Slide 1
Hyperthiroidism
ThyroidLargest Endocrine organ in the bodyInvolved in
production, storage, and release of thyroid hormoneFunction
influenced byCentral axis (TRH)Pituitary function (TSH)Comorbid
diseases (Cirrhosis, Graves, etc.)Environmental factors (iodine
intake)Thyroid (cont)Regulates basal metabolic rateImproves cardiac
contractilityIncreases the gain of catecholaminesIncreases bowel
motilityIncreases speed of muscle contractionDecreases cholesterol
(LDL)Required for proper fetal neural growthThyroid
PhysiologyUptake of Iodine by thyroidCoupling of Iodine to
ThyroglobulinStorage of MIT / DIT in follicular spaceRe-absorption
of MIT / DITFormation of T3, T4 from MIT / DITRelease of T3, T4
into serumBreakdown of T3, T4 with release of IodineIodine
uptakeNa+/I- symport protein controls serum I- uptakeBased on
Na+/K+ antiport potentialStimulated by TSHInhibited by
Perchlorate
MIT / DIT formationThyroid Peroxidase (TPO)Apical membrane
proteinCatalyzes Iodine organification to Tyrosine residues of
ThyroglobulinAntagonized by methimazoleIodine coupled to
ThyroglobulinMonoiodotyrosine (Tg + one I-)Diiodotyrosine (Tg + two
I-)Pre-hormones secreted into follicular spaceSecretion of Thyroid
HormoneStimulated by TSHEndocytosis of colloid on apical
membraneCoupling of MIT & DIT residuesCatalyzed by TPOMIT + DIT
= T3DIT + DIT = T4Hydrolysis of ThyroglobulinRelease of T3,
T4Release inhibited by Lithium10Thyroid Hormones
11Thyroid HormoneMajority of circulating hormone is T498.5%
T41.5% T3Total Hormone load is influenced by serum binding proteins
(TBP, Albumin, ??)Thyroid Binding Globulin 70%Albumin
15%Transthyretin 10%Regulation is based on the free component of
thyroid hormone
12Hormone Binding FactorsIncreased TBGHigh estrogen states
(pregnancy, OCP, HRT, Tamoxifen)Liver disease (early)Decreased
TBGAndrogens or anabolic steroidsLiver disease (late)Binding Site
CompetitionNSAIDsFurosemide IVAnticonvulsants (Phenytoin,
Carbamazepine)Hormone DegredationT4 is converted to T3 (active) by
5 deiodinaseT4 can be converted to rT3 (inactive) by 5 deiodinaseT3
is converted to rT2 (inactive)by 5 deiodinaserT3 is inactive but
measured by serum tests
Fisology Kelenjar ThyroidEfek kerja :Merangsang pertumbuhan anak
dg cara meningkatkan sintesa proteinMeningkatkan uptake 9transpor)
glukosa oleh sel :Meningkatkan glukolisisMeningkatkan
glukoneogenesisMeningkatkan absorbsi GHMeningkatkan sekresi insulin
Meningkatkan kaytabolisme lemak (pengosongan lemak pada jar.
Adiposa, Oksidasi asam lemak, pemecahan glikogen liver.Efek SSP
:Menaikkan kecepatan cerebrasi (hantaran syaraf)
:KegelisahanPsyconcurikAnsietas, kekhawatiran, paranoid (pathologis
kejiwaan)Tremor otot polos ok : peningkatan aktifitas pusat2 medula
spinalis yg mengatur tonus otot .Kesulitan tidurKelelahan
Efek pada sistem Kardiovaskular ;Vasodilatasi (akibat efek
menaikkan metabolisme)Aliran darah meningkat Meningkatkan kekuatan
kontraksi Frekuensi denyut jantung meningkatTekanan diastole
menurun (pulses pressure)Cardiac out put meningkat 50% (tekanan
sistole meningkat 10%)Efek pada sistem pernafasan :Akibat
metabolisme meningkat CO2 meningkat, maka pernafasan cepat dan
dalam.
