庫(kù)欣綜合征英文教學(xué)課件cushingsyndrome

1、Cushings Syndrome第1頁(yè)，共57頁(yè)。第2頁(yè)，共57頁(yè)。 第3頁(yè)，共57頁(yè)。Cushings syndrome is caused by chronic exposure to excess glucocorticoids (cortisol), characterized by truncal obesity, Round face, Plethora, Hirsutism, Violaceous striae, Hypertension, etc. Definition第4頁(yè)，共57頁(yè)。The hypothalamic-pituitary-adrenal axisfeedba

2、ck第5頁(yè)，共57頁(yè)。Cause of Cushings syndrome1. ACTH-dependent CortisolPituitary ACTHAdrenal hyperplasia Pituitary microadenomas(10mm) Cushings diseaseTumoursEctopic ACTH Lung small cell carcinoma, bronchial carcinoid tumoursEctopic ACTH syndrome第6頁(yè)，共57頁(yè)。2. ACTH-independent Tumor/HyperplasiaCortisolAutocrin

3、ePituitary ACTH Adrenal adenomaAdrenal carcinomaMicronodular adrenal hyperplasia (5mm)Cause of Cushings syndrome第7頁(yè)，共57頁(yè)。EpidemiologyCushings disease: Women:men=4:1Ectopic ACTH syndrome: Women:men=1:1Adrenocortical adenoma/carcinoma: Women:men=4:1第8頁(yè)，共57頁(yè)。Pathophysiology and Clinical Signs Metabolis

4、m (Glucose, Lipid, Protein) Immune system Blood system Reproductive system Central nervoussystem第9頁(yè)，共57頁(yè)。 1. Typical habitus Truncal obesity“Moon” face“Buffalo” humpViolaceous striaeBruisability OsteoporosisPlethoraPeculiar distributionof adipose tissueProtein catabolismRed blood cells第10頁(yè)，共57頁(yè)。Trun

5、cal obesity第11頁(yè)，共57頁(yè)。 Moon facePlethora第12頁(yè)，共57頁(yè)。Buffalo hump第13頁(yè)，共57頁(yè)。Violaceous striae第14頁(yè)，共57頁(yè)。Violaceous striae第15頁(yè)，共57頁(yè)。 Osteoporosis：vertebral bodies flatten 第16頁(yè)，共57頁(yè)。 2. Hypertension, Electrolyte disturbancesWaterandsodiumretention, potassium depletionHypertension, Hypokalemialeft ventricula

6、r hypertrophy, heart failure, cerebrovascular accident, etc.第17頁(yè)，共57頁(yè)。3. Impaired glucose tolerance, Diabetes mellitus (Steroid diabetes)Stimulation ofhepatic gluconeogenesis，resistance of insulin第18頁(yè)，共57頁(yè)。4. InfectiousInfections of Bacteria, Fungi, VirusesImmunosuppression: functions and numbers of

7、 neutrophils, lymphocytes, monocytes,macrophages theanatomical barrierfunction of the skin第19頁(yè)，共57頁(yè)。5. Sexualdysfunctionwomen -Amenorrhea or Oligomenorrhea -Virilization: Hirsutism, Acne, MastatrophyInhibition of Gonadotropin, Adrenal androgensmen-Decreased libido第20頁(yè)，共57頁(yè)。Neurologic changes: decrea

8、sed strength, headaches, decreased memory and cognitionPsychiatric changes: depression, anxiety, irritabilityHyperpigmentation: Ectopic ACTH syndrome and severe Cushings disease6. Others第21頁(yè)，共57頁(yè)。MSH(Melanocyte-stimulating hormone)Melanocyte MelaninPigment黑色素細(xì)胞黑色素Mechanism of hyperpigmentation第22頁(yè)，共

9、57頁(yè)。ACTHThe partial action of MSHMelanin pigment depositionHyperpigmentation第23頁(yè)，共57頁(yè)。4. ManifestationHyperpigmentation: 第24頁(yè)，共57頁(yè)。TestsPlasma cortisol levels 24-hour Urine free cortisol (UFC) 第25頁(yè)，共57頁(yè)。3. Plasma ACTHDiscrimination of ACTH-dependent and -independent Cushings syndromeCushings disease

10、Ectopic ACTH-syndromeAdrenal adenoma第26頁(yè)，共57頁(yè)。 4. Plasma cortisol circadian rhythmNormal cortisol circadian rhythm第27頁(yè)，共57頁(yè)。Plasma cortisol circadian rhythm of cushings syndromeNormal 24h 08h 16hCushings syndrome24h 08h 16h第28頁(yè)，共57頁(yè)。5. Dynamic tests1 mg overnight dexamethasone suppression test (1mg

11、DST)Method: 1 mg by mouth, between 23h and 0h, and the measurement of cortisol between 8h and 9h the following morning.Results: Normal: Cortisol50nmol/L 第29頁(yè)，共57頁(yè)。Low-dose dexamethasone suppression test (LDDST) Result Normal: Day 3 plasma cortisol 50nmol/LMethod (2mg/day)0800h1600h0000hDay 1Dexa0.75

