Cushing's Syndromme
Cushing's Syndromme
ADRENAL
- Cushings Syndrome OLEH :
Woro Harjaningsih
Definisi
adalah kondisi klinik sebagai akibat dari paparan
kronik glukokortikoid menyebabkan kadar
glukokortikoid dlm sirkulasi berlebihan.
disebut juga sebagai
hiperadrenokortikalisme
Hiperadrenalkortikalisme
Hiperkortisolisme
Penyebab paling umum : sekresi berlebih ACTH
dari kelenjar hipofisis anterior (Cushings
disease)
ETIOLOGI
A. Cushings disease :
Dapat tjd :
secara spontan cushings syndrome
spontaneous atau , merupakan penyebab
terbesar, kejadian kira2 2 4 kasus / juta
populasi dan pd wanita 9 X lebih banyak drpd
laki-laki
sebagai hasil pemberian kronik (jangka
panjang) kortikosteroid Cushings syndrome
iatrogenic
Patofisiologi
Patofisiologi
Penyebab dapat dibagi 2 kategori :
ACTH-dependent peningkatan kadar
kortisol tergantung pada ACTH dan tidak
dapat menekan sekresi ACTH dari
hipofisis
ACTH-independent peningkatan kadar
kortisol tidak tergantung ACTH (autonom)
dan dapat menekan sekresi ACTH dari
hipofisis
Klasifikasi
ACTH dependent
Cushings disease
Ectopic ACTH syndrome
Ectopic corticotropin-releasing hormone syndrome*
ACTH independent
Iatrogenic
Adrenal adenoma
Micronodular hyperplasia*
Macronodular hyperplasia*
Ket : ACTH : Adrenocorticotropin hormone
*
: accounts per 1 percent or less of cases
(Adapted with permission from Orth DN Cushings Syndrome. N
Engl. J.
Med, 1995 ; 332 : 791 803)
Adrenal tumor
Carcinoma dan adrenal
adenoma primer tidak di
bawah kendali
hipotalamus-hipofisis dan
kmd secara autonom
mensekresikan lebih
kortisol
Hiperkortisol menekan
produksi ACTH hipofisis
menyebabkan atrofi
korteks adrenal
Manifestasi Klinik
FUNGSI KORTISOL
Memelihara tekanan darah dan fungsi kardiovaskuler.
Menurunkan respon inflamasi sistem imun.
Menyeimbangkan efek insulin dalam memecah
glukosa untuk energi.
Mengatur metabolisme protein, karbohidrat, dan
lemak.
Fungsi terpenting : membantu tubuh terhadap respon
stress.
(kadar kortisol wanita pada kehamilan 3 bln terakhir
dan atlit secara normal tinggi).
dmk juga pada orang2 dg depresi, alkoholisme,
malnutrisi dan gangguan panik.
GEJALA
Obesitas tubuh bagian atas, muka bulat, peningkatan
lemak sekitar leher, lengan dan kaki kurus, pada anak-anak
pertumbuhan lambat.
Gejala lain : kulit fragile, kurus, memar dan tidak sehat,
kulit warna ungu pink pada perut, paha, lengan dan
payudara.(striae)
Tulang rapuh dan bengkok, patah tulang (fraktur) pada
tulang rusuk (iga) dan tulang belakang.
Sangat lelah, otot lemah, tek. darah dan kadar gula darah
tinggi, irritabilitas, ansietas, depresi.
Pertumbuhan rambut pada muka, leher, dada, perut dan
paha (pada wanita)
Periode menstruasi tidak teratur/ terhenti.
Penurunan libido sex pada laki-laki
Moonface
Moonface
Striae
DIAGNOSIS
Berdasarkan tinjauan riwayat medis pasien, pemeriksaan
fisik, dan test lab.
X ray : utk menentukan lokasi tumor.
24 urin 24 jam bebas kortisol
paling spesifik, kadar > 50 100 g / hari utk dewasa
cushings syndrome
Test Supresi Dexametason
utk membedakan peningkatan ACTH karena adenoma
hipofisis dan tumor ektopik.
