SISTIM ENDOKRIN

SISTIM ENDOKRINDr. Hj. RESMI KARTINI, MS

Homeostasis seluler diatur :Sistim saraf Sistim endokrin terutama hipotalamus ( pituitari )Dan sel neuroendokrin APUD

HormonKelenjar endokrin target organinteraksi melalui reseptor

Reseptor - reseptorSurface membrane receptorsHormon polipeptide ( pituitary )KatekolaminCytoplasmic reseptorSteroidNukleusIntranuclear reseptorThyroid hormonSitoplasma

HIPOTALAMUS

KONTROL

KELENJAR ENDOKRIN PERIFERFEED BACK MECHANISMPITUITARY HORMON STIMULATORY INHIBITORY

Pituitary gland

ANT:adenohipofisis Rathkes PouchPost : Neuro Hipofisis Floor Ventr IIIPost - Vasopresin ( ADH ) -OxytocinAnt -Asidofil somatrroph GH mammotroph PrL -Basofil Corticotroph Proopiomesamocortin acth,msh, endorfin,lipotropin Tirotrof TSH Glikoprotein Gonadotrop: FSH,LH -Khromofob

PATOLOGIPrimer : Lobus Ant PostAdenohipofisis Hiper / Hipopituit 1.Tropic hormon / Hipopituitary : 75 % destruksi -tumor non fungsional -Infeksi -Hipotal (jarang)

2.Local effect - rare - Sela tursika besar --- Xray,CT,MRI Expansile lesion ( neoplasma )

- Defek Expanding dis.pit Chiasma opt / N. II Bitemporal hemianopsia visual impairment- Sangat jarang Tek intrakranial( Headache, nausea, vomitus Neoplasma )

HiperpituitariAdenomaKarsinoma (Hipotalamus Stimulasi >> Pituiti)----- jarangAdenoma MonoclonalSingle hormon Manifestasi klinikPlurihormonalPrimitif / Pluri potent cells

Morfologi

Mikro adenoma ( < 10 mm )Mikro adenoma ( > 10 mm )Mikro adenoma : 40 % unselected autopsi. single ,multipel multiple foci hiperplMakro adenoma : Ekpansi dpt erosi tulangSella enkapsul poorly diliputi retikulin chiasma optikum syaraf kranialDasar otak,sinus cavernosus, tlg sfenoid

Mikroskopis :

Uniform sel poligonal tersusun sheet,cord,nests.Stroma vascularisasi bertambahNecrosis ischemik,psammoma bodiesHemoragik pituit apoplexyMitosis /pleomorfik ? Malignancy metastasis

PITUITARY ADENOMA

PITUITARY ADENOMA

Somatotropic ADENOMASSomatotro. acidophilic macro adenoma GH Akromegali Gigantisme jarangHiperplasiaAkromegali Adult Megali :akral,Kepala, tgn, Kaki,jaw,lidah Soft tissue

Gigantisme : ChildrenSel matur uniform --- granulatedSebagian pleomorfik asidofil1/3 BSM Prl bimorfusPrl granul pada sel neoplastik tidak terdapat pada darah

ProlactinomasSparsely granulatedHiperplasia jarangHiperprolactinemi lesi hipotal drug impair dopaminergic trans mission (metildopa,reserpin) estrogen terapi Hipogonad laki 2 --- impoten,infertil peremp --- galactorrhea amenorrhea

2/3 macro adenoma granulated acidophilic cells1/3 Micro adenomaKalsifikasiSel uniform sela tursika

Corticotroph tumors

basophilik mikroadenoma ACTH ------ Hipersekresi kortisol adrenalHiperplasia / multiple micro adenoma cushings diseasePro opio melanocortincrookes hyaline changeskhromofobic less well defined cortisol excessSilent tumor besar induce local changes

Other functioning AdenomasGonadotroph tumor 6%Laki 2 FSH LH hipogonadPerempuan Gonadotropin sekresi - wl pun LH dapat dideteksi serum BesarMikros : Laki-laki Pleom, wanita :uniform small cell