12、mg0.75mg0.5mgDay 2Dexa0.75mg0.75mg0.5mg0700h keep 24-hour urineDay 30800h measure plasma cortisol and 24-hour urine cortisol第30頁(yè)，共57頁(yè)。0800h1400h2000h0200hDay 10700h keep 24h urine, measure plasma cortisolDay 2Dexa3 tablets3 tablets3 tablets2 tabletsDay 3Dexa3 tablets3 tablets3 tablets2 tablets0700h

13、keep 24h urine Day 40800h measure plasma cortisol and 24h urine cortisolMethod (8mg/day)Result Be suppressed: Day 4 plasma cortisol 50% of the basal levelHigh-dose dexamethasone suppression test (HDDST)第31頁(yè)，共57頁(yè)。Discrimination of the causes of Cushings syndrome by HDDST HDDSTACTHCushings diseasesupp

14、ressedAdrenal adenoma/carcinomaNo Ectopic ACTH syndromeNo 第32頁(yè)，共57頁(yè)。Pituitary MRI：microadenomaPituitary MRI：macroadenoma6. Imaging examination第33頁(yè)，共57頁(yè)。CT：normal adrenal CT：adrenal adenoma第34頁(yè)，共57頁(yè)。7. Inferior petrosal sinus sampling (BIPSS)Discrimination of Cushings disease and Ectopic ACTH syndrom

15、eInvasive Test第35頁(yè)，共57頁(yè)。Cushings syndrome (CS) suspected24hUFC, Plasma cortisol circadian rhythm, 1mg DSTNormalAbnormalLow-dose DSTCS excludedCS confirmedAbnormalDiagnosis1. Step第36頁(yè)，共57頁(yè)。2. Etiologic diagnosisPlasma ACTHHigh-dose DST3. Location diagnosisPituitary enhanced MRIAdrenal enhanced CTChes

16、t enhanced CT/Whole body PET-CT第37頁(yè)，共57頁(yè)。Cushings diseaseACTHSuppressed by High-dose DSTPituitary lesions by CT, MRIBilateral adrenal mild hyperplasia4. Differential diagnosis第38頁(yè)，共57頁(yè)。Ectopic ACTH syndromePlasma ACTHHypokalaemia, HyperpigmentationNot suppressed by high-dose DSTChest CT/Whole body P

17、ET-CT第39頁(yè)，共57頁(yè)。Adrenal adenoma /carcinomaAdenoma：progressed graduallyCarcinoma：progressedrapidly ，evident sign of androgenexcess (virilization)Plasma ACTHNot suppressed by high-dose DSTAdrenal enhanced CT第40頁(yè)，共57頁(yè)。Surgical treatment Transsphenoidal microsurgery：most widely usedPituitary irradiation

18、post operationHypophysectomy Total adrenalectomyCushings diseaseTreatment第41頁(yè)，共57頁(yè)。Adrenal neoplasmaLaparoscopic adrenalectomy 第42頁(yè)，共57頁(yè)。 Hypopituitarism / hypoadrenocorticism -Glucocorticoid and mineralocorticoid replacement Nelsons syndrome: rapid pituitary tumor enlargement and increased pigmenta

19、tion secondary to high ACTH levels after total adrenalectomy due toCushings disease -Periodic pituitary MRI and ACTH measurement -Pituitary irradiation Adverse effects 第43頁(yè)，共57頁(yè)。Medical TherapySteroidogenesis inhibitors: Suppression of cortisol productionKetoconazole MetyraponeMitotaneEtomidate第44頁(yè)，

20、共57頁(yè)。Case one第45頁(yè)，共57頁(yè)。Female，30-year，Postpartum depression for 6 months，weight gain for 3 months.Physical examination：T36.5C, BP164/116mmHg, Round face, Plethora, bearded jaw, hirsute back, wide violaceous strae, distended abdomen.Tests：-24h UFC 1620.9nmmol -Plasma cortisol circadian rhythm: 8 am 7

21、54.7nmmol/L 16 pm 647.0 nmmol/L 0 am 671.9 nmmol/L -ACTH (8am) 1718.76nmmol/L High-dose DST Plasma cortisol 643.35nmmol/L Urine cortisol 2406.2nmmol/L Not suppressed by both Low-dose and high dose DST第47頁(yè)，共57頁(yè)。Adrenal CT第48頁(yè)，共57頁(yè)。Diagnosis？Cushings syndromeAdrenal adenoma 第49頁(yè)，共57頁(yè)。Treatment Adrenalectomy第50頁(yè)，共57頁(yè)。Case Two第51頁(yè)，共57頁(yè)。Male，15-year，Growthretardation for 8 years，fatigue and weight gain for 3 months.Physical examination：T36.7C， BP126/96mmHg, “Moon” face, “Buffalo” hump, Violaceous striae on bilateral inner thighs. A 2x2cm nodule was touched in thyroid