PARATIROID

Dr.Hj.Resmi Kartini,MS

Bagian Patologi Anatomi

FUNGSI :

1. PTH → Mobilisasi Ca DR Tulang 2. Reabsorpsi tubulus ginjal ↑ (Ca) 3. Promotes Prod Ginjal : 1,25 (OH)2 D3 → Active in intestinal Absorpsion of Ca 4. Kadar posfat Serum ↓ →Posfaturi ↑ PTH Resorpsi tulang → Ca + P ↑ (darah)

Hiper Paratiroid

Primer → Krsk pd kelenjar → Hiper sekresi hormon. Paratir → Hiper Kalsemi Hipo Posfatemi Sekunder Hipo Kalsemi → PTH ↑ Hipo Paratiroid

Primary Hiper ParatiroidPTH ↑ →1. Resorpsi tulang ↑ , mobilisasi Ca Skelet ↑2. Renal Tub. Reabsorpsi ↑

Retensi Ca3. Sintesis 1,25 (OH)2 D3 renal ↑

− Absorpsi C it ?? ↑

Hiper Kalsemia ← Hiper paratir ↑ (90%) / Cancer

- Adenoma 75-80%- Primary Hyperplasia (difuse / NOD) 10-15%- Ca Paratir < 5%

Kad Ca serum ↑ tidak mbr efek pd fungsi autunom tumor, Adenoma, Ca,Hiperplasia kel. Trs ?? Hiperfungsi akibat defek mekanisme reseptor Ca chief

cell –normal → Kad. Ca Serum.

USA ♀ 3:1

EROPA Dekade ? →

Asimptomatik

D/ Weakness

Mudah Lelah

Disfungsi Afektif

Hiper Calseuria 10% penderita

Osteitis Fibrosa Cystica

(Hiperaktif Osteoclas)

MEN

Adenoma

Soliter 0,5 – 5 cm , soft , merah, tan kapsul, kel inferior

Kel yg tidak terkena supresi, kecil

↑ Chief cell sheet, trabekula, folikuler oxyphil cell variasi ukuran inti.

Transitional cell

Infark , nekrosis

Hiperplasia Primer

Sporadik/ Men Syndr I II aKeseluruh Kel terkena 7% , dpt 2 kel asimetris, >> 0,5 –1GR m ↑ chief cell difus, nodul(water, oxifil)Jr, fibrous mengelilingi

→ Solid sheets, nest , trabekula, foll cell bi nukl Sel lemak

Karcinoma Abu 2 putih,masa irreg,io gr Biasa pada I kel Histol : Uniform,pleo, nod,trabekuler,solid Khas kapsul jar fibrosa MALIGNANCY invasi lokal,metastase rekuren lokal 1/3 kasus Metastase 2/3 kasus Kematian komplikasi hiperparatir

Perjalanan penyakit :Klinik :Ginjal : nefrolitiasis nefrokalsinosisSkeletal : osteitis fibrosa cyctica ostoe porosisGit : n,v, ulcus peptikum pankreatitisCVS : sakit kepala,lethargy,depresi,memori negatif,seizureOtot :kelemahan umum.Perubahan kulit dan mataD/ ← hipercalcemia,hipoposfatemi,fatig

Hipoparatiroidism

1.Op.tiroidektomi 2.Kel.Kong.Paratir - →Di Georges’s Syndr. 3Py Autoimun→Polyglandular autoimun sy Adrenal, ovarian failure,kandidiasis

muko kutaneus,An.Pernisiosa

4.Sundry ,Familial autosomal dan metabolic syndr .( hipomagnesemia )

Klinik : Neuromuscular exitability← kad Ca ion

serum ↓ N VII →kontraksi otot mata,mulut hidung

→ ( Chvostek’ Sign ) Oklusi aliran darah lengan ,tangan Spasme karpal ( Trousseaun’s sign ) Titani,spasme karpo pedal Stidor laring,convulsi