CARCINOMA

DiferensiasiDiagnosis Matastase : KGB Bone Hati dll

Disorders associated with HypopituitarismGerm cell TKraniofaringiomaGliomaKetiga diatas lesions of hypothal,ant hipofis hipopituitary 75 % destruksi klinikTumor klinik : Diab-insipidus Growth Acceleration Delayed puberty

90% hipopituitproses destruksi adeno hipophisisTU: Nonsecretory adenomas Sheehans pit.necrosis Empty sella tursikaNeoplasma .metas.Pituit apopleksi chemorDisruption blood supply by sistemic arteritis / or trSinus venosus cavernosusDistruksi inflamasi lob ant by sarcoidosis / inf,surgical / radiation ablation metab.dis

NON SECRETORY CHROMOPHOBE PITUIT ADENOMA

25 -30 %Klinik efek lokal - Kelainan lapangan pandangan - Sakit kepala - hipotensi --- one of target endoc organ UNDER pituit control ( HIPOTIROID HIPOGONADISM )

MORFOLOGIBesar silent bertahun-tahunNull cell adenomaOncocytoma sparsely granules lessionImunohistokimia FSH, / hormon, LH

SHEEHANS SYNDROME / NECROSIS PITUIT POST PARTUMHamil pituitary besar Hemorr vasospasmenekrosis.iskemik/ infark lobus anterior Shock

DICSickle cell anemiaTr. Sinus cavernosus arteritis temporal, traumatic injury pembuluh darah, DM (lama)

95-99 % destruksi lobus anterior defisiensi gonadotropic laktasi menurun (puerperium)Defisiensi TSH atau hipotiroidACTH (insufisiensi adrenocortical)Infark : soft, pale fibrosis

EMPTY SELLA SYNDROMEHernia arachnoid deffect diafragma sellaTekanan CSF atropi pituitary empty sella

SINDROMA PITUITARY ANTERIORJarangTerutama lesi hipotalamus suprasellerDisfungsi ADH defisiensi diabets insipidusArginin vasopresin:oksitosin kontraksi uterus partus stim glandula lactating

Neoplastik : tumor supraseller, metas Ca, abses, meningitis, TBC, sarcoidosis (inflamasi hipotalamus-hipofisial)Surgical radiasi hipotalamus-hipofisialSevere head injuryIdiopatik

Hypothalamik suprasellar tumors Neoplasma jrg GLIOMA / Craniopharyngioma

Hipofungsipituitary anteriorHiperfungsiDiabetes insipidusCraniopharyngiomaDari sisa rathkes pouchPada sella, suprasellar Anak, dewasa mudabenign

MORFOLOGI3-4 cm, solid encapsule, kistik multilokuler, kalsifikasiMikroskopis :

ADENO HIPOFISIAL HIPOFUNGSILorain levi syndromeGH / hormon lain HipoglikemiagonadotropinKraniofaringiomaFrohlichs syndromeObesitasPerkembangan sex arrestMental sub normal,Growthtumor

Prepubertas--- growth pituitary dwarfism sexual retard

HIPOGONADISMAmenoreLoss of axilla and pubicSterillityOvarium atropi, genital atropiTestis atropi, sterillityLoss of axilla, pubicHipotiroid TSHHipoadrenal ACTHPanhipopituit Simmonds

TSHIodine in diet iodine+tirosin T3 sekresi abs stimulasi monoiodo oleh TSH oleh TSH andbowel diiodotirosinT4 blood

TIROIDTirotoksikosis (hipertiroidism)HipotiroidismDifus / fokal enlargement (Goiter) tidak ada hubungan antara lesi morfol dan klinik

TIROTOKSIKOSISHipertiroidism, Free T3 , T4 Hiperfungsi tiroid (Graves disease) hipertiroidismNon hiperaktif kelenjar tirotoksikosisSindrom :NervousnessBB (nafsu makan baik)PalpitasiHeat intoleranceRapid pulseWarm skinFatigabilityEmosi labilKelemahan ototPerubahan haidBMRTremor tanganPerubahan mataKelenjar tiroid membesar

