PEMICU IIDian Sri Utami405100286
ANATOMI
GLANDULA TIROIDTerdapat dibagian bawah leher ikut bergerak ketika menelanBentuk seperti kupu-kupu, terdiri atas 2 lobus yang dihubungkan oleh isthmus yang menyilang digaris tengah setinggi cincin cartilage tracea 2,3,4. Lebih kurang 40% akan terdapat lobus piramidalis, muncul dari bagian permukaan atas isthmus, yang lebih sering dari bagian kiri garis tengah. Bagian atas dari lobus piramidalis dapat berupa fibromuscular : Levator Glandula tiroid yang menuju ke os hyoid. Pada kasus dimana lobus piramidalis tidak ada, pita fibromuscular ini terdapat di bagian atas isthmus.
Glandula thyroid merupakan organ yang sangat vascularDibungkus oleh : Fascia Pretrachealis yang melekatkan organ ini pada larynx dan tracheaFascia ini ikut membentuk dan membatasi pembagian lobus-lobusnya. Setiap lobus berbentuk buah advokat dengan puncaknya mengarah ke atas sampai ke linea oblig cartilagenis trachea. Basisnya terdapat di bawah, setinggi cincin trachea ke 4 5.
Alat-alat disekitarnya Anterolateral : m. sternothyroidventer superior m. omohyooideusm. sternohyoideustepi anterior m. sternocleidomastoideus
Alat-alat disekitarnyaPosterolateral :A.carotis communisV. jugularis internaN. vagus
Alat-alat disekitarnyaMedial :Larynx-tracheam. constrictor pharyngis inferiorOesophagusantara oesophagus dan trachea terdapat N.Laryngeus recurrens Posterior :Glandula parathyroid superior dan anteriorAnastomose antara A. thyroidea superior dan inferior
PerdarahanA. Thyroidea superiorcabang A. carotis externaA. Thyroidea inferiorcabang truncus thyrocervicalisberjalan naik di belakang kelenjar sampai setinggi cartilage cricoidea, kemudian membelok ke medial bawah mencapai batas posterior kelenjar.N. laryngicus recurrens melintasi bagian depan atau bagian belakang arteri ini.A. Thyroidea ImaJika ada merupakan cabang A. Brachiocephalica atau arcus aortaBerjalan naik di depan trachea menuju isthmusBerasal dari :
Pembuluh balikV. Thyroidea superior : mencurahkan isinya ke vena jugularis internaV. thyroidea media : bermuara ke vena jugularis internaV. Thyroidea inferior : menampung darah dari isthmus dan polus bawah kelenjar, Vena ini dari kedua sisi akan beranastomose sewaktu berjalan turun ke bawah di depan trachea dan bermuara ke V. brachiocephalica
Pembuluh limfeLimfe akan dialirkan ke lateral, ke NnLl. Cervicalis profunda. Beberapa pembuluh menuju NnLl. Paratrachealis Pembuluh sarafDisarafi oleh serabut post ganglionik simpatis yang berasal dari ganglion cervicalis superior, media, dan inferior. Serabut-serabut ini mengikuti pinggir arteri, didistribusikan terutama pada pembuluh darah, hanya sedikit ke sel folikel. Beberapa serabut N. vagus juga mengikuti arteri ke kelenjar ini.
KELENJAR PARATHYROIDBentuk :Pipih, oval, ukuran 3 8 mm x 2 5 mm x 0,5 2 mm. Warna kuning kemerahan
Letak :permukaan posterior lobus lateralis glandula thyroid, biasanya berjumlah 4 buah.Kelenjar parathyroid superior : terletak di belakang pars superior glandula thyroidKelenjar parathyroid inferior : terletak di dekat tempat masuknya A. Thyroidea inferior, posisi dan jumlahnya bervariasi. Kelenjar parathyroid dapat tertanam pada kelenjar thyroid
Perdarahan :Cabang-cabang A. Thyroidea terutama dari A. Thyroidea inferior, juga dari anastomose cabang yang mendarahi m. prevertebralis, pharynx dan oesophagus.
