maupun" yang" eksogen" adalah" peningkatan" left' ventricular' mass" dengan" tidak" ada"
perubahan"maupun"dengan"perubahan"pada"fungsi"sistolik"saat"istirahat"dan"biasanya"dijumpai"
dengan"gangguan"fungsi"diastolik."Hal"ini"akan"berakhir"menjadi"heart"failure."4,9,10"

Dengan" menggunakan" ekokardiografi" pada" 60" pasien" dengan" hipertiroid" subklinis" eksogen,"
didapatkan" peningkatan" indeks" massa" ventrikel" kiri" dibandingkan" kelompok" kontrol.4"
peningkatan" massa" ventrikel" kiri" lebih" berhubungan" dengan" lamanya" hipertiroid" subklinis"
dibandingakan" dengan" kadar" hormon" tiroid" " dan" dapat" dicegah" dengan" pemberian" obat"
penyekat"β"adrenergik.2,11""Dapat"diasumsikan"abnormalitas"kardiovaskuler"merupakan"respon"
terhadap"adanya"overload"kronik"hemodinamik"akibat"adanya"“mild'hyperkinetic'cardiovascular'
state”.'

Mekanisme"yang"bertanggung"jawab"terhadap"terjadinya"hipertrofi"ventrikel"kiri"dan"disfungsi"
diastolik"pada"hipertiroid"subklinis"endogen"maupun"eksogen"masih"belum"jelas."Hipertrofi"dan"
disfungsi"diastolik"merupakan"pertanda"adanya"cronik"hemodinamik"overload,"yang"disebabkan"
perubahan" molekuler" jantung" yang" berupa" peningkatan" sintesis" protein" kontraktil" dan"
penurunan" aktivitas" sarkoplasmic" reticulum" calcium" ATPase." Hal" ini" akan" mengakibatkan"
perlambatan" dari" frekuensi" relaksasi" " dan" memperburuk" pengisian" ventrikel." Mekanisme" ini"
bertentangan"dengan"kerja"hormon"tiroid"pada"miosit."Hal"ini"dapat"dijelaskan"dengan,"dalam"
jangka" panjang," efek" dari" hormon" tiroid" yang" awalnya" memberi" efek" positif" menjadi" efek"
negatif" akibat" peningkatan" kronik" kerja" sarkoplasmic" reticulum" calcium" ATPase" sehingga"
mengalami"perubahan."4,8"
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Smit" dkk," melakukan" penelitian" terhadap" pasien" dengan" hipertiroid" subklinis" eksogen" yang"
telah" menjadi" eutiroid" diperoleh" bahwa" disfungsi" diastolik" dapat" kembali" membaik" setelah"
pasien"menjadi"eutiroid.9" Tsarouhas"dkk"melaporkan"satu"kasus,"pasien"yang"telah"mengalami"

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kardiomiopati" dilatasi" akibat" hipertiroid" subklinis" tanpa" adanya" penyebab" kalainan"
kardiovaskular" lainnya," setelah" terapi" (furosemide," carvedilol," angiotensinTconvertingTenzyme"
inhibitor"dan"thiamazole)"selama"6"bulan"dilatasi"kardiomiopati"nya"reversible.'12'
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PENGOBATAN!!

Hipertiroid!Subklinis!Eksogen!

Kecuali"pasien"dengan"kanker"tiroid"sebelumnya,"dimana"diperlukan"supresi"thyrotropin,"dosis"
thyroxine"dikurangi"jika"terjadi"hipertiroid"subklinis."Walaupun"dosis"sudah"dikurangi,"kadar"TSH"
biasa"tetap"rendah"selama"6"sampai"8"minggu."7"
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Hipertiroid!Subklinis!Endogen!!

Pemberian" pengobatan" pada" hipertiroid" subklinis" masih" kontroversi." American" association" of"
clinical"endocrinologists"(AACE)"merekomendasikan"pemeriksaan"klinis"dan"laboratorium"secara"
periodik" untuk" memantau" fungsi" hormon" pada" penderita" hipertiroid" subklinis." Jika" tetap"
rendah,"baru"dipertimbangkan"untuk"diterapi.""

Pada" hipertiroid" subklinis" tanpa" komplikasi" akibat" kelebihan" hormon" tiroid" dan" kadar" TSH"
dibawah"nilai"normal,"terapi"tidak"diperlukan,"tetapi"fungsi"tiroid"diperiksa"secara"periodik."5,6"

Pasien"dengan"hipertiroid"subklinis"dengan"gejala"hipertiroid,"AF,"kehilangan"berat"badan"tanpa"
sebab" lain," wanita" dengan" osteopenis" atau" osteoporosis," pasien" dengan" goiter" multinodul"
sebaiknya"diterapi.6,7"

Pada" beberapa" pasien," terapi" dengan" obat" antitiroid" dosis" rendah" selama" 6T12" bulan"
memberikan"respon"yang"bagus."Methimazole"5T10"mg"perhari"atau"propiltiourasil"50T100"mg"
per" hari" dapat" diberikan." Penghentian" obat" dilakukan" setelah" 6T12" bulan" terapi." Jika" dijumpai"
kekambuhan"kembali"setelah"penghentian"terapi"dapat"diulangi"lagi"dengan"obat"antitiroid"atau"
pengobatan"definitif"dengan"iodine"ablasi."6,7"

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Gambar"3."Algoritme"Pengobatan"Hipertiroid"Subklinis6,7"
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Pengobatan!Kelainan!Kardiovaskular!

