SISTIM ENDOKRIN

Dr. Hj. RESMI KARTINI, MS

Homeostasis seluler diatur :

Sistim saraf
Sistim endokrin
terutama hipotalamus ( pituitari )
Dan sel neuroendokrin APUD
Hormon

Kelenjar endokrin target organ

interaksi melalui reseptor

Reseptor - reseptor
Surface membrane receptors
Hormon polipeptide ( pituitary )
Katekolamin

Cytoplasmic reseptor
Steroid
Nukleus

Intranuclear reseptor
Thyroid hormon
Sitoplasma

HIPOTALAMUS
HORMON STIMULATORY
INHIBITORY

PITUITARY
KONTROL

FEED BACK MECHANISM

KELENJAR ENDOKRIN PERIFER

Pituitary gland
ANT:adenohipofisis Rathkes Pouch
Post : Neuro Hipofisis Floor Ventr III
Post - Vasopresin ( ADH )
-Oxytocin
Ant -Asidofil
somatrroph GH
mammotroph PrL

-Basofil

Corticotroph Proopiomesamocortin

acth,msh,
endorfin,lipotropin
Tirotrof TSH
Gonadotrop: FSH,LH

-Khromofob

Glikoprotein

PATOLOGI
Primer : Lobus Ant
Post
Adenohipofisis 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 )

Hiperpituitari
Adenoma
Karsinoma
(Hipotalamus Stimulasi >>
Pituiti)----- jarang
Adenoma
Monoclonal
Single hormon
Plurihormonal

Manifestasi klinik

Primitif / Pluri potent cells

Morfologi
Mikro adenoma ( < 10 mm )
Mikro adenoma ( > 10 mm )
Mikro adenoma : 40 % unselected
autopsi.
single ,multipel
multiple foci hiperpl
Makro adenoma : Ekpansi dpt erosi
tulang
Sella enkapsul poorly diliputi retikulin
chiasma optikum syaraf kranial
Dasar otak,sinus cavernosus, tlg sfenoid

Mikroskopis :
Uniform sel poligonal
tersusun sheet,cord,nests.
Stroma vascularisasi bertambah
Necrosis ischemik,psammoma bodies
Hemoragik pituit apoplexy
Mitosis /pleomorfik ? Malignancy
metastasis

PITUITARY ADENOMA

PITUITARY ADENOMA

Somatotropic ADENOMAS
Somatotro. acidophilic macro adenoma
GH Akromegali
Gigantisme
jarang
Hiperplasia
Akromegali
Adult Megali :akral,Kepala, tgn,
Kaki,jaw,lidah
Soft tissue

Gigantisme : Children
Sel matur uniform --- granulated
Sebagian pleomorfik asidofil
1/3 BSM Prl bimorfus
Prl granul pada sel neoplastik tidak
terdapat pada darah

Prolactinomas

Sparsely granulated
Hiperplasia jarang
Hiperprolactinemi 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 cells
1/3 Micro adenoma
Kalsifikasi
Sel uniform

sela tursika

Corticotroph tumors
basophilik mikroadenoma
ACTH ------ Hipersekresi kortisol

adrenal
Hiperplasia / multiple micro adenoma
cushings disease
Pro opio melanocortincrookes hyaline changes
khromofobic less well defined cortisol excess
Silent tumor besar induce local changes

Other functioning Adenomas

Gonadotroph tumor 6%
Laki 2 FSH
LH
hipogonad
Perempuan
Gonadotropin sekresi wl pun LH dapat dideteksi serum
Besar
Mikros : Laki-laki Pleom,
wanita :uniform small cell

CARCINOMA
Diferensiasi
Diagnosis Matastase : KGB Bone
Hati dll

Disorders associated with Hypopituitarism

Germ cell T
Kraniofaringioma
Glioma
Ketiga diatas lesions of
hypothal,ant
hipofis hipopituitary
75 % destruksi klinik
Tumor klinik : Diab-insipidus
Growth Acceleration
Delayed puberty

