Download 投影片 1

門診處方討論
藥 師 鄭 育 凌
1
2
病史
• This p’t is 38 y/o female,在95年 1/31看診新陳代謝科
• 診斷:庫興氏症候群、 高血壓、 失眠
• 檢查:血液中cortisol濃度偏高,且收集24小時尿液 ,可
測得cortisol值遠大於正常人。做腦部CT-scan
發現病患在腦下垂體有corticotropic adenoma故
給予ketoconazole 1# TID治療
3
Introduction :
Cushing's syndrome is a hormonal disorder caused by
prolonged exposure of the body's tissues to high
levels of the hormone cortisol. Sometimes called
"hypercortisolism“
1.
•
•
•
•
2.
•
•
•
Causes: 主要分成2種
ACTH independent— exogenous
iatrogenic: administration of corticosteroids
Adrenal adenoma
Micronodular hyperplasia
Macronodular hyperplasia
ACTH dependent— endogenous
Pituitary ACTH-secreting adenoma
Ectopic ACTH
Ectopic CRH
4
•
•
•
•
•
•
•
•
•
•
•
Signs and symptoms
moon facies, facial plethora
supraclavicular fat pads
buffalo hump
truncal obesity
purple striae
proximal muscle weakness
easy bruising
weight gain, hirsutism
in children, growth
retardation
Hypertension, osteopenia,
diabetes mellitus
impaired immune function
may occur.
5
Fig1
Pathophysiology of Cushing's Disease
6
Fig2
7
Fig3
8
Fig4
9
Differential Diagnosis
 篩檢:
plasma cortisol
24-Hour Urinary Free Cortisol Level:＞100µg/dl/24hr
 診斷:
low-dose dexamethasone suppression test(LDDST):
11pm dexamethasone 1mg, serum cortisol >10µg/dl
 鑑別
high-dose dexamethasone suppression test:
dexamethasone 2mg q6h 連續48小時
血漿中的ACTH濃度:
CRH Stimulation Test
17-hydroxycorticosteroid、17-ketosteroid(17-KS)、
testosetrone、estradiol。
10
造影 : x-rays, CT scan, MRI
Treatment
Reducing corticosteroid use
Surgery: transsphenoidal surgery, adrenalectomy
Radiation therapy
• Hormone replacement
→may require glucocorticoid replacement to avoid
adrenal insufficiency
Medical therapy:主要分四大類
11
Drug therapy
Synthesis inhibitors & glucocorticoid antagonists
一.Adrenal enzyme inhibitors:
Ketoconazole(NizoralR) :
 is the most popular and effective of these agents for
long-term use and usually is the agent of choice
 Dosage:200-400mg PO bid/tid
 Mechanism of action:
Imidazole broad-spectrum antifungal agent that acts
on several of the P450 enzymes, including the first
step in cortisol synthesis, cholesterol side-chain
cleavage, and conversion of 11-deoxycortisol to cortisol.
12
Adverse effects:
headache,sedation,nausea,irregular menses,
decreased libido, impotence, gynecomastia,and
elevated liver function
 Precaution:
avoided administer antacid,anticholinergics, or H2
blockers at least 2h after taking ketoconazole
Metyrapone
 Dosage:1 g/d PO divided qid; increase gradually
, not to exceed 4.5 g/d
 blocks 11-ß-hydroxylase activity,the final step in
cortisol synthesis.
13
Aminoglutethimide(Cytadren),
 Dosage:250 mg PO bid initially; increase to 2 g qid
 inhibits the synthesis of cortisol, aldosterone and sex
hormones
 Adverse effects :
somnolence, headache, a generalized pruritic rash,
hypothyroidism, and goiter. In rare cases, it may
cause bone marrow suppression
Trilostane
 Dosage:200-1000mg/day
 inhibits3ß-hydroxysteroid dehydrogenase
 It is not a first-choice agent because it is a weak
inhibitor of steroidogenesis
14
Etomidate
 imidazole-derivative anesthetic agent
 block 11ß- hydroxylase
 use is limited by the intravenous route: 0.3 mg/kg/h
二.Glucocorticoid blocking agents
Mifepristone (RU486)
 Dosage:20mg/kg/day
 antiprogestational agent, anti-glucocorticoid effects.
 an investigational basis for treatment of Cushing
syndrome
15
三. Centrally active drugs
include bromocriptine, cyproheptadine, valproic acid,
and octreotide.
 decrease CRH or ACTH release
 Currently, use of these agents is investigational
四.adrenolytic agent
Mitotane(o,p’-DDD ,LysodrenR)
 inhibiting 11ß-hydroxylase and cholesterol side-chain
cleavage enzymes.
 This drug also leads to mitochondrial destruction
and necrosis of adrenocortical cells in the zona
fasciculata and reticularis
 Is expensive and is limited by adverse
gastrointestinal and neurologic effects, including nausea,
diarrhea, dizziness, and ataxia
16
Reference
• Ilias I, Torpy DJ, Pacak K, et al: Cushing's syndrome due to
ectopic corticotropin secretion: twenty years' experience at the
National Institutes of Health. J Clin Endocrinol Metab 2005 Aug;
90(8): 4955-62[Medline].
• Mark S.Cooper etc. NEJM 2003;348:727-34
• Wiebke Arlt etc. Lancet 2003; 361: 1881-93
• DIAGNOSTIC TESTING FOR CUSHING'S SYNDROME
By Dr. James Findling, December, 2003
• Cushing's Disease Clinical Manifestations and Diagnostic
Evaluation-september 1,2000-American family physician
• Adapted with permission from Orth DN. Cushing's syndrome. N
Engl J Med 1995;332:791-803 [Published erratum appears in N
Engl J Med 1995; 332:1527].
17