Persarafan :Berasal dari sistim simpatis yang menyertai arteri, terbanyak berasal dari ganglion C6Pars inferior berhubungan erat dengan N. recurrens laryngeal
FISIOLOGI
Fisiologi Kelenjar TiroidKontrol Terhadap Kelenjar TiroidHipotalamusTRHPituitari anteriorTSHTiroidT3 T4__Gondok berkembang
TiroidTdk memenuhi penyedianan tiroksinTSHHiperplasi & hipertrofi
Fungsi Tiroid- Memacu metabolismeBerkaitan dengan suhu lingkungan- KalorigenesisStresACTH sumber Kalorigenesis Metabolisme Lemak & karbohidrat
-Hipertiroidisme- suhu tubuh tinggi, banyak berkeringat, penurunan bobot tubuh, iritabilitas, dan tekanan darah tinggi
- Hipotiroidisme- bobot tubuh meningkat, lamban dan tidak ada toleransi terhadap udara dingin pada waktu dewasa.-Perkembangan
ParatiroidBentuk pipih, oval / seperi buah pear, letak permukaan posterior lobus lateralis tiroid
Paratiroid, kalsitonin dan dihidroksikolekalsiferol merupakan hormon utama berkaitan dengan metabolisme seperti :KalsiumPirofosfatMagnesiumPengaturan metabolisme tulangDan komponen organik
Metabolisme Kalsium99% ion Ca++ berupa kristal mineral tulangKalsium memiliki 3 fungsi dalam sel- Komponen kunci dalam membran sel, permeabilitas serta sifat listriknya- Sebagai faktor perangkai selama ekksitasi dan kontraksi semua jenis otot.- Stadium awal untuk merangkai tanggapan sel sasaran terhadap hormon.
Kalsium diserap diusus dibantu oleh 1,25- Dihidroksikolekalsiferol metabolit Vit D3 diginjal yang dikontrol oleh paratiroid.
Biosintesis PTHPTH sapi, manusia dan babipolipeptida linier dengan BM 9500 dan 84 residu aaPTH disintesis sbg prapro-PTH (115 residu aa)Prapro-PTH masuk RE25 residu aa dikeluarkan dr terminal NPro-PTH (90 residu aa)Di aparatus golgi 6 residu aa dari terminal N dikeluarkan lagi PTH ( 84 residu aa)Kadar normal PTH dlm plasma ; 10-55 pg/mlWaktu paruh kurang dari 20 mntPolipeptida disekresikan akan diuraikan oleh sel-sel kuffer di hati mjd 2 polipeptidaFragmen terminal C yang tdk aktif BM 7000 dan fragmen terminal N yang aktif dgn BM 2500
HipoparatiroidismePengambilan tiroidkadar kalsium turunHipokalsemia hilang kemampuan mobilisasi kalsium oleh tulang, ginjal dan ususIon kalsiun turun pada ekstraselhiperiritabilitas neuromuskulertetani, kejang otot, kematianTransport kalsium usus turun 1,25-dihidroksikolekalsiferol tidak terbentuk krn PTH tidak ada
Hiperparatiroidisme Meningkatkan resropsi dan mobilisasi kalsium, shg kalsium plasma meningkat dan fosfat plasma menurunPTH meningkatkan ekskresi fosfat dalam urin ( reabsropsi fosfat ditubulus proksimal menurun dan reabsropsi ion kalsium meningkat ditubulus distal.Peningkatan reabsropsi kalsium oleh ususMenyebabkan kelumpuhan pada tulang karena tingginya deposisi kalsium sehingga menghilangkan mineral
KalsitoninRantai polipeptida td 32 residu aa , BM 3000 Dilepaskan jika kalsium serum tinggi Bekerja di tulang dan ginjal Penghambat reabsropsi Mencegah pelunakan tulang
Fungsi 1,25-DihidroksikolekalsiferolBereaksi seirama dgn PTH, mengontrol mineralisasi tulangMeningkatkan reabsropsi kalsium dan fosfat oleh tubuli ginjalMeningkatkan transport kalsium dan fosfat yang melintasi sel-sel mukosa usus.