90% hipopituitproses destruksi adeno hipophisis

TU: Nonsecretory adenomas
Sheehans pit.necrosis
Empty sella tursika
Neoplasma .metas.
Pituit apopleksi chemor
Disruption blood supply by sistemic arteritis / or tr
Sinus venosus cavernosus
Distruksi 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 )

MORFOLOGI
Besar silent bertahun-tahun
Null cell adenoma
Oncocytoma
sparsely granules lession
Imunohistokimia FSH, / hormon,
LH

SHEEHANS SYNDROME /
NECROSIS PITUIT POST
PARTUM
Hamil pituitary besar

Hemorr
vasospasmenekrosis.iskemik/
infark lobus anterior
Shock

DIC
Sickle cell anemia
Tr. Sinus cavernosus
arteritis temporal,
traumatic injury pembuluh darah,
DM (lama)

95-99 % destruksi lobus anterior

defisiensi gonadotropic laktasi
menurun (puerperium)
Defisiensi TSH atau hipotiroid
ACTH (insufisiensi adrenocortical)
Infark : soft, pale fibrosis

EMPTY SELLA SYNDROME

Hernia arachnoid deffect diafragma
sella
Tekanan CSF atropi pituitary
empty sella

SINDROMA PITUITARY
ANTERIOR
Jarang
Terutama lesi hipotalamus supraseller
Disfungsi
ADH defisiensi diabets insipidus
Arginin vasopresin:oksitosin kontraksi uterus partus
stim glandula lactating

Neoplastik : tumor supraseller, metas Ca, abses,

meningitis, TBC, sarcoidosis (inflamasi
hipotalamus-hipofisial)
Surgical radiasi hipotalamus-hipofisial
Severe head injury
Idiopatik

Hypothalamik suprasellar tumors

Neoplasma jrg
GLIOMA / Craniopharyngioma

Hipofungsi
pituitary anterior
Hiperfungsi
Diabetes insipidus
Craniopharyngioma
Dari sisa rathkes pouch
Pada sella, suprasellar
Anak, dewasa muda
benign

MORFOLOGI
3-4 cm, solid encapsule, kistik
multilokuler, kalsifikasi
Mikroskopis :

ADENO HIPOFISIAL HIPOFUNGSI

Lorain levi syndrome
GH / hormon lain
Hipoglikemia
gonadotropin
Kraniofaringioma

Frohlichs syndrome
Obesitas
Perkembangan sex arrest
Mental sub normal,
Growth
tumor

Prepubertas--- growth pituitary

dwarfism
sexual retard

HIPOGONADISM

Amenore
Loss of axilla and pubic
Sterillity
Ovarium atropi, genital atropi

Testis atropi, sterillity

Loss of axilla, pubic
Hipotiroid TSH
Hipoadrenal ACTH
Panhipopituit Simmonds

TSH
Iodine in diet
abs

iodine+tirosin

oleh TSH
bowel

T3
monoiodo
and
diiodotirosin
T4

sekresi
stimulasi
oleh TSH

blood

TIROID
Tirotoksikosis (hipertiroidism)
Hipotiroidism
Difus / fokal enlargement (Goiter)
tidak ada hubungan antara lesi morfol
dan klinik

TIROTOKSIKOSIS
Hipertiroidism,
Free T3 , T4
Hiperfungsi tiroid (Graves disease)
hipertiroidism
Non hiperaktif kelenjar tirotoksikosis
Sindrom :
Nervousness
BB (nafsu makan baik)
Palpitasi
Heat intolerance
Rapid pulse
Warm skin
Fatigability
Emosi labil
Kelemahan otot
Perubahan haid
BMR
Tremor tangan
Perubahan mata
Kelenjar tiroid membesar

MORFOLOGI
Vasodilatasi : Periferheat loss
Sirkulasi hiperdinamik general kulit :
warm, moist, flushed
hipertiroidperubahan mata
Graves disease---proptosis perubahan
imunologi
Inflamasi sekunder jaringan retroorbital
jantung
Takhikardi
Palpitasi
Kardiomegali
Aritmia, fibrilasi supraventrikuler