+_PanasDinginT3/T4 bebasSekresi TSHT3/T4 bebasSekresi TRH
Struktur TSH berbeda antar spesiesTSH : mamalia lain punya pengaruh
thd biologis manusiaHypertiroidi disebut juga
TiroksosikosisHiperthiroidisme dapat didefinisikan sebagai akibat
dari peningkatan sekresi hormon thyroid yang berlebihan, respon
jaringan perifer tubuh terhadap pengaruh metabolisme yang
diakibatkan pengaruh berlebihan dari hormon tersebut.Keadaan ini
dapat timbul spontanatau sebagai akibat pemberian tyroid hormon
berlebihan.Ada 2 jenis Hypertiroidi spontan :Penyakit GravesToxic
Nodular GoiterPada Graves diseases biasanya terjadi pada usia 30-40
tahun, sering ditemukan pada wanita dibandingkan pria, sering ada
kaitan dg bentuk2 kelainan kelenjar endokrin (endokrinopati &
autoimun) yaitu ; reaksi terhadap sel tubuh sendiri (tidak menerima
sel2 yang lain) yaitu terhadap sel-sel kelenjar tiroid seperti
penyakit glomerulus nefritis (Autoimun)
Hypertiroidi/tirotosikosis :Gelisah (kelainan kepribadian)Banyak
makan tapi BB turun (kurus)Tidak tahan panasTekanan nadi (pulses
pressure) tinggiTremor pd jari2 ketika direntangkanBMR meningkat 10
100%Arytmia, gagal jantung, Myopati (lemah otot)Kelenjar tiroid
membesar dan diffuse , hiperplasia sel2 thyroidBola mata mau keluar
atau menonjol (exophtalmus)Penyebab :Tumor jinak maupun ganas pd
thyroid glandTumor hypofise (paling sering) adalah penyakit Graves
(Exophtalmus goiter)Sekresi T3/T4 meningkat krn faktor inhibitor
menurun shg sekresi TSH meningkatPenyebab :Adanya antibody thd
reseptor TSH di kelenjar tyroid yg mampu merangsang reseptor TSH
sekaligus,Meningkatkan aktifitas adenylat siklase sel2
ThyroidEtiologyHyperthyroidism with high RIU - Graves disease -
Toxic adenoma - Toxic multinodular goiter - TSH- producing
pituitary adenoma - Hyperemesis gravidarum - Trophoblastic
disease20EtiologyHyperthyroidism with low RIU - Subacute
thyroiditis - Exogenous harmone intake - Ectopic ovarii -
Metastatic follicular thyroid CA - Radiation thyroiditis -
palpation thyroiditis - Amiodarone induced21Signs and Symptoms
Tremulousness or jitterinessExophthalmos Weight loss despite
excellent appetite hypermetabolic
stateInsomniaFatiguePalpitationsHeat
intoleranceSweatingDiarrheaDeterioration in handwritingMenstrual
irregularitiesMuscle weakness/wasting manifested as exercise
intolerance or difficulty climbing stairsEye symptoms, which may
include pain or diplopiaNervousnessTachycardiaGoiterElevated plasma
levels of thyroxin and/or triiodothyronine
How To Diagnose HyperthyroidismTSH expect this to be lowFree T4
expect to be highNuclear thyroid scintigraphy iodine 123 uptake and
scan expect iodine uptake to increasedAnti-thyroperoxidase antibody
levelsTSH-receptor stimulating autoantibody levels (TSI
levels)Signs and symptoms of hyperthyroidTSH levelLow TSHHigh TSH
(rare)Measure T4HighSecondary hyperthyroidismImage pituitary
gland24Low TSHMeasure Free T4 LevelNormalHighMeasure Free T3
LevelNormalHigh-Subclinical hyperthyroidism-Resolving
Hyperthyroidism -Medication-Pregnancy -New thyroid illnessT3
ToxicosisPrimary hyperthyroidismThyroid uptakeLowHighMeasure
thyroglobulindecreasedIncreased Exogenous ThyroiditisIodide
exposureExrtraglandular productionDIffuseNodularhormoneGraves
diseaseMultiple areasOne hot areaToxic multinodular goiterToxic
adenoma25
Exopthalamos in Graves DiseaseLid Lag in Graves DiseasePenyebab
lain :Adenoma Thyroid shg tjd Hypertiroidi atau gejala hypertiroidi
:Mudah teransangIntoleransi thd panasKelemahan ototBerkeringat
banyakBB menurunDiare
GravesAntibody : dihasilkan oleh sel2 lymfosit berupa IgG
(dikenal sbg Tyroid stimulating Immunoglobulin (TSI), ditemukan
hampir pd setiap penderita Graves, sejenis TSI adalah LAT (long
acting tyroid stimulating) menaikkan t3/t4Penyebab timbulnya
antibody hanya pada Graves tidak pada Adenoma (hormon thyroid
exophtalmusTyroid toksikosis : beban thd CVS yaitu thd COP
meningkat tapi tak mencukupi kebutuhan jaringan ok ; vasodilatasi