MORFOLOGIVasodilatasi : Periferheat lossSirkulasi hiperdinamik general kulit : warm, moist, flushedhipertiroidperubahan mataGraves disease---proptosis perubahan imunologiInflamasi sekunder jaringan retroorbital jantung TakhikardiPalpitasiKardiomegaliAritmia, fibrilasi supraventrikuler

GRAVES DISEASE

THYROTOXIC CARDIOMIOPATHYFokus infiltrasi limfosit, eosinofil, interstisial, fibrosis ringan, fatty changesManifestasi lain: Otot skelet : atropi, fatty infiltrasi, infiltrasi limfosit fokal Hati : minimal fatty changes, fibrosis periportal, infiltrasi limfositOsteoporosis general lymphoid hyperplasia dg lymphadenopathy

Graves Disease< 40 th (85%)HipertiroidDiffuse toxic hyperplasiaHiperfungsi tiroid Pemberian iodine >> pada kelainan (T3 / T4)tiroid Jod basedows disease

HIPERFUNGSI TIROIDT3 T4 sirkulasi tirotoksikosisTerdiri dari :Graves diseaseToxic adenomaToxic noduler goiterKlinik :ExophtalmusProminent tiroidBMR Skin warm, sweaty : heat intoleranceWeakness,hiperkinesia, emotional instabilityBBGlucose tolerance, glukosuriaNadi , Cardial arrhythmia and failure ( orang tua )TSH

TIROIDITISTiroiditis interstitialPalpation tiroidSuperior / inferior tiroidjarang direct traumaticImunologi Staf, strep, salmonella, enterobacter, M tbc, jamur (candida, asper, mucor)

MorfologiKelenjar besarHasimotoSub acute granulomatous tiroiditisSub acute limfositic tiroiditisRiedel struma

HASHIMOTOS THYROIDITIS/ STRUMA LYMPHOMATOSA/ LYMPHADENOID GOITER : Goitrous hipotirNon endemic goter (children)Autoimun diseaseBerlangsung lama hipotiroid hipertiroidhashitoxicosisHashimoto Grave

ETIOLOGIAutoimunDefek fungsi tiroid spesifikSupressor T cellAntibodies tiroid peroksidase (antimicrosomal antibodies)AB Spesifik untuk tiroglobulinTSH reseptor

MorfologiKelenjar besar, diffuse, asimetris, kapsul intak, coklat noduler, Rubbery tissueMikroskopis :Perjalanan penyakit : usia pertengahanHipotiroidismAtropiStadium dini metabolisme normal, fungsi tiroid, TSH, T3 T4 Prognosa baik: 1-200 lymphomaGoitrous hipotirNon endemic goter (children)Autoimun disease lymphoma

HASHIMOTOS THYROIDITIS

HASHIMOTOS THYROIDITIS

Riedels fibrous thyroiditis /Riedel strumaCausa unknownAtropi/hipertropi, fibrosis,firm,abu 2 caKadang : Retroperitoneal fibrosis( multi fokal fibro sclerosis )Mikros : fibrosis , infiltrasi limposit scant,fol tiroid distorsi

Sub acuta granulomatous(de QuervainS )Thyroiditisde Quervains Thy Self limited, inf granule / Giant cell / Gran.thy dekade 2-5 : --- 3: 1Unknown virus onset didahului infeksi virus (mumps,measles,influ,adeno vi,coksackie vi,echo vi) Klinik : demam,tir >>> nyeriMORFOLOGI :Tir > > > /

MORFOLOGI

Tir > > / Fokal asimetrisOpt gland tkena irreg : lokalisasi firm,kuning putih ruberryHistologi :Patchy LamaProses inflam,micro absesLanjut folikel rusak / agregat sel sukar ? sel dari folikel makropagmultinuclear giant cell (koloid) fibrosis gran thyroiditis

SUB ACUTE GRANULOMATOUS THYROIDITIS (DE QUERVAINS THYROIDITIS)