BIOKIMIA
Thyroid RegulationSomatostatin, GlucocorticoidDopamine
Thyroid hormone synthesis1) Iodide pumpRate limiting step in thyroid hormone synthesis which needs energyFollicles have in their basement membrane an iodide trapping mechanism which pumps dietary I - into the cellNormal thyroid: serum iodine is 30-40:1Iodide uptake enhancers:TSHIodine deficiencyTSH receptors antibodyIodide uptake inhibitorsIodide ionDrugsDigoxinThiocynateperchlorate
Thyroid hormone synthesis2) Iodide oxidation to iodine and OrganificationInside the cells, iodide is oxidized by peroxidase system to more reactive iodineIodine immediately reacts with tyrosine residue on a thyroid glycoprotein called thyroglobulin to form :T1= mono-iodotyrosyl thyroglobulinT2= di-iodotyrosyl thyroglobulinBoth processes are catalyzed by thyroid peroxidase enzyme
Thyroid hormone synthesis3) CouplingT1& T2 couple together to form T3&T4MIT +DIT = T3 (Tri-iodothyronine)DIT + DIT = T4 (Thyroxin)All attached to thyroglobulin and stored in the colloid Thyroglobulin molecule This process is stimulated by TSH
Production of Thyroid HormonesNIS (Na+/I- Sympoter)TPO
Effects of thyroid hormonesFetal brain & skeletal maturationIncrease in basal metabolic rateInotropic & chronotropic effects on heartIncreases sensitivity to catecholaminesStimulates gut motilityIncrease bone turnoverIncrease in serum glucose, decrease in serum cholesterolConversion of carotene to vitamin APlay role in thermal regulation
Increase BMR ( Basal Metabolic Rate )cellular metabolic activity by : size, total membrane surface & number of mitochondria ATP formation active transport of ions ( Na+, K+ )
Promote growth & development of the brain during fetal life and for the first few years of postnatal life
Carbohydrate metabolism enhanced glycolysis, gluconeogenesis, GI absorption & insulin secretion Fat metabolism enhanced fat metabolism Accelerates the oxidation of free fatty acids by the cells plasma cholesterol, phospholipids & triglycerides Body weight the appetite, food intake, GI motility but the body weight
Cardiovascular systemvasodilatation blood flow cardiac output heart rateRespiratory the rate and depth respirationCNS extreme nervous & psychoneurotic tendencyMuscle make the muscles react with vigor -----> muscle tremor ( 10-15 times/sec ) Sleep: extreme fatigue but is difficult to sleep
KELAINAN TIROID
Causes , Clinical Features & Consequences of HypothyroidismCongenital HypothyroidismAcquired Hypothyroidism
EtiologyCongenital Acquired
Primary SecondaryTertiary
Congenital HypothyroidismOccurs in about 1/4000 live birthThyroxin is important for CNS development and postnatal growthThe most frequent cause is congenital absence of the thyroid gland (athyrosis)Presentations may include cyanosis, prolonged hyperbilirubinemia, poor feeding, hoarse cry, umbilical hernia, respiratory distress, macroglossia, large fontanelle, and delayed skeletal maturationRarely, neonatal hypothyroidism is transient
Congenital HypothyroidismEtiology1) Thyroid dysgenesis Idiopathic: Commonest cause in 95% of casesAthyreosis (40%)Hypoplasia (40%)Ectopia (base of tongue, midline) (20%)
2) Thyroid dyshormonogenesis (A.R) (10%)
3) Hypothalamic-pituitary hypothyroidismAnencephaly, holoprosencephaly, S.O.Didiopathic
Congenital Hypothyroidism4) Transient hypothyroidismMaternal TRABMaternal ingestion of goitrogen5) Drugs 6) Iodine excess7) Iodine deficiency
Anti-thyroid Drugs and fetusThionamides PTU & MZTIodideLithiumAmiodaroneRadioiodine After 10-12 wk gestation can damage fetal thyroid gland
Presentations of congenital hypothyroidismMacroglosiaProlonged hyperbilirubinemiaPoor feeding Hoarse cryDecreased activityConstipation Umbilical hernia Dry yellow skinlarge fontanelle Delayed skeletal maturation