GRAVES DISEASE

THYROTOXIC CARDIOMIOPATHY
Fokus infiltrasi limfosit, eosinofil,
interstisial, fibrosis ringan, fatty
changes
Manifestasi lain:
Otot skelet : atropi, fatty infiltrasi,
infiltrasi limfosit fokal
Hati : minimal fatty changes, fibrosis
periportal, infiltrasi limfosit
Osteoporosis
general lymphoid hyperplasia dg
lymphadenopathy

Graves Disease
< 40 th (85%)
Hipertiroid
Diffuse toxic hyperplasia
Hiperfungsi tiroid
Pemberian iodine >> pada kelainan
(T3 / T4)
tiroid
Jod basedows disease

HIPERFUNGSI TIROID
T3 T4 sirkulasi tirotoksikosis
Terdiri dari :
Graves disease
Toxic adenoma
Toxic noduler goiter

Klinik :
Exophtalmus
Prominent tiroid
BMR
Skin warm, sweaty : heat intolerance
Weakness,hiperkinesia, emotional instability
BB
Glucose tolerance, glukosuria
Nadi , Cardial arrhythmia and failure ( orang tua )
TSH

TIROIDITIS
Tiroiditis interstitial
Palpation tiroid
Superior / inferior tiroid
jarang direct traumatic
Imunologi
Staf, strep, salmonella,
enterobacter, M tbc, jamur (candida,
asper, mucor)

Morfologi
Kelenjar besar

Hasimoto
Sub acute granulomatous tiroiditis
Sub acute limfositic tiroiditis

Riedel struma

HASHIMOTOS THYROIDITIS
/ STRUMA LYMPHOMATOSA
/ LYMPHADENOID GOITER
:
Goitrous hipotir
Non endemic goter (children)
Autoimun disease

Berlangsung lama hipotiroid

hipertiroidhashitoxicosis
Hashimoto Grave

ETIOLOGI
Autoimun
Defek fungsi tiroid spesifik
Supressor T cell
Antibodies tiroid peroksidase
(antimicrosomal antibodies)
AB Spesifik untuk tiroglobulin
TSH reseptor

Morfologi
Kelenjar besar, diffuse, asimetris, kapsul
intak, coklat noduler, Rubbery tissue
Mikroskopis :
Perjalanan penyakit :
usia pertengahan
Hipotiroidism
Atropi
Stadium dini metabolisme normal, fungsi
tiroid, TSH, T3 T4
Prognosa baik: 1-200 lymphoma
Goitrous hipotir
Non endemic goter (children)
Autoimun disease lymphoma

HASHIMOTOS THYROIDITIS

HASHIMOTOS THYROIDITIS

Riedels fibrous thyroiditis

/Riedel struma
Causa unknown
Atropi/hipertropi, fibrosis,firm,abu 2
ca
Kadang : Retroperitoneal fibrosis
( multi fokal fibro sclerosis )
Mikros : fibrosis , infiltrasi limposit
scant,fol tiroid distorsi

Sub acuta granulomatous

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

MORFOLOGI
Tir > > / Fokal asimetris
Opt gland tkena irreg
: lokalisasi firm,kuning putih
ruberry
Histologi :
Patchy Lama
Proses inflam,micro abses
Lanjut folikel rusak / agregat sel
sukar ? sel dari folikel
makropag
multinuclear giant cell (koloid) fibrosis
gran thyroiditis

PERJALANAN PENYAKIT
1. Acute systemic febrile, LED
2. Nyeri, GL > sore throat ,
earache
3. Nyeri << hipertiroid transient
dekstruksi kelenjar hipotiroid
Kerusakan kel T3 T4
Uptake J131 (TSH supresi)

SUB ACUTE GRANULOMATOUS THYROIDITIS

(DE QUERVAINS THYROIDITIS)

SUBACUTE LYMPHOCYTIC
(PAINLESS) THYROIDITIS
? GOITROUS HYPERTHYROID
Fokus infiltrasi limfosit
Jaringan fibrous interstisial
Kel tir >> dan Hipertiroid Amerika utara
15 % grave
Goitrous >> tdk terdeteksi self limiting
disease hipotiroid
?
T3 dan T4