SUBACUTE LYMPHOCYTIC (PAINLESS) THYROIDITIS? GOITROUS HYPERTHYROIDFokus infiltrasi limfositJaringan fibrous interstisialKel tir >> dan Hipertiroid Amerika utara 15 % graveGoitrous >> tdk terdeteksi self limiting disease hipotiroid? T3 dan T4

GRAVES DISEASEHipertiroid hiperfungsi difuse hiperplasia goiterInfiltratif ophtalmopathy, dermopathyOpthalmopathy :Lid lagUpper lid retractionEdem periorbitalStareOtot mata lemahproptosisDermopathy:Edem pinggung kaki, tungkaiPlaque like / nodulerLokal myxedema(-) Tirotoksikosis diffuse toxic goiterUSA 12-20 %

ETIOLOGI DAN PATOGENESISAUTOIMUNIg G antibodi TSH reseptorThyroid stimulating AB (TSAb)Thyroid stimulating Ig (TSI) HashimotoPada pdrt Graves dpt an.pernisiosa, rheumatoid arthritisMORFOLOGI :Diffuse hyperplasia80-90 grKapsul intactDiameter parenkim lunak daging

HISTOLOGICell>> vask Pseudopapil mushroom, folikelKoloid , pucatStroma jaringan limfoid >>, folikel >>general lymphoid hypertrophyPERJALANAN PENYAKIT Muda tirotoksikosis tir > simetrisUptake JOD131 Proptosis >> injury cornea, ulserasi, mata (-)

DIFFUSE AND MULTINODULAR GOITERKerusakan output hipertiroid kompensasi kad TSH Hipertropi, hiperplasia epitel folikel Diffuse/ multi nodulerTir > hor < eutiroid1. diffuse non toxic (simple goiter)2. multinod goiter

Diffuse non toxic (simple) goiterPembesaran diffuseHiper/hipofungsiENDEMIC GOITERSimple goiter, lokalisasi geografik 10 % populasi pegununganIntake yod hor tir TSH hipertir, hiperplasiaCa, flour goiterMakanan dan sayur

NON ENDEMIC / SPORADIC SIMPLE GOITER 8 : 1Pubertas / Dws mudaTSH Kehamilan estrogen TBG 1. defek transport jod T3 T42. defek organifikasi feed back inhibition TSH3.defek dehalogenaseDefek iodotirosin coupling

Multi noduler goitersimple goiter multi nod goitersporadik endemiknon toxictirotoxicosis (toxic multi nod goiter) plummers diseaseJarang hipotiroidTiroid membesar DD/neoplastikOlder ok. komplikasi Sel tiroid normal-heterogen perbedaan potensiProliferatifFolikel membesar ruptur hemoragik jar. Parut kalsifikasi

Morfologi1. nod hiperplasi folikel, folikel dg koloid banyak2. irreguler scarring3. Hemoragik fokal, deposit hemosiderin4. kalsifikasi fokal pd jar. Parut5. mikrokista

Perjalanan PenyakitKlinik penting:Ukuran, lokalisasi massaFungsi abnormal biasa : tirotoksikosisPerbedaan dg neoplasmaCVS pd org tua: fibrilasi atrium, takikardi, heart failure kosmetik, disfagi, stridor inspirasi, penekanan v,kava sup : distensi vena leher dan ekstremitas atas, edem palpebra / konjungtiva, batuk dan sinkope

Hemoragik tiroid >>, nyeri dan serakHiperfungsi toksik noduler goiterUptake jod 131 , T3 T4 Akumulasi radioaktif tersebar ke dalam tiroidJarang menyebabkan noduler hiperfungsiTiroid >> 2000gr 1 atau lebih lobus menekan trakea, Oesofagus, dan dibelakang sternum intrathoracic plunging goiter

MorfologiMultinod heterogenNod batad tidak tegasJar. Parut tampak sebagian encapsul Penamaan yg salah adenomatous goiter dan multiple coloid adenomatous goiterDD/: neoplasma sukarCT scanUSGMRIBiopsi aspirasiResiko Ca namun data (-)