Test Stimulasi CRH
utk membedakan antara adenoma hipofisis dengan
sindroma ACTH ektopik atau tumor adrenal penghasil
kortisol
DIAGNOSIS
Visualisasi langsung Kelenjar Endokrin (Imaging
Radiologi)
- melihat ukuran dan bentuk kelenjar hipofisis dan
adrenal serta menentukan jika ada tumor.
- dengan CT ( Computerized Tomography) scan dan MRI
(Magnetic Resonance Imaging).
Sampling Sinus Petrosal
- test terbaik utk membedakan penyebab Cushings
syndrome antara hipofisis dengan ektopik.
Test Dexametason CRH
- membedakan Cushings syndrome dengan Pseudo
Cushings Syndrome secara cepat.
- Peningkatan kadar kortisol selama test menunjukkan
adanya Cushings Syndrome
Pseudo-Cushing's syndrome is a
medical condition in which patients display
the signs, symptoms, and abnormal
hormone levels seen in Cushing's
syndrome. Pseudo-Cushing's syndrome,
however, is not caused by a problem with
the hypothalamic-pituitary-adrenal axis as
Cushing's is. It is an idiopathic condition.
Diagnosis banding=Differential
diagnosis
Differentiation from Cushing's is extremely
difficult
Causes of Cushing's should be excluded with
imaging of the lungs, adrenal glands, and
pituitary gland - but these often appear normal in
Cushing's anyway
In the alcoholic patient with pseudo-Cushing's,
admission to hospital (and avoidance of alcohol)
will result in normal midnight cortisol levels within
5 days, excluding Cushing's[1]
Normal
Hyperplasia
Adenoma
Carcinoma
Kortisol
(g/dL,
AM/PM)
17/8
Normal
Normal
Normal
/ Normal
Normal
Normal
ACTH
(pg/mL)
10 - 80
20 - 90
Plasma
Urine
Kortisol
(g/24 h)
Sasaran terapi
Karena terjadi hiperkortisolisme maka
sasaran terapinya adl menurunkan kadar
kortisol plasma
TERAPI tergantung etiologi / penyebab
Terapi farmakologi obat
Terapi non farmakologitindakan bedah /
operasi dan radiasi
TERAPI
Treatment
Dosing
Etiology
Non drug
Drug
Initial
Usual
Max
Ectopic
ACTH
syndrome
Surgery
Chemotherapy
Irradiation
Metyrapone
tabs
250 mg
Aminoglutet
himide tabs,
250 mg
1 1, 5 g/d,
divided q4-6 h
1 6 g/d,
divided q46h
1 g/d,
divided q6
6 g/d
Cyproheptad
ine, 2 mg/5
mL syrup or
4 mg tabs
Mitotane
tabs 500 mg
4 mg bid
24 32
mg/d.,
divided qid
32 mg/d
Pituitary
dependent
Surgery
Irradiation
Metyrapone
Adrenal
adenoma
Surgery +
postoperative
replacement
Ketokonazole
, tabs 200
mg
0,5-1 g/d,
divided 96 bid
qid x 2
weeks
1-6 g/d,
increased by
1-2 g/d q3-7d
See above
200 mg qd bid
9 10 g/d,
divided tid
qid
See above
600 800
mg/d,
divided bid
2 g/d
16 g/d
See above
1200 mg/d
Terapi farmakologi
Steroid inhibitor
Adrenolitik agent
mitotan
Neuromodulator
agent
Antagonis reseptor
glukokortikoid
Steroid Inhibitor
Inhibitor steroid : metyrapone, aminogluthetimide,
ketokonazole
Metyrapone dan aminogluthetimide bila tdk kontinu,
mempunyai efikasi terbatas shg digunakan sesudah
operasi.
Metyrapone : menghambat aktivitas 11 hydroxylase,
sehingga sintesis kortisol terhambat.
Setelah terapi akan diikuti dg peningkatan kadar ACTH
plasma, karena tjd penurunan mendadak kortisol.