Penurunan" rataTrata" heart" rate" dalam" 24" jam," denyut" arterial" premature," hipertrofi" ventrikel"
kiri" dijumpai" pada" hipertiroid" subklinis" endogen" yang" telah" mengalami" eutiroid" dengan" terapi"
methimazole." Terapi" antitiroid" memberikan" keuntungan" mengembalikan" ritme" sinus" pada"
pasien"tua"dengan"hipertiroid"subklinis."4"

Pada" pasien" dengan" hipertiroid" subklinis" eksogen," penambahan" β" bloker" kardioselektif,"
bisoprolol,"terhadap"terapi"levotiroksin"selama"6"bulan"secara"signifikan"menurunkan"kejadian"
supraventrikular" aritmia," menurunkan" rataTrata" heart" rate," dan" left" ventricular" mass," dengan"
memperbaiki"fungsi"diastolik"saat"istirahat"dan"funsi"sistolik"saat"beraktivitas."4"

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KESIMPULAN!!

Hipertiroid" subklinis" merupakan" kelianan" yang" sering" dijumpai." Penyebab" hipertiroid" subklinis"
dapat" eksogen" maupun" endogen." hipertiroid" subklinis" eksogen" banyak" dijumpai" pada" terapi"
supresi" TSH" dengan" levotiroksin," hipertiroid" subklinis" endogen" seperti" goiter" endemic."
Hipertiroid" subklinis" menyebabkan" kelainan" pada" berbagai" sistem" organ" seperti" menggangu"
metabolism"tulang,"sistem"kardiovaskuler,"abnormalitas"neuropsikiatri."

Gangguan" kardiovaskuler" pada" hipertiroid" subklinis" dapat" berupa" peningkatan" heart" rate,"
peningkatan"resiko"supraventrikular"arritmia,"atrial"fibrilasi,"peningkatan"left'ventricular'mass,"
yang"sering"disertai"dengan"disfungsi"diastolik"dan"terkadang"disfungsi"sistolik.""

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DAFTAR!PUSTAKA!!

1. Yunir" M," Disfungsi" Tiroid" Subklinis" :" Hipotiroid" Subklinis" dan" Hipertiroid" Subklinis,"
Penatalaksanaan" PenyakitTPenyakit" Tiroid" Bagi" Dokter," Perkumpulan" Endokrinologi"
Indonesia,"Pusat"Penerbitan"Departemen"Ilmu"Penyakit"Dalam,"Nov,"2008;"h:"44T8"

2. Soeatmadji"D"W,"Disfungsi"Tiroid"Subklinis":"Hipotiroidisme"Subklinis"dan"Hipertiroidisme"
Subklinis," Buku" Ajar" Tiroidologi" Klinik," Badan" Penerbit" Universitas" Diponegoro,"
Semarang,"2007;"h:473T93"

3. Aryal" Madhukar" et" al," A" prevalence" of" thyroid" dysfunction" in" Kathmandu" University"
Hospital,"Nepal","Biomedical"Research,"2010"

4. Biondi" B," et" al," Subclinical" Hyperthyroidism" :" Clinical" Features" and" Treatment" Options,"
Europian"Journal"of"Endocrinology,"2005;"p:1T9"

5. Vadiveloo"et"al,"The"Thyroid"Epidemiology,"Audit,"and"Research"Study"(TEARS):"Natural"
History"of"Subclinical"Hyperthyroid,""Journal"Clin"Endocrinol"Metan,"2010.""
6. Gul" Oz" Serife," Kilicarslan" Alpaslan," Sbublinical" Hyperthyroidism," Journal" of" Ankara"
Medical"School,"vol"25,"Jan,"2004;"p:191T8"

7. Shrier" D," Burman" K," Subclinical" Hyperthyroidsm" :" Controversies" in" Management,"
American"of"Family"Physicians,"2002;"p:431T8"

8. Fazio" et" al," Effects" of" Thyroid" Hormon" on" the" Cardiovascular" Sistem," Endocrine" socity,"
2004"

9. Klein"I,"Danzi"S,"Thyroid"Disease"and"the"Heart,"Circulation,"2007"

10. Kahaly,"Dillmann,"Thyroid"Hormone"Action"in"the"Heart,"Endocrine"Reviews,"2005""

11. Dabrowa" et" al," The" mechanisms" of" atrial" fibrillation" in" hyperthyroidism," Thyroid"
Research,"2009"

12. Tsarouhas"et"al,"Reversible"Dilated"Cardiomyopathy"Due"to"Subclinical"Hyperthyroidism,"
Hellenic"Journal"Cardiol,"2010"

13. Smit" et" al," Reversible" Diastolik" Dysfunction" after" LongTTermExogenous" Subclinical"
Hyperthyroidism:" A" Randomized," PlaceboTKontrolled" Study," J" Clin" Endocrinol" Metab,"
2005"

14. Ladenson" Paul," Cardiovascular" Conseuences" of" Subclinical" Thyroid" Dysfunction" :" More"
Smoke"But"No"Fire,"Annals"of"Internal"Medicine,"2008"

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