GRAVES DISEASE
Hipertiroid hiperfungsi difuse hiperplasia goiter
Infiltratif ophtalmopathy, dermopathy
Opthalmopathy :
Lid lag
Upper lid retraction
Edem periorbital
Stare
Otot mata lemah
proptosis

Dermopathy:
Edem pinggung kaki, tungkai
Plaque like / noduler
Lokal myxedema

(-) Tirotoksikosis diffuse toxic goiter

USA 12-20 %

ETIOLOGI DAN PATOGENESIS

AUTOIMUN
Ig G antibodi TSH reseptor
Thyroid stimulating AB (TSAb)
Thyroid stimulating Ig (TSI)
Hashimoto
Pada pdrt Graves dpt an.pernisiosa, rheumatoid
arthritis

MORFOLOGI :
Diffuse hyperplasia
80-90 gr
Kapsul intact
Diameter parenkim lunak daging

HISTOLOGI
Cell>> vask
Pseudopapil mushroom, folikel
Koloid , pucat
Stroma jaringan limfoid >>, folikel >>
general lymphoid hypertrophy
PERJALANAN PENYAKIT
Muda tirotoksikosis tir > simetris
Uptake JOD131
Proptosis >> injury cornea, ulserasi,
mata (-)

DIFFUSE AND MULTINODULAR

GOITER
Kerusakan output hipertiroid
kompensasi kad TSH
Hipertropi, hiperplasia epitel folikel
Diffuse/ multi noduler
Tir > hor < eutiroid
1. diffuse non toxic (simple goiter)
2. multinod goiter

Diffuse non toxic (simple) goiter

Pembesaran diffuse
Hiper/hipofungsi
ENDEMIC GOITER
Simple goiter, lokalisasi geografik 10 %
populasi pegunungan
Intake yod hor tir TSH
hipertir, hiperplasia
Ca, flour goiter
Makanan dan sayur

NON ENDEMIC / SPORADIC

SIMPLE GOITER
8:1
Pubertas / Dws muda
TSH
Kehamilan estrogen TBG
1. defek transport jod T3 T4
2. defek organifikasi feed back inhibition
TSH
3.defek dehalogenase
Defek iodotirosin coupling

MORFOLOGI
Stadium hiperplastik, colloid involution
Hiperplastik
Kel >> sedang (100-150 gr)
Difuse, simetris, hiperemik
Histologi : epitel fol kolumner, generasi fol <<,
scanty colloid 500 gr koloid ep.
Flatetened
? Akumulasi koloid not uniform pada tir
Fol >>, << small papil, hiperpl sel
Gelatinous, diameter kilat colloid goiter
T/ jod

Multi noduler goiter

simple goiter multi nod goiter
sporadik endemik
non toxic
tirotoxicosis (toxic multi nod goiter)
plummers disease
Jarang hipotiroid
Tiroid membesar DD/neoplastik
Older ok. komplikasi

Sel tiroid normal-heterogen perbedaan

potensi
Proliferatif
Folikel membesar ruptur hemoragik
jar. Parut kalsifikasi

Morfologi
1. nod hiperplasi folikel, folikel dg
koloid banyak
2. irreguler scarring
3. Hemoragik fokal, deposit
hemosiderin
4. kalsifikasi fokal pd jar. Parut
5. mikrokista

Perjalanan Penyakit
Klinik penting:
Ukuran, lokalisasi massa
Fungsi abnormal biasa : tirotoksikosis
Perbedaan dg neoplasma
CVS 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 serak

Hiperfungsi toksik noduler goiter
Uptake jod 131 , T3 T4
Akumulasi radioaktif tersebar ke dalam
tiroid
Jarang menyebabkan noduler hiperfungsi
Tiroid >> 2000gr 1 atau lebih lobus
menekan trakea, Oesofagus, dan
dibelakang sternum intrathoracic
plunging goiter

Morfologi
Multinod heterogen
Nod batad tidak tegas
Jar. Parut tampak sebagian encapsul
Penamaan yg salah adenomatous
goiter dan multiple coloid adenomatous
goiter
DD/: neoplasma sukar
CT scan
USG
MRI
Biopsi aspirasi
Resiko Ca namun data (-)