ES : mual, muntah, vertigo, sakit kepala, bingung, sakit
perut,
rash.
Ketokonazole
Antifungal derival imidazole
Mempunyai efektivitas tinggi menurunkan
kortisol
Mek kerja : menghambat enzim sit P450 (11
hydroxylase dan 17- hydroxylase)
ES : ginekomastia & penurunan kadar
testoterone plasma
ES umum : peningkatan transaminase hepatik
(reversibel), ginekomastia, gangguan GI
Aminoglutethimide
Pertama digunakan utk epilepsi, kmd sbg
inhibitor sintesis kortisol yg poten
Mek. Kerja : menghambat konversi
kolesterol mjd pregnenolon. Penurunan
kortisol plasma sampai dg 50%
ES : sedasi, mual, ataksia, dan skin rash.
Interaksi : dg warfarin akan menurunkan
efek antikoagulan.
Indikasi : penggunaan jangka pendek
Cushings disease dg sindrom ACTH ektopik,
digunakan sbg kombinasi dg metyrapone
efektif pd cushing yg tdk dpt dioperasi.
Neuromodulator agent
Cyproheptadine
Bromocriptine
Valproic acid
Octreotide
Cyproheptadine
Menurunkan sekresi ACTH
Perlu monitoring kadar kortisol pada urin
24 jam bebas kortisol
ES : sedasi & hiperfagia
Respon Rate (RR) tidak lebih 30%, jadi
perlu dipantau kekambuhannya
Tumor adrenal
Dg :
Pembedahan
adrenolectomy
Pada Primary
Pigmented
Micronodular Adrenal
Disease dan Carneys
Complex dg
pembedahan kel.
Adrenal.
Contd
4Be aware that surgery on the pituitary may cause ACTH levels to
fall below normal, which is typical. Therefore, it may become
necessary to follow up with administration of a synthetic form of
cortisol, such as hydrocortisone or prednisone.
5Expect that radiotherapy or a combination of radiation therapy and
medication may be necessary if you're not a good candidate for
surgery. While radiation works to shrink tumors, drugs such as
mitotane (Lysodren) help to inhibit cortisol production.
6Know that there are several medications used to control cortisone
secretion, including mitotane, aminoglutethimide, metyrapone,
trilostane and ketoconazole.
Read more: How to Treat Cushing's Syndrome | eHow.com
http://www.ehow.com/how_2048201_treat-cushings-syndrome.htm
l#ixzz12pFKoNXq
Monitoring terapi
Kadar kortisol serum pada pemeriksaan
urin 24 jam bebas kortisol
Perbaikan gejala & manifestasi klinik
Cushingsyndrome
Risiko kekambuhan terutama utk obat2 dg
RR yg rendah
Her weight at initial evaluation in our clinic at six months of age was 7.52kg
(6075th percentile) and length was 59.1cm (< 5th percentile). Blood
pressure was 110/70mmHg. Physical examination showed Cushingoid
facies, buffalo hump, facial acne, and poor muscle tone (Figure 2). There
were no signs of virilization. Family history was noncontributory.
Physical examination of the patient revealed features of Cushing Syndrome
including round facies, acne, plethora, central obesity, and poor muscle
tone; she lacked clitoromegaly, hirsutism or other signs of virilization.
An MRI of the abdomen showed a heterogeneous right adrenal mass
measuring 3.65.43.8cm; this mass was found to extend as a tumor
thrombus into the inferior vena cava. The tumor thrombus appeared to
extend to approximately 2cm from the right atrium. There were no
metastases seen in the liver or lungs on MRI. A Doppler ultrasound showed
minimal, but present flow around the IVC tumor thrombus which measured
2.50.91cm. Laboratory evaluation showed serum cortisol 70.8mcg/dl
(normal, 4.522.7mcg/dl); aldosterone 4.2ng/dl (normal 6.586.0ng/dl);
testosterone 59ng/dl (normal, 677ng/dl); ACTH <5 (normal, 1060pg/ml).