ADRENAL

Normal adrenal steroid biosynthesis

cholesterol

↓

pregnenolone 3 17α L

Progesteron → 17α-hydroxyprogesterone → dehydroepiandrosterone

↓21 ↓21 ↓3 A

Deoxycorticosterone deoxycortisol androstenedione → estrone

↓11 ↓11 ↓17β

Corticosterone cortisol testosterone

↓18

aldosterone

ADRENAL

Stress akut → lipid depletion → berat↓ Prolong stress Penyakit kronik → Hiperplasia dan hipertropi sel korteks

Zona glomerulosa → mineralokortikoid Zona fasciculata → Zona retikularis → glukokortikoid Medula katekholamin

MINERALOKORTIKOID Aldosteron reabsorbsi Na ekskresi K

GLICOCORTICOID Cortisol

Inhibisi efek uptake glukosa jaringan Glukosa intolerance Hiperglisemi DM

Absorbsi Ca & P ginjal ↓→ osteoporosis

TESTOSTERON

HIPERFUNGSIHIPER ADRENALISM Sindroma cushing, cortisol ↑ Hiper aldosteronism Adreogenital syndrome : androgen ↑

SINDROMA CUSHING Hipercorticolism Klinik :

Obesitas 85-90% Moon face 85% Weakness, fatigability 85% Hirsutism 75% Hipertensi 75% Plethora 75% Glucose intolerance / DM 75/20 % Osteoporosis 75% Neuropsichiatric abnormal 75-80% Menstruasi abnormal 70% Skin striae (lower abdomen) 50%

Patogenesis1. Pemakaian glukokortikoid

imunosupresi pd transplantasi

2. ACTH pituitary 65-70% ♀3. Non endokrin neoplasma ♂ dekade 5-6

prod ektopik ACTH / CRH → hiperplasia↑ →small cell Cacarcinoid bronchiolus, pankreasmalignant thymomafeokhromocytomamedullary ca tiroidgastrinoma

4. Adenoma, ca, nod hiperplasia → 20-25%ACTH indepentLesi adrenal auto → autonomous secresi kortisol (hiper)

Adenoma, Ca → adult Ca → children Ca→↑ hipercortisolism → Neoplasma unilat kelenjar lain atropi ← ACTH Supresi → Adrenal cushing syndr →

Cortisol ↑ACTH ↓

MORFOLOGI : Lesi2 dasar cushing syndrome

Pituitary adrenal

PITUITARY :Cortical efek feed back corticotrofNon tumor (tumor)→ Crooke’s deg.hialin basofil

Basophilic microadenoma Bosophilic macro adenoma Granulated chromophobic adenoma Hiperplasia difus corticotrof

ADRENAL Diffuse hiperplasia Nod hiperplasia Adenoma, Ca jarang Atropi korteks

bilateral : glucocorticoid exogen

DIFFUSE HYPERPLASIA

60 -70 % KASUS Kel adrenal >> 25-40 gr Korteks melebar Lipid poor retikularis Sel-sel fasikulata normal

NOD Hyperplasia 15-20% Bilateral 0,5 – 2cm, kuning nod tersebar Dipisahkan daerah korteks luas Sel lipid laden, lipid poor Inti variasi, binukleus 20-50 gr ACTH ↑→ autoantibodi reseptor ACTH Diffuse micronodul

Unilat, nod hitam pigmen, kecil : lipofusin, neuromelanin

Sel kecil, kompak, pleo, rgn Dapat familial, autosomal dominan

CUSHING’S SYNDROME Hipersekresi kortisol, banyak terjadi pada wanita, dapat pula

mengenai laki2dan anak. Manifestasi klinik : cortisol >>

Deposisi lemak→striae katabolisme protein →muscle wasting, weakness→striae Protein sintesis <<→muscle wasting, weakness→striae Gluconeogenesis →hiperglikemia dan glukosuria Depresi reaksi imun → tendensi infeksi bakteri Supresi growth hormon → pertumbuhan anak ↓ Adipositas pada wajah, leher Osteoporosis→ khyposis Hypertension Virilism pada wanita

Penyebab : Adenoma korteks adrenal, adenokarsinoma Pituitary adenoma → acth ↑ Bronchial carcinoma, carcinoids, pancreatic tumours Pemakaian lama glukokortikoid atau terapi ACTH