Neonatal screening for congenital hypothyroidismRoutine in most countries worldwideFilter paper blood spot measuring TSHWhy ??Clinical manifestations at birth, usually are subtle or even absent (passive transplacental maternal thyroxin)At birth, surge of TSH (stress of delivery) up to 30 -40 u/mlEarly detection will prevent mental retardation or decreasing IQ of affected neonatesThyroxin is important for CNS development from birth till 3 years of lifeScreening program will miss 2ry/ tertiary casesThe program is hampered by a high rate of false positive results
Acquired HypothyroidismMore common than hyperthyroidism99% is primary (< 1% due to TSH deficiency)Hashimotosmost common thyroid problem (4% of population) most common cause in iodine-replete areaschronic lymphocytic thyroiditisAssociated with TPO antibodies (90%), less commonly Tg antibodiesIatrogenic Hypothyroidism from radioactive iodine therapy
Acquired HypothyroidismSubacute thyroiditisPainful, often radiates to the earc/o malaise, pharyngitis, fatigue, fever, neck pain/swellingViral etiology (URI/ pharyngitis)self-limited. Can tx inflammation w/ ASA, NSAIDs or steroids Suppurative/ Acute Infectious thyroiditisInfections of the thyroid are rare normally protected from infection by its thick capsuleBacterial >> fungal, mycobacterial or parasiticPts are acutely ill w/ a painful thyroid gland assoc w/ fever/chills, anterior neck pain/swelling, dysphagia and dysphonia
Acquired HypothyroidismSymptomsGeneral Slowing DownLethargy/somnolenceDepressionModest Weight GainCold IntoleranceHoarsenessDry skinConstipation ( peristaltic activity)General Aches/Pains Arthralgias or myalgias (worsened by cold temps)Brittle HairMenstrual irregularitiesExcessive bleedingFailure of ovulation Libido
Acquired HypothyroidismExaminationDry, pale, course skin with yellowish tingePeriorbital edemaPuffy face and extremitiesSinus BradycardiaDiastolic HTN Body temperature Delayed relaxation of reflexesMegacolon ( peristaltic activity)Pericardial/ pleural effusionsCongestive heart failureNon-pitting edemaHoarse voiceMyopathy
GoiterA swollen thyroid glandAssessment;how big, how quickly has it developed, is it smooth or nodular, is it painful, any associated lymph nodes, any sudden changes, is it big enough to cause local symptoms (e.g. breathing problems)
Myxedema
Hypothyroidism --- loss of scalp hairA Color Atlas of Endocrinology p70
Hypothyroidism with short stature
Diagnosis
Congenital hypothyroidismThyroid hormone levelTSHThyroid scan Acquired HypothyroidismTSH fT4 Thyroid antibodiesThyroid ultrasoundTSH: low in secondary hypothyroidism high in primary hypothyroidismTRH test: to differentiate between secondary & Tertiary hypothyroidism
Euthyroid sick syndromeAbnormalities in thyroid function tests observed with systemic non thyroidal illness Cytokine mediatedReduced TRH release, TSH response, T4 production/release, T4 to T3 conversion and TBG productionIncreased somatostatin secretionInhibitory effects of dopamine and glucocorticoid on TRH actionVery low T4 values have a poor prognosis
Treatment
L-thyroxin replacement should be started as soon as possibleIf treatment is delayed > 2 months of life, > 75% risk of hypothyroidismOn the other hand, delayed treatment of hyperthyroidism will lead to advanced skeletal maturation, craniosynostosis and intellectual deficitsL-Thyroxin is the main drug for treatment of hypothyroidism, whatever is the cause
Treatment
Age L-Thyroxin doseTotal dose (g/day)L-Thyroxin dose g/ kg/day
0-66-121-56-12>12 25-50 50-75 75-100 100-150 150-200 8-10 6-8 5-6 4-5 2-3
Causes , Clinical Features & Consequences of Hyperthyroidism
Hyperthyroidism (Thyrotoxicosis)DefinitionExcessive secretion of T3 & T4Affects metabolic processes in all body organsHyperthyroidism is 4-10 times more prevalent in womenMost common endocrine disease second only to diabetes as the most occurring endocrine disease
ThyrotoxicosisCauses
Transient Neonatal thyrotoxicosisInfectious : Acute & subacute thyroiditisDrug induced: Amiodarone, interferon &interleukinIatrogenic
Thyrotoxicosis Causes
Persistent Graves diseaseToxic multinodular goiterToxic solitary adenomaCentral (pituitary origin)
