Cushing Syndrom
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Tutor 1 blok 7Cushing Syndrome Iatrogenik
FK Universitas Kristen Maranatha
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Kelompok 16 0710214 Yuniati Valentina
0910154 Prayoga kristianto
1010014 Muhammad Rinaldhi Akbar M
1010020 Kiki Fitria
1010053 Carryn Bestika Sugiharto
1010056 Brigita Widhayu Wiradi
1010070 Juni Royntan Tampubolon
1010110 Meigi Suwarto
1010129 Hans Natanael
1010183 Monica Gloria Komaling
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TERMINOLOGISistem Neuroendokrin = sistem yg merupakan interaksi antara sistem saraf
(nervous) & sistem endokrin.
Striae Lividae = garis yg warnanya biru pd kulit, krn ada pembesaran/peregangan pd jaringan yg menimbulkan perdarahan kapiler halus bawah kulit
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Moon Face = tanda medis, wajah membengkak jd bentuk bundar. Sering dikaitkan dgn Cushing Syndrome (Cushingoid facies) atau pengobatan steroid (steroid facies)
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Buffalo Hump = punguk kerbau, redistribusi lemak di belakang leher
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Anti-pruritus = anti gatal sensasi pada kulit yg menimbulkan keinginan menggaruk
Supraclavicular fat = redistribusi lemak ke daerah sekitar atas clavicula
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CTM = chlortrimeton chlorperieamine, obat alkylamine antihistamin gen. pertama, digunakan utk mencegah gejala alergi. Efek sedatif lemah
HDL = high-density lipoprotein salah 1 lipoprotein utama, memungkinkan lipid spt kolesterol & trigliserida diangkut ke aliran darah berbasis air. Membersihkan kelebihan kolesterol dr dinding pemb.darah dgn mengankutnya kmbl ke hati. Terkecil & terpadat
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LDL = low-density lipoprotein gol.lipoprotein yg bervariasi ukuran & isi, mengangkut kolesterol dr hati ke jaringan dgn menggabungkannya ke dlm membran sel. LDL ↑ berhubungan dgn penyakit kardiovaskuler
GDP = gula darah puasa kadar glukosa dlm darah saat tdk ada asupan kalori, setidaknya 8 jam terakhir sblm pemeriksaan. Utk diagnosis prediabetes & diabetes
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PP = Post Prandial sesudah makan
2 jam PP tes glukosa 2 jam setelah makan, 75g gula dalam 250 cc air, habis dlm 5 menit
Cairan bebas abdomen =
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Nilai dan Batas NormalBMI (Body Mass Index)
Severely underweight < 16.0
Underweight 16 – 18.5
Normal 18.5 – 25
Overweight 25 – 30
Obese class I 30 – 35
Obese class II 35 – 40
Obese class III > 40
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Tekanan Darah (mmHg, menurut JNC VII)
Normal < 120 (dan) 80
Pre-hipertensi 120 – 139 (atau) 80 – 89
Stadium I 140 – 159 (atau) 90 – 99
Stadium II 160 110
Suhu
Hipotermi < 36C
Normal 36 – 37.5C
Febris/pireksis 37.5 - 40C
Hipertermi > 40C
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Ureum
GDP
Normal 75 – 110 mg/dl
Impaired glucose tolerance 111 – 125 mg/dl
Diabetes Melitus > 125 mg/dl
PP (American Diabetes Association) < 180 mg/dl
Natrium 136 – 146 mEq/L
Kalium 3.5 – 5.0 mEq/L
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Kolesterol Total (mg/dl)
< 200 optimal
200 – 239 diinginkan
240 tinggi
Trigliserid (mg/dl)
< 150 optimal
150 – 199 diinginkan
200 – 499 tinggi
500 sangat tinggi
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Kolesterol LDL (mg/dl)
< 70 therapeutic option for high risk patient
< 100 optimal
100 -129 mendekati optimal
130 – 159 diinginkan
160 – 189 tinggi
190 sangat tinggi
Kolesterol HDL (mg/dl)
< 40 rendah
60 tinggi
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ANATOMI, HISTOLOGI, DAN FISIOLOGI
KELENJAR ADRENAL
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Anatomi Glandula suprarenalis berwarna kekuningan, ada sepasang, terletak
retroperitoneal di antara aspek superomedialis ren dan diaphragma, disekeliling jaringan ikat yang banyak mengandung capsula adiposa (perinephric fat).
Glandula suprarenalis dexter berbentuk pyramidalis, lebih apical dibandingkan dibandingkan yang kiri, terletak di anterolateral crus dextrum diaphragmatis dan berhubungan dengan vena cava inferior di anteromedial dan hepar di anterolateral
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Glandula suprarenalis sinister berbentuk rescent (sabit), terletak pada batas medial ren sinister dari hilus sampai kutub superior, berhubungan dengan spleen, gaster, pancreas, dan crus sinistrum diaphragmatic.