Hiperaldosteronism Primer1. Sekresi aldosteron independent khronik (↑↑)2. Sistem renin angiotensin independen

iskemi ginjal, edema kroniksekunder hiperaldosteronism

Khas : aktifitas renin plasma supresi hipokalemia retensi Na hipertensi

ETIOLOGI :- Adenoma soliter conn’s syndrome 65 %- hiperplasia bilateral idiopatik adrenal 30 %- Glukokortikoid supressible hyperaldosteronism- Familial non glukokortikoid supresPenyebab ini temukan pd 0,05 - 0,2% penderita hipertensi

ADENOMA dan CARCINOMA ADENOMA

Kapsul tipis, <30gr Mikroskopis :

Sel kortikal lipid rich, lipid poor Variasi sel rgn True neoplasma ? Nod hiperplasia /

CARCINOMA kapsul (-), besar 200-300gr, sel anaplastik Perjalanan penyakit :

D/ kortisol ↑ → hidroksikortikoid T/ ?

GLUCOCORTICOID SUPPRESSIBLE HYPER ALDOSTERONISM Jarang, familial, pengaruh ACTH Supresi ← pemakaian dexametazon exogen Perjalanan penyakit :

Hipertensi, hipokalemi ← K ginjal sekresi Manifest neuromuskuler (weakness, parestesi, ggn

visual, tetani) Retensi Na -- edem → hipertensi → Decom cordis

Diagnosa : PHA : aldosteron ↑renin ↓

Causa ? Adenoma → T/ Hiperplasia

HIPERPLASIA ADRENAL KONGENITAL / ADRENOGENITAL SYNDROME Jarang, D/ sukar Hermaproditism Pseudohermaproditism Virilium (♀) Prekok (♂) Androgen syndr → adrenal virilium ← Ca adrenal sekresi androgen

Kong metab errors (enz biosintesis) Steroid cortical (cortisol)

Cortisol ↓→ ACTH ↑ (hiperplasia adr) Enzim terganggu → aldosteron

→ cortisol N

Morfologi

ALDOSTERON PRODUCING ADENOMA Soliter, kecil < 2cm,

kiri, kapsul, ♀ dekade 4-5

Ø yellow, terang, tdd sel korteks, lipid laden

~ sel fasiculata, uniform

Pleomorfik, anaplasia (-)

HIPERPLASIA IDIOPATIK BILATERALSel zona

glomerulosa hiperpla difus ? Fokal dg diselingi nodul adrenocortical kecil (lipid laden)

HIPOFUNGSI KORTEKS ADRENAL (HIPOADRENALISM) Cause : lesi anatomik

metabolik → Steroid ↓ ACTH ↓ (sekunder)1. insuf adrenocortical akut primer (adrenal crisis)2. insuf adrenocortical kronik primer (addison”s

dissease)3. insuf adrenocortical sekunder

INSUFISIENSI ADRENOCRTICAL ACUTE PRIMER JARANG:1. Krisis penderita ionsuf adrenal kronik ← stress

→ steroid ↑, respons ↓2. pemakaian steroid → adrenal ↓

adrenalektomi → stress, adr supres 3. Destruksi adrenal masif

- neonatus partus lama/sukar, trauma, hipoksia →hemoragik adrenal- post op dilatasi infeksi → hemor adrenal- bakteriemi → hemoragik masif adrenal → water house frederick syndrome

MORFOLOGI

Tergantung penyebab Adrenalitis autoimun Norm : leaf like structure Histologi:

Atropi difus zone2, sel lipid <<, kecil, keriput, Lipofusin sitoplasma ↑ sebukan sel limfosit, plasma, makrofag Medula adrenal (-)

PERJALANAN PENYAKIT

Glukokortikoid ↓ Mineralokortikoid ↓ klinik :

Weakness, fatty, anorexia, BB ↓ Hipotensi, hiperpigmentasi kulit

Na Cl Bikarbonat Insuf adr, cor, primer : ACTH

WATERHOUSE-FRIDERICHSEN SYNDROME Jarang Catastrophic syndr :