Neonatal ThyrotoxicosisOnly occur with 5% of thyrotoxic mothersSeverity consistent in future pregnancies20% mortality if untreatedEvolves rapidly, evident by day 7 of life, unless TRAB blocking antibody is presentAssociate with cranial synostosis and learning difficulties, if not treatedFetal thyrotoxicosis in rats leads to abnormal CNS myelinationParents should be aware of potential learning problems (early school years should be monitored)
Neonatal hyperthyroidism born to mother with Graves diseaseA Color Atlas of Endocrinology p51
Graves diseasePathogenesisT-cell dependent autoimmune disease60% have HLA association with A1, B8, DR3,DR4,DR5Autoimmune disorder that results in production of antibodies directed against thyroid antigens: TSH receptors Thyroglobulin Thyroid peroxidase
Subacute ThyroiditisClinical course lasts weeks to monthsAcute phase (2-6/52) with clinical and biochemical hyperthyroidismRecovery phase (weeks-months) transient hypothyroidism then euthyroidismClinically, history of sore throat, fever, tender goiter, cervical lymphadenopathyHigh ESR, negative antibodies and absent radioactive I131 uptake
HyperthyroidismMay result in significant morbidity, mortality & even deathSymptomsJittery, shaky, nervousDifficulty concentratingEmotional labilityInsomniaRapid HR, palpitations, Feeling HotWeight LossDiarrheaFatigueMenses : lighter flow, shorter duration
ThyrotoxicosisHeart: Increased heart rate, contractility and cardiac outputSkeletal muscles: Proximal myopathy, easy fatigability and muscle atrophyGonads: Irregular menstrual cycles, impotenceLiver: Low cholesterol LDL & apolipoproteinBone: Increased bone turnover, osteoporosis & increased risk of fracture
Grave's ophthalmopathyThe pathogenesis of infiltrative ophthalmopathy is poorly understood It may occur before the onset of hyperthyroidism or as late as 15 to 20 yearsThe clinical course of ophthalmopathy is independent of the clinical course of hyperthyroidismInfiltrative ophthalmopathy may result from immunoglobulins directed to specific antigens in the extraocular muscles & orbital fibroblastsThe antibodies are distinct from those initiating Graves'-type hyperthyroidism
Hyperthyroid Eye DiseaseHyperthyroidism (any cause)Lid lag, lid retraction and stare Due to increased adrenergic tone stimulating the levator palpebral muscles.
True Graves OphthalmopathyProptosisDiplopiaInflammatory changesConjunctival injectionPeriorbital edemaChemosisDue to thyroid autoAbs that cross-react w/ Ags in fibroblasts, adipo-cytes, + myocytes behind the eyes.
Graves ophthalmopathy
Hyperthyroid Eye Disease
Graves DermopathyThyroid Dermopathy Thickening and redness of the dermisDue to lymphocytic infiltration
Thyroid AcropachyThyroid acropachy. This is most marked in the index fingers and thumbs
Tremor of the handA Color Atlas of Endocrinology p49
DiagnosisTSH level usually < 0.05 u / ml95 % of cases, high FT4 & FT3In 5% high FT3 with normal T4 (T3 Thyrotoxicosis)Thyroid receptor (TRAB) are usually elevated at diagnosisAntibodies against thyroglobulin, peroxidase or both are present in the majority of patients
Thyrotoxicosis- TreatmentThree modalities for more than last 50 yearsRadioactive iodine,antithyroid drugs&surgery None is optimalNone interrupts the autoimmune processEach has a drawbacksThere is no treatment for underlying causeNo other research options so far
Neonatal ThyrotoxicosisTreatment 1) Lugols iodine 1 drop tid for 1-2 / 7Dramatic coarse therapyBlocks T4 release, synthesis and I uptake (Wolf Chaikoff effect)2) Propranolol3) Carbimazole will take several days to have an effect on T4 synthesis
Hyperthyroidism (Treatment)1) -blockers (symptom control)Propranolol (Inderal )Atenolol (Tenormin )Metoprolol (Lopressor )
2) 131-RAIA (70% thyroidologists prefer)DosingGraves: 10-15 mCiToxic MNG/Adenoma: 20-30 mCi Absolute contraindicationsPregnancy and lactation (excreted in breast milk)!Pregnancy should be deferred for at least 6 months following therapy with radio-active 131It is advisable to avoid 131-Rdio-active iodine therapy in patients with active moderate severe Graves ophthalmopathy.