Ukuran tebal sekitar 1 cm, lebar apex 2 cm, dan lebar basal sampai 5 cm. berat setiap glandula suprarenalis 7-10 gram
Glandulae suprarenales terdiri dari bagian cortex dan medulla yang berbeda asal embriologik dan fungsinya, dibentuk dari 2 lapisan germinal yang berbeda.
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Arteri Arterialae suprarenales superiors, cabang dari arteriae phrenicae inferiors.
Arterialae suprarenales mediales, cabang dari aorta abdominalis
Arterialae suprarenales inferiors, berasal dari arteriae renales.
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Persyarafan Semua sel-sel medulla suprarenalis dipersyarafi oleh akhiran cholinergic
dari neuron sympaticum preganglionicae.
Persyarafan glandula suprarenalis berasal dari plexus coeliacus dan nervi splanchnici abdominopelvici (major, minor, imus).
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HISTOLOGI
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HISTOLOGI Korteks Adrenal
1. Zona glomerulosa menghasilkan hormon mineralokortikoid aldosteron
2. Zona fasciculate menghasilkan glukokortikoid (kortisol, kortikosteron) dan hormone seks.
3. Zona retikularis yang berkembang setelah lahir dan tampak sekitar umur 3 tahun, menghasilkan glukokortikoid dan androgen.
Medulla Adrenal
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FISIOLOGI KELENJAR ADRENAL
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HORMON KELENJAR ADRENAL
Korteks Adrenal
1. Glukokortikoid
2. Mineralokortikoid
3. Hormon Seks
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Jenis & Kerja Glukokortikoid
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Kortikosteroid dibagi 2 :•Glikokortikoid : metabolisme KH, protein, lemak•Mineralokortikod : mengatur kadar elektrolit dan airJENIS-JENIS Glukokortikoid :•Jangka pendek (8-12jam) : hidrokortison, kortison•Jangka sedang ( 18-36jam) : prednison, prednisolon, triamsinolon•Jangka lama (1-3hari) : betametason, deksametason,parametason
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PRINSIP Penggunaan Glukokortikoid
1. Dosis efektif tiap penyakit tiap pasien harus dievaluasi terus.
2. Dosis tunggal besar umumnya tidak berbahaya
3. Penggunaan beberapa hari, tanpa KI spesifik, tidak berbahaya kecuali dosis sabgat besar
4. Bila penggunaan diperpanjang (> 2mgg) atau melebihi dosis, insidensi efek letal akan bertambah. Bila terpaksa, harus diberi diet tinggi protein dan Kalium.
5. Bukan merupakan terapi kuratif, hanya bersifat efek anti inflamasinya (kec, insufisiensi adrenal)
6. Penghentian tiba2 pada dosis tinggi & jangka panjang mempunyai resiko insufisiensi adrenal hebat dan kematian.
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INDIKASI Glukokortikoid
Terapi pengganti pada insufisiensi adrenokortikol primer (Addison’s desease)
Terapi pengganti pada insufisiensi adrenokortikol sekunder
Diagnosis Cushing syndrome
Terapi pengganti pada hiperplasia adrenal kongenital
Menghilangkan gejala peradangan
Pengobatan alergi
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KONTRAINDIKASI Glikokortikoid
Usia lanjut (Osteoporosis)
Penderita gastritis, hipertensi berat, infeksi kronik spesifik , anak2, wanita hamil.
MEKANISME KERJA
Molekul hormon (obat)
Memasuki sel scr difusi pasif
Beraksi dengan resptor
Kompleks reseptor steroid
mengalami perubahan konformasi
Nukleus &kromatin
Transkripsi RNA, sintesi protein
Induksi efek fisiologis
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EFEK Glukokortikoid
Menimbulkan metabolisme perantara normal : bantu glukoneogenesis.