1. meningokok, gonokok, pneumokok, stafilokok → septikemia

2. Hipotensi progresif → shock3. DIC → purpura skin4. Insuf adrenocortical (rapid) → hemor adr bilat masif

Bacterial seeding → P.D kecil (adr) → DIC,endotoxin → vaskulitis

hipersensitivity vaskulitis Histologi : hemoragik medula

Insufisiensi Adrenocortical Kronik Primer ( Addison’s Disease ) Jarang ←Destruksi kronik kortex adrenal Insidious → sampai 90% destruksi Adult, white, ♀ Etiologi & patogenesis: peny yg mengenai korteks adrenal :

limfoma, amiloidosis, sarcoiodosis, hemokhromatosis, jamur, hemor adr

Adrenalitis autoimun 60-70%TBC kort, med poliglandular syndr, tipe :Metas Ca

1. candidiasis, hipoparatiroid, insuf adrenal2. Adrenal, insulin dependen, DM, Tiroid disease (Schmidt synd)3. Poligland adrenal (-)Anti adrenal antibodi ↑

Insufisiensi adrenocortical sekunderMetastatic cancerInflamasi → hipotalamus → ACTH ↓ →Infark pituit hipoadrIrradiasiGlukokortikoid pemakaian lama→ACTH ↓Adrenal fungsi ↓Hiperpigmentasi of addison’s disease (-)Hor melanotropic↓Cortisol ↓, androgen ↓, aldosteron sintesis N→Malfungsi pituit No mark hiponatremi,hiperkalemi

Hipofungsi Korteks Adrenal Defisiensi mineralokortikoid dan glukokortikoid Hipofungsi akut:

Acute failure reabsorpsi Na dan ekskresi K Kegagalan glukoneogenesis → hipoglikemia dan

sensitifitas insulin ↑ Kematian disebabkan oleh :

Hipovolemia syok Hiperkalemia cardiac irregularity

Destruksi medula dan defisiensi katekolamin → syok

Penyebab kematian yg plg sering adalah septikemi krn meningococcus → nekrosis korteks dan gross hemoragis pada medulla

MEDULA ADRENAL Sel neuroendokrin

Katekholamine Epinefrin Norepinefrin Dopamin Histamin Serotonin Renin Khromogranin A Neuropeptide hormon

Extra adrenal system Paraganglion :

Bronchiomeric Ontravagal aorticosimpatetik

Patologi : tumor Pheochromocytoma Neuroblastoma ganglioneuroma

PHEOCHROMOCYTOMA Jarang Catecholamine induced hypertension → T/ op Hipertensi → 0,1-0,3% akan pheochromocytoma ~ Cushing syndrome

Endocrinopathy 85 % medula adrenal

Extra adrenal paraganglia → Paraganglioma

95% sporadik 10% autosomal dominant Familial – men – anak ♂ , bilateral Non familial 40-60 th ♀

MORFOLOGI

Pada MEN syndrome : adrenal difus / noduler hiperplasia / neoplasma

Dikatakan berasal dr hiperplasia 100 gr (1-400 gr) Batas jelas, fibrous trabekula, vaskularisasi (+),

lob patern Ø Abu pucat, coklat Hemor nekrosis, kista - T besar

HISTOLOGI

Sel tumor sitoplasma > Inti kecil, sentral di batas septa fibrovasc ~ Trabekula , cluster Pleiomorfik ~ alveol, bizzare, giant Sel tumor dapat pada sinusoid dan kapsul →

bukan indikasi malignant Kriteria malignancy – metastasis → KGB, hati,

paru, tulang Syrvival metast < 3th

PERJALANAN PENYAKIT

Klinik : hipertensi paroxysmal attack ← stress, exercise, change of postureDHR tumor palpation

→ katekolamine→ cong heart failure, edem pulmo, MCI, fibrilasi ventrikel, hemor serebri → †

Katekolamine cardiopathy/catecholamine heart muscle disease

D/: urine : Ca, metanefrin, VMA → iskemik ← vasokonstriksi , direct toxicity

→ sakit kepala, ansietas, takut , tremor, fatique, nausea, vomitus, nyeri abdomen

