医学精品课件：（参考翻译）01.2cushing syndrome 2017.ppt

1、Cushings Syndrome库兴综合征GE QianThe First Affiliated Hospital of Chongqing Medical UniversityDepartment of Endocrinology Cushings syndrome is caused by chronic exposure to excess glucocorticoids(cortisol 皮皮质醇质醇),characterized by truncal obesity 向心性肥向心性肥胖胖,Round face 满月脸满月脸,Plethora 多血症多血症,Hirsutism 多毛症

2、多毛症,Violaceous striae 紫色条纹紫色条纹（？）（？）,Hypertension 高血压高血压,etc.DefinitionThe hypothalamic 下丘脑-pituitary 垂体-adrenal 肾上腺 axisfeedbackCause of Cushings syndrome1.ACTH-dependent CortisolPituitary ACTHAdrenal hyperplasia肾上腺增生肾上腺增生 Pituitary microadenomas 垂体微腺瘤(10mm)Cushings diseaseTumoursEctopic 异常的异常的 ACT

3、H Lung small cell carcinoma,bronchial carcinoid tumours 支气管类癌肿瘤Ectopic ACTH syndrome2.ACTH-independent Tumor/HyperplasiaCortisolAutocrine自分泌自分泌Pituitary ACTH Adrenal adenoma 肾上腺瘤Adrenal carcinoma 肾上腺癌Micronodular adrenal hyperplasia 小结节型肾上腺皮质增生症(5mm)Cause of Cushings syndromeEpidemiologyCushings dis

4、ease:Women:men=4:1Ectopic ACTH syndrome:Women:men=1:1Adrenocortical 肾上腺皮质肾上腺皮质 adenoma/carcinoma:Women:men=4:1Pathophysiology and Clinical Signs Metabolism(Glucose,Lipid,Protein)Immune system Blood system Reproductive system 生殖系统 Central nervous system1.Typical habitus 典型状态 Truncal obesity“Moon”face

5、“Buffalo”hump 水牛背Violaceous striaeBruisability 易淤血Osteoporosis 骨质疏松Plethora 多血症Peculiar distributionof adipose tissue 脂脂肪组织特殊分布肪组织特殊分布Protein catabolism 分解代谢分解代谢Red blood cellsTruncal obesity Moon facePlethoraBuffalo humpViolaceous striaeViolaceous striae Osteoporosis：vertebral bodies flatten 椎体变平 2

6、.Hypertension,Electrolyte disturbances 电解质紊乱 Water and sodium retention,potassium depletion水钠潴留，钾丢失Hypertension,Hypokalemia 低钾血症left ventricular hypertrophy 左室肥大,heart failure,cerebrovascular accident 脑血管意外,etc.3.Impaired glucose tolerance 糖耐量降低,Diabetes mellitus(Steroid diabetes 类固醇糖尿病)Stimulation

7、of hepatic gluconeogenesis 刺激肝糖异生，resistance of insulin 胰岛素抵抗4.InfectiousInfections of Bacteria,Fungi,VirusesImmunosuppression 免疫抑制:functions and numbers of neutrophils 中性粒细胞,lymphocytes,monocytes 单核细胞,macrophages 巨噬细胞 the anatomical 解剖的 barrier function of the skin5.Sexual dysfunction 性功能障碍women -A

8、menorrhea 闭经 or Oligomenorrhea 月经过少 -Virilization 男性化:Hirsutism多毛,Acne 痤疮,Mastatrophy 乳腺萎缩Inhibition of Gonadotropin 促性腺激素,Adrenal androgens 肾上腺雄激素men-Decreased libido 性欲减退Neurologic changes:decreased strength,headaches,decreased memory and cognition 认知Psychiatric changes:depression,anxiety,irritabi

9、lity 易怒Hyperpigmentation 色素沉着过度:Ectopic ACTH syndrome and severe Cushings disease6.OthersMSH(Melanocyte-stimulating hormone)Melanocyte MelaninPigment黑色素细胞黑色素细胞黑色素黑色素Mechanism of hyperpigmentationACTHThe partial action 部分作用部分作用 of MSHMelanin pigment deposition 黑色素沉积黑色素沉积Hyperpigmentation 色素沉着过度色素沉着过度

10、4.Manifestationp Hyperpigmentation:Tests1.Plasma cortisol levels 2.24-hour Urine free cortisol(UFC)3.Plasma ACTHDiscrimination 区别区别 of ACTH-dependent and-independent Cushings syndromeCushings diseaseEctopic ACTH-syndromeAdrenal adenoma 4.Plasma cortisol circadian rhythm 血浆皮质醇昼夜节律Normal cortisol circ

11、adian rhythmPlasma cortisol circadian rhythm of cushings syndromeNormal Cushings syndrome5.Dynamic tests1 mg overnight 过夜 dexamethasone 地塞米松 suppression test(1mg DST)Method:1 mg by mouth,between 23h and 0h,and the measurement of cortisol between 8h and 9h the following morning.Results:Normal:Cortiso

12、l50nmol/L Low-dose dexamethasone suppression test(LDDST)Result Normal:Day 3 plasma cortisol 50nmol/L Method(2mg/day)0800h1600h0000hDay 1 Dexa0.75mg0.75mg0.5mgDay 2Dexa0.75mg0.75mg0.5mg0700h keep 24-hour urineDay 3 0800h measure plasma cortisol and 24-hour urine cortisol 0800h1400h2000h0200hDay 10700