NODULER GOITER

NODULER GOITER

Hipotiroidism
Hipometabolisme
Hipotiroid
1. selama fase perkembangan, invasi,
kretinisme physical, mental retard
2. older children/adult myxedema
Akumulasi hidrofilik mukopolisakarid
Pada jar penyokong edem dan kulit
tebal

Kausa
USA hipotiroid, idiopatik primer
tiroiditis autoimun atropik
15-60%
Sustansi ------------TSH reseptor
bloking
auto AB
dapat menghilang spontan
Terapi
Post tiroidektomi >>

Cretinism
Jarang
Retardasi fisik dan intelektual
Pada saat lahir tergantung dr hormonal
efeknya terlihat setelah bbrp minggu-bulan2
Klinik : kulit kering,kasar
Widely set eyes
peri orbital bengkak
hidung lebar,flattened
lidah besar
Jod -pada perkembangan fetal
Agenesis tiroid
Defek biosintese kongenital
Pertumbuhan skelet terganggu, perkembangan otak

Endemik cretinism
endemik goiter
Sporadic cretinism cretinism sporadik atropi

MYXEDEMA
Older child diantara kretin dan dewasa
dg hipotiroid
Adult pelan2
Aktifitas fisik dan mental lambat
Bicara, intelek
Edem preorbita
Kulit tebal, kasar, kering, lidah >>
Facial feature thikened
Letargik keringat banyak, konstipasi, fungsi
motorik
=> Sebagai kretin
Mikros : miofiber edem, striae hilang

TUMORS
NOD
USA, adult, 2-4%, nod daerah endemik
goiter,
90%adenoma, karsinoma 2535kasus/milion
Solitary mass nodules, multinucleated
goiter, kista, pembesaran asimetris
Nod soliter neoplastik
warm/hot nodul benigna
Penderita<40 th mirip neoplasma nod
non neoplastik (mungkin hashimoto,
multinod goiter) older
Laki2 nod hati2
Perempuan >> non neoplastik

ADENOMA
Dari epitel folikel ad. Folikuler
Mikros : fetal,embrional,simple, colloid,
mikro & makrofol
Morfologi :
DD/ sukar dg multinod goiter
Berkapsul, mendesak sekitar
Homogen, 3-10 cm
Hitam abu2, soft fleshy
Hemoragis, fibrosis sentral
Nekrosis sentral -- kista

Mikroskopis :
Trabeculer
Fetal stroma miksomstous
Colloid
Spindel / atipikal
hurthle

Perjalanan penyakit :
Sloly increase insize
Ukuran tertentu
Cepat besar, nyeri, hemoragis
Jarang T3 dan T4 tinggi
cold 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 jarang
Patogenesis :
1. Radiasi head and neck
Pembesaran tonsil,timus,acne, irradiasi pd dekade
2 carcinogenik
4-9%infant rad Ca 20 th, 70% bom di jepang

2. hashimoto limfoma
Non toxic goiter

Papillary Ca
Khas :
Hipokhromatik empty nucleidevoid of
nucleus (orphann annie eyes)
Inti groove
Inklusi intranukl eosinofilik
psammoma

Encapsulated variant
Follikuler
Tall cell

PAPPILARY CARCINOMA

Follicular Carcinoma
Perjalanan peny :
Foll Ca tumbuh lambat lanjut
irreg,multinod
D/ ditegakkan metas (+)/(-)

Prognosis :
Ukuran primer?
Invasi kapsul +/_
Anaplasia?

Larger invesive Ca
5 th surv rate 30%
10 th surv rate 20 %

Anaplastic Ca
5%
Older, daerah endemik goiter
Histologi:
Spindle cell Ca dapat fol, papil Ca
Giant cell
Small cell jarang

D/ massa cepat >>

Lokal invasive (trakhea)

Medullary Carcinoma
Neuroendokrin neoplasma sel parafol:
Calcitonin
Stroma amiloid
20-25% ~ MEN syndr

Morfologi:
Tumor tersebar 1 lobus
Nodules kedua lobus

Familial MEN syndr

10 th surv rate 90 % sedangkan MEN
syndr 10 th surv rate 30-50%

MEDULLARY CARCINOMA