THYMUS1. Development disorders

1. hipoplasia/aplasia2. kista

2. Hiperplasia 3. Thymoma

HIPERPLASIA :Thymic foll hyperplasiaKGBPD : inflamasi kronik

imunologikmiastenia gravis 65-75% kasus

THYMOMA Sel epitel thymus Benign thymoma cito & biol benign Malignant thymoma

Tipe I : sitologi benign biological agresif, invasi lokal, jarang distant spread

Tipe II : “thymic Ca” sitol malignant

Adult, > 40 th, ♀~♂Mediastinum ant, sup or

Kadang leher, tiroid, hilus paru20-30% dari tumor anterosuperior mediastinum

MORFOLOGI

Lobulated, abu2 putih, 15-20 cm

Nekrosis kistik, kalsifikasi (→ biological benign)

Encapsulated, 20-25% penetrasi kapsul → infiltrasi jar peritimik

MIKROSKOPIS Sel epitelial, infiltratif, limfosit non

neoplastik Benign:

Sel epitelial sel medulla, elongated, spindelProd “ medullaey thymoma”Sel epitelial plump, bulat, cortical typeMarsall’s corpuscle jar

MalignantTipe I :

Lokal invasive, metast 20-25% of thymoma Sel epitelial: cortical cell, sitoplasma >> Inti vesikuler bulat, spindel Palisade P.DPenetrasi → invasi capsul

5 th surv rate 50 %- 90% excisi komplit

Tipe II :Makros : fleshy, invasif → metast- ↑ Squamous Ca, well, poorly dif- Limfoepitelioma : sel anaplastik kortikal, limfosit N- Sarcomatoid- Basaloid- Clear cell

PERJALANAN PENYAKIT

Insidentil Clinical attention :

40 % imaging study Simp local pressure 50 % miastenia gravis 10% sindroma paraneoplastik sistemik

(grave’s disease, an pernisiosa, dermatomiositis-poliomiositis, sindroma cushing) ?

PINEAL GLAND

PinealomaPinealoblastomaPineositoma

Morfologi :

PINEOBLASTOMA Young Soft, friable, abu, hemor, nekrosis Invasi struktur sekitar Histologi :

Sel pleomorfik, Ø 2-4 x RBC Inti besar hiperkromatik, mitosis Large/poorly rosette

Metastasis CSF

→ Hidrosefalus

Survival jarang 1-2 th

PINEOCYTOMA Adult, slowly, batas tegas Massa abu2, hemor Histologi :

Glial, neural difLargely astrosimatous, pineosit (bulat,oval)Pseudorossette, dibatasi sel pineosit →Sentral massa eosinofil, fibrovascPerjalanan penyakit - 7 thKlinik penekanan → ggn visual, sakit kepalaMental deterioration, demensia

DEFISIENSI 21 HIDROXILASE

1. Salt wasting adrenogenitalism

2. Simple virilizing adrenogen

3. Nonclassic adrenogenasimtomatik

androgen ↑ anak / pubertas

1. in utero Lahir → salt wasting Hiponatremia Hiperkalemia → Asidosis Hipotensi Cardiovasc collaps †

2. aldosteron↓ RGNtestosteron ↑

hiperplasia adrenal

3. D/ defek biosintesis steroidogenesis

genetik

AUTOSOMAL RECESSIVE

MORFOLOGI ;Defek sintesis cortisol →ACTH ↑→ hiperplasia bilateral adrenalBerat 10-15 kØ Korteks lebar, coklatLipid depletion 2 retic/glom→Nod kecil

FAMILIAL SYNDROME WITH PHEOCHROMOCYTOMA MEN tipe II atau IIA

Medullary thyroid carcinima dan Ccell hyperplasia Pheocromocytoma dan Adrenal meduillary hyperplasia Parathyroid hiperplasia

MEN tipe III atau IIB Medullary thyroid carcinima dan Ccell hyperplasia Pheocromocytoma dan Adrenal meduillary hyperplasia Mucosal neuromas Marfanoid features

Von Hippel-Lindau Renal hepatic, pancreatic, and adrenal medullary hyperplasia Renal cell Ca Pheocromocytoma Angiomatosis Cerebellar hemangioblastoma

Von Recklinghausen Neurofibromatosis Café ua lait skin spoil Schwannomas, meningiomous gliomas Pheocromocytoma

Sturge-Weber Cavernous hei Cavernous hemangioma pada cranial nerve pheocromocytoma