perifer yg terjadi , resistensi perifer menurun shg tjd High out
put failureTyroid toksikosis yg lama dan berat menimbulkan kelainan
pada liver Ok ; pengososngan glikogen liver (payah liver) akan
memperburuk tirotosikosis shg T3/T4 lambat diambil di darah shg
terjadi hyperkatabolisme lebih besar dari O2 dan nutrisi yg
disediakanOphtalmopati : kunci diagnosis GravesKimosis : iritasi
konjunctiva (merah)Eksophtalmus (proptosis) : penonjolan bola
mataPenonjolan kelopak mataEdema periorbitalRefraksi kelopak mata
atasOfthalmoplegia : kelumpuhan otot2 penggerak bola mataDermopati
: Penebalan kulit krn : infiltrasi lymfosit , mukopolisakarida,
hydrophilik dan metakromatikMekedemalokal : sering pd tempat2 yg
sering mendapat tekanan contoh ; pretibial 9berupa penebalan kulit
yg non tender 9ditekan tetep keras) dg infiltrasi merah kebiruan
spt kulit jeruk dan batas jelas dg kulit sehatAcropachy :
pembengkakan jaringan lunak dan perubahan tulang (dapat dilihat
dengan foto rontngent, terjadi pada ujung2 jari mirip jari tabuh
(clubbing finger)
Tanda tanda Klinis ophtalmopati pada GravesTanda dallymple :
retraksi kelopak mata bagian atas 9kesan mata membelalak)Tanda von
Gracfe : kelopak mata terlambat turun dibanding bola mataTanda
Joffroy : Kulit dahi tidak dapat mengkerut pada waktu kepala
sedikit menunduk dan mata disuruh melihat objek yg bergerak ke
atasTanda Moebius : kelemahan dalam akomodasi dan konvergensi
mataTanda rosen back : tremor kelopak mata waktu mata menutupTanda
Stel Weq : mata jarang berkedipPentalaksanaan Hypertiroidi :Obat
Antitiroid : propil tioracil dan Methymazol paling sedikit 1 th ;
kerja obat menghambat sintesa dan pelepasan tyroxinePembedahan :
thyroidektomi subtotal setelah diberi propil tiouracilPenambahan
yodium Radiokatif ; tx ini tidak boleh pada anak dan wanita hamil.
Biasanya komplikasi akibat hyperthyroidisme akan sembuh sendiri
setelah pengobatan hyperthyroid. Cara kerja dg menurunkan aktifitas
kerja kelenjar thyroid , side efeknya ; mengganggu sumsum tulang yg
sedang tumbuh dan menggangu pertumbuhan janin. KomplikSI YG TIMBUL
KARENA PENGOBATAN :KRISIS TIROIDPAYAH HATIDECOMPENSATIO CORDISDx
pasti dengan laboratorium dg memantau T3/T4 turun dimana ;Sekresi
80 ugr tyroksin/hari40 ugr triiodotironin /hariClinical Outcomes of
Inadequately treated HyperthyroidismThyrotoxicosis. A
life-threatening thyrotoxic crisis (ie, thyroid storm) can occur:
fever, tachycardia, neurologic abnormalities, and hypertension,
followed by hypotension and shock. It can be Fatal.
Thyroid storm occurs in patients who have unrecognized or
inadequately treated thyrotoxicosis and a superimposed
precipitating event such as thyroid surgery, nonthyroidal surgery,
infection, or trauma.
Initially the acute mortality rate was nearly 100%. In current
practice, with aggressive therapy and early recognition of the
syndrome, the mortality rate is approximately 20%.
Severe Weight loss with catabolism of bone and muscle. Cardiac
complications and psychocognitive complications
Osteoporosis in men and women. The effect can be particularly
devastating in women, in whom the disease may compound the bone
loss secondary to chronic anovulation or menopause. Bone loss is
accelerated in patients with hyperthyroidismClinical Outcomes of
Inadequately treated HyperthyroidismSarcopenia and Myopathy
Neonatal hyperthyroidism
Apathetic hyperthyroidism - the only presenting features may be
unexplained weight loss or cardiac symptoms such as atrial
fibrillation and congestive heart failure.
Cardiac hypertrophy has been reported in thyrotoxicosis of
different etiologies.
Severe acropachy can be disabling and can lead to total loss of
hand function - clubbing of fingers with osteoarthropathy,
including periosteal new bone formation, may occur
Ophthalmopathy - compromised vision and blindness. Visual loss
due to corneal lesions or optic nerve compression can be seen.