Hyperthyroidism (Treatment)3) Antithyroid Drugs (30% thyroidologists prefer)Propylthiouracil (PTU) 100 mg bid-tid to startMethimazole10X more potent the PTU 10 mg bid-tid to startComplications of ATDs Agranulocytosis (1/200-500)usually presents w/ acute pharyngitis/ tonsilitis or pneumonia. Rash Hepatic necrosis, Cholestatic jaundice Arthralgia
Hyperthyroidism (Treatment)4) Surgery (sub-total thyroidectomy)IndicationsPatient preferenceLarge or symptomatic goitersWhen there is question of malignancyNeed to be euthyroid prior to surgery To the risk of arrhythmias during induction of anesthesiaTo the risk of thyroid storm post operativelyATDs + -blockersRisksPermanent hypoparathyroidismRecurrent laryngeal nerve problemsPermanent hypothyroidism
=DIFUS NON TOXIC GOITER=ENDEMIC GOITER
TIROIDITISAKUT ( SUPURATIF ) Disebut juga infective thyroiditis, infeksi oleh bakteri / jamur. Contoh kuman : pneumococcus, streptococcus hemolyticus, dll. Gejala Klinis : nyeri dileher mendadak, malaise, demam, menggigil dan takikardi. Pemeriksaan Lab : leukositosis, LED meningkat, sidikan tiroid menunjukkan nodul dingin. Pengobatan : utama :antibiotikkokus gram + : penisilin, tetrasiklin.jika ada abses : lobektomi.
SUB AKUT Umumnya diduga karena virus MK : pasien mengeluh dileher bagian depan menjalar ke telinga, demam, malaise. Pem.fisik : tiroid membesar, nyeri tekan,takikardi berkeringat, tremor, dll Pem. Lab : leukositosis, LED meningkat, pada 2/3 kasus hormon tiroid meninggi. Pengobatan : biasanya sembuh sendiri sehingga pengobatan yang diberikan simptomatis.- asetosal untk mengurangi nyeri- pada keadaan berat : glukokortikoid
ETIOLOGI DAN PATOGENESISa. Sintesis hormon tiroid yg tganggu, misal krn def.yodium, masukan goitrogen dr mknan atau defek pd jalur biosintetik hormon.b. Yodinisasi yg tidak sempurna dr tiroglobulinc. Antibodi yg menstimulasi pertumbuhan tiroid
PATOLOGI- pd stadium awal, kelenjar mmperlihatkan hipertropi seragam, hiperplasia, dan hipervaskularisasi- sebagian kelenjar mmperlihatkan involusi atau hiperinvolusi yg seragam dg akumulasi koloid
MANIFESTASI KLINIS- pembesaran tiroid- muka sembab, pusing, dan sinkop (tanda Pemberton)- suara parau
DIAGNOSIS- T4 dan T3 serum mendekati batas normal- RAI normal namun mungkin dpt meningkat pd def.yodium atau defek biiosintesis
TATA LAKSANA- untuk mengurangi ukuran struma bs dg menyediakan hormon eksogen dlm jumlah cukup untuk menghambat sekresi TSH- pemberian hormon tiroid: Levotiroksin dg dose: 100 g stp hari dan dosis ditingkatkan bulan berikutnya sampai maksimal 150 atau 200 g/hari.