NODULER GOITER

NODULER GOITER

HipotiroidismHipometabolismeHipotiroid1. selama fase perkembangan, invasi, kretinisme physical, mental retard2. older children/adult myxedemaAkumulasi hidrofilik mukopolisakaridPada jar penyokong edem dan kulit tebal

KausaUSA hipotiroid, idiopatik primertiroiditis autoimun atropik15-60% Sustansi ------------TSH reseptor bloking auto ABdapat menghilang spontanTerapiPost tiroidektomi >>

CretinismJarangRetardasi fisik dan intelektualPada saat lahir tergantung dr hormonal efeknya terlihat setelah bbrp minggu-bulan2Klinik : kulit kering,kasar Widely set eyes peri orbital bengkak hidung lebar,flattened lidah besarJod -pada perkembangan fetal Agenesis tiroid Defek biosintese kongenital Pertumbuhan skelet terganggu, perkembangan otak Endemik cretinism endemik goiterSporadic cretinism cretinism sporadik atropi

MYXEDEMAOlder child diantara kretin dan dewasa dg hipotiroidAdult pelan2 Aktifitas fisik dan mental lambatBicara, intelek Edem preorbitaKulit tebal, kasar, kering, lidah >>Facial feature thikenedLetargik keringat banyak, konstipasi, fungsi motorik => Sebagai kretinMikros : miofiber edem, striae hilang

TUMORSNODUSA, adult, 2-4%, nod daerah endemik goiter,90%adenoma, karsinoma 25-35kasus/milionSolitary mass nodules, multinucleated goiter, kista, pembesaran asimetrisNod soliter neoplastikwarm/hot nodul benignaPenderita> non neoplastik

ADENOMADari epitel folikel ad. FolikulerMikros : fetal,embrional,simple, colloid, mikro & makrofolMorfologi :DD/ sukar dg multinod goiterBerkapsul, mendesak sekitarHomogen, 3-10 cmHitam abu2, soft fleshyHemoragis, fibrosis sentralNekrosis sentral -- kista

Mikroskopis :TrabeculerFetal stroma miksomstousColloidSpindel / atipikalhurthlePerjalanan penyakit :Sloly increase insizeUkuran tertentuCepat besar, nyeri, hemoragisJarang T3 dan T4 tinggicold nodule dapat hot

ADENOMA FOLLIKULER

ADENOMA FOLLIKULER

Malignant tumors USA 1991 1000 , 2/3 perempuan, >1% penyebab Papil Ca 75-85%Fol Ca 10-20%Med Ca 5%Anaplastik Ca jarangPatogenesis :1. Radiasi head and neckPembesaran tonsil,timus,acne, irradiasi pd dekade 2 carcinogenik4-9%infant rad Ca 20 th, 70% bom di jepang2. hashimoto limfomaNon toxic goiter

Papillary CaKhas :Hipokhromatik empty nucleidevoid of nucleus (orphann annie eyes)Inti grooveInklusi intranukl eosinofilikpsammomaEncapsulated variantFollikulerTall cell

PAPPILARY CARCINOMA

Follicular CarcinomaPerjalanan peny :Foll Ca tumbuh lambat lanjut irreg,multinodD/ ditegakkan metas (+)/(-)Prognosis :Ukuran primer?Invasi kapsul +/_Anaplasia?Larger invesive Ca5 th surv rate 30%10 th surv rate 20 %

Anaplastic Ca5 %Older, daerah endemik goiterHistologi:Spindle cell Ca dapat fol, papil CaGiant cellSmall cell jarangD/ massa cepat >>Lokal invasive (trakhea)

Medullary CarcinomaNeuroendokrin neoplasma sel parafol:Calcitonin Stroma amiloid20-25% ~ MEN syndrMorfologi:Tumor tersebar 1 lobusNodules kedua lobusFamilial MEN syndr10 th surv rate 90 % sedangkan MEN syndr 10 th surv rate 30-50%

MEDULLARY CARCINOMA