13、h keep 24h urine,measure plasma cortisolDay 2Dexa3 tablets3 tablets3 tablets2 tabletsDay 3Dexa3 tablets3 tablets3 tablets2 tablets0700h keep 24h urine Day 40800h measure plasma cortisol and 24h urine cortisol Method(8mg/day)Result Be suppressed:Day 4 plasma cortisol 50%of the basal levelHigh-dose de

14、xamethasone suppression test(HDDST)Discrimination of the causes of Cushings syndrome by HDDST 大大剂量地塞米松抑制试剂量地塞米松抑制试验验 HDDSTACTHCushings diseasesuppressedAdrenal adenoma/carcinomaNo Ectopic ACTH syndromeNo Pituitary MRI：microadenomaPituitary MRI：macroadenoma6.Imaging examinationCT：normal adrenal CT：ad

15、renal adenoma7.Inferior petrosal sinus sampling 双侧岩下窦静脉取血(BIPSS)Discrimination of Cushings disease and Ectopic ACTH syndromeInvasive TestCushings syndrome(CS)suspected24hUFC,Plasma cortisol circadian rhythm,1mg DSTNormalAbnormalLow-dose DSTCS excludedCS confirmedAbnormalDiagnosis1.Step2.Etiologic di

16、agnosisPlasma ACTHHigh-dose DST3.Location diagnosisPituitary enhanced MRIAdrenal enhanced CTChest enhanced CT/Whole body PET-CTCushings disease ACTH Suppressed by High-dose DST Pituitary lesions by CT,MRI Bilateral adrenal mild hyperplasia4.Differential diagnosisEctopic ACTH syndrome Plasma ACTH Hyp

17、okalaemia 低钾血症,Hyperpigmentation Not suppressed by high-dose DST Chest CT/Whole body PET-CTAdrenal adenoma/carcinoma Adenoma：progressed gradually Carcinoma：progressed rapidly，evident sign of androgen 雄激素 excess(virilization 男性化)Plasma ACTH Not suppressed by high-dose DST Adrenal enhanced CTSurgical

18、treatment Transsphenoidal microsurgery 经蝶骨显微手术：经蝶骨显微手术：most widely usedPituitary irradiation 照射照射 post operationHypophysectomy 垂体切除术垂体切除术Total adrenalectomy 全肾上腺切除术全肾上腺切除术Cushings diseaseTreatmentAdrenal neoplasma 赘生物Laparoscopic adrenalectomy 腹腔镜下肾上腺切除术腹腔镜下肾上腺切除术 Hypopituitarism 垂体机能减退垂体机能减退/hypoad

19、renocorticism 肾上腺皮质功能肾上腺皮质功能减退减退 -Glucocorticoid and mineralocorticoid 盐皮质激素 replacement Nelsons syndrome:rapid pituitary tumor enlargement and increased pigmentation secondary to high ACTH levels after total adrenalectomy due to Cushings disease -Periodic pituitary MRI and ACTH measurement -Pituita

20、ry irradiation Adverse effects Medical TherapySteroidogenesis inhibitors 类固醇合成抑制剂类固醇合成抑制剂:Suppression of cortisol productionKetoconazole 酮康唑酮康唑 Metyrapone 美替拉酮美替拉酮Mitotane 米托坦米托坦Etomidate 依托咪酯依托咪酯Case oneFemale，30-year，Postpartum depression 产后抑郁产后抑郁 for 6 months，weight gain for 3 months.Physical exa

21、mination：T36.5C,BP164/116mmHg,Round face,Plethora,bearded jaw 下颌有胡须,hirsute back,wide violaceous strae,distended abdomen.Tests：-24h UFC 1620.9nmmol -Plasma cortisol circadian rhythm:8 am 754.7nmmol/L 16 pm 647.0 nmmol/L 0 am 671.9 nmmol/L -ACTH(8am)1718.76nmmol/L High-dose DST Plasma cortisol 643.35

22、nmmol/L Urine cortisol 2406.2nmmol/L Not suppressed by both Low-dose and high dose DSTAdrenal CTDiagnosis？Cushings syndromeAdrenal adenoma Treatment AdrenalectomyCase TwoMale，15-year，Growth retardation 生长迟滞生长迟滞 for 8 years，fatigue and weight gain for 3 months.Physical examination：T36.7C，BP126/96mmHg

23、,“Moon”face,“Buffalo”hump,Violaceous striae on bilateral inner thighs 大腿内侧.A 2x2cm nodule was touched in thyroid gland,without tenderness,with clear border.Tests：K+3.0mmol/L，Fast plasma glucose(FPG)8.0mmol/L，24h UFC758ug Plasma cortisol circadian rhythm:8 am 1379nmmol/L 16 pm 1379nmmol/L 0 am 1379nm

24、mol/L ACTH(8am)246pg/mL History Dynamic Tests：-Not suppressed by LDDST and HDDST -Thyroid function：TSH 19.8 IU/ml -Calcitonin 243ng/L -Pituitary MRI：Normal -Adrenal CT：Bilateral adrenal hyperplasia -X-ray：Osteoporosis in spine 脊柱 and pelvis 骨盆 -Cervical CT:Thyroid nodule Diagnosis？Medullary thyroid carcinoma Ectopic ACTH syndromeCushings syndromeTreatmentTotal thyroidectomy Harrisons Internal Medicine 17th Edition Harrisons Endocrinology 3rd EditionReference BookThank you