Meningkatkan resistensi terhadap stress
Merubah kadar sel darah dalam plasma : penurunan eosinofil,basofil,monosit. Peningkatan HB, eritrosit, trombosit
Anti inflamasi : menekan respon peradangan
Mempengaruhi komponen lain sistem endokrin : penghambatan kortikotropin
Efek pada sistem lain : dosis tinggi merangsang asam lambung
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EFEK SAMPING Glukokortikoid
Saluran cerna : hipersekresi asam lambung, ulkus peptikum
Susunan saraf pusat : insomnia, gelisah,mudah tersinggung
Tulang : osteoporosis, fraktur
Kulit : striae, purpura
Mata : glaucoma, katarak
Darah : kenaikan Hb, eritrosit
Pembuluh darah : Kenaikan tekanan darah
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Cushing’s Syndrome(Hypercortisolism)
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definisi Sebuah kelainan yang disebabkan hipersekresi dari hormon yang dibuat oleh
kelenjar adrenal khususnya kortisol yang ditandai dengan obesitas,hipertensi,striae,amenorrhea,hirsutism,hingga basophilic tumor di kelenjar pituitary
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etiology1. Terkait ACTH :
a.adenoma hipofisis
b.ACTH ektopik
2.Tidak terkait ACTH :
a.adenoma adrenal
b.carcinoma adrenal
c.glukokortikoid eksogen
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Insidensi dan epidemiologi Wanita : pria = 4:1
Kebanyakan terjadi di dekade ke 3 hingga 4 kehidupan
Jarang terjadi pada anak-anak
Ditemukan 700.000-2.400.000 kasus/tahun
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Faktor resiko Penggunaan glukokortikoid jangka panjang
Jenis kelamin
Tumor adrenal
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klasifikasiUmum :
1.Cushing syndrome
2.Cushing disease
3.Paraneoplasama cushing
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Klasifikasi cushing syndrome:
1.Hiperplasia adrenal
2.Hiperplasia noduler adrenal
3.Neoplasma adrenal
4.Penyebab iotrogenik
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Patogenesis
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Exogenous vs EndogenousExogenous : hormon yang berasal dari luar tubuh (kortikosteroid
[glukokortikoid] untuk mengobati penyakit tertentu [prednison & prednisolon], ACTH sintetik)
Endogenous : hormon yang berasal dari dalam tubuh (ACTH Dependent & ACTH Independent)
ACTH Dependent (80%): - Pituitary Tumors (60%)
- Lung Cancers (5%)
ACTH Independent (20%): - Benign adrenal tumors (adrenoma) (25%)
- Malignant adrenal tumors (adrenal cell
carcinoma) (10%)
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Patofisiologi dan GK
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Patofisiologi• The accumulation of adipose tissue in the:
- trunk (TRUNCAL OBESITY)
- facial (MOON FACE)
- cervical areas (BUFFALO HUMP)
• Transient weight gain from sodium and water retention mineralcorticoid effects!!
• Cortisol-induced insulin resistance, increased gluconeogenesis and glycogen storage by the liver GLUCOSE INTOLERANCE
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• Hypercortisolism bone resorption, inhibits bone formation, decreases intestinal calcium absorption, increases renal calcium excretion OSTEOPOROSIS (pathologic fractures, vertebral compression fractures, bone and back pain, kyphosis, and reduces height)
• Loss of collagenous support around small vessels suspectible to rupture EASY BRUISING
• Increased adrenal androgen levels increased hair growth (HIRSUTISM), ACNE, OLIGOMENORRHEA
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Gejala Klinis
• Decrease libido in men and women 100%
• Obesity or weight gain 97%
• Plethora 94%
• Round face 88%
• Menstrual changes 84%
• Hirsutism 81%
• Ecchymoses 62%
• Lethargy, depression 62%
• Striae 56%
• Weakness 56%
• Electrocardiographic changes or atherosclerosis 55%
• Dorsal fat pad 54%
• Edema 50%
• Abnormal glucose tolerance 50%
• Osteopenia or fracture 50%
• Headache 47%
• Backache 43%
• Reccurent infections 25%
• Abdominal pain 21%
• Acne 21%
• Female balding 13%
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Komplikasi Diabetes (Diabetes tipe II)
Obesitas
Osteoporosis
Fraktur
Batu Ginjal
Hipertensi
Poor healing
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Diff.Diagnosis
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Pencegahan Hindari konsumsi kortikosteroid
Bila harus mengkonsumsi kortikosteroid perhatikan dosisnya
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Penatalaksanaan Farko
- Ketokenazol (600 – 800mg / hari)
u/ menekan kadar kortisol
KI : kehamilan
ES : sakit kepala, sedasi, mual, mens tidak teratur, ↓libido, impotensi, ginekomastia
- Metyrapone (1gr/hari 4,5gr / hari)
u/ menekan kadar kortisol dengan menginhibisi 11β hidroksilasi
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- Aminogluthemide (1 – 2 gr/hari)
u/ menekan kadar kortisol
ES : Mengantuk, sakit kepala, pruritic rash, hipotiroidisme, gondok.
- Mitotan (2-3gr/hari 8-10gr/hari)
u/ menekan kadar kortisol
KI : wanita usia subur
ES : gangguan GIT (anoreksia, diare, muntah), gangguan neuromuskular (lesu, somnolen, pusing)
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- Mifepristone
inhibitor kompetitif ikatan glukokortikoid dengan reseptor
Non farko
- kortikosteroid tapering
- edukasi
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Prognosis Quo ad vitam : Dubia ad Bonam
Quo ad sanationam : Dubia ad Bonam
Quo ad functionam : Dubia ad Bonam
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Sumber Pathologic Basis of Disease 8th ed. Robbins and Cotran
Pathophysiology 6th ed. McCance
Harrison’s Internal Medicine 17th ed.
Cecil Medicine 23rd ed.
http://en.wikipedia.org/wiki/Cushing's_syndrome
http://www.medicinenet.com/cushings_syndrome/page2.htm
http://endocrine.niddk.nih.gov/pubs/cushings/cushings.htm
http://www.endocrineweb.com/conditions/cushings-syndrome/diseases-adrenal-cortex-cushings-syndrome
http://www.wrongdiagnosis.com/c/cushings_syndrome/complic.htm