医学专题一Cushing综合症.ppt

《医学专题一Cushing综合症.ppt》由会员分享，可在线阅读，更多相关《医学专题一Cushing综合症.ppt（70页珍藏版）》请在淘文阁 - 分享文档赚钱的网站上搜索。

1、Cushing syndromeCushing syndromeCushing 综合症第一页，共七十页。第二页，共七十页。DefinitionDefinition Cushing syndrome,the Cushing syndrome,the constellation of clinical signs constellation of clinical signs and symptoms resulting form and symptoms resulting form chronic glucocorticoid excess,was chronic glucocorticoid

2、 excess,was probably first described in 1899 probably first described in 1899 第三页，共七十页。定定 义义为各种病因造成肾上腺分泌过多的糖为各种病因造成肾上腺分泌过多的糖皮质激素（主要是皮质醇）所致病症皮质激素（主要是皮质醇）所致病症(bngzhng)(bngzhng)的总称的总称主要临床表现为满月脸，多血质外貌，主要临床表现为满月脸，多血质外貌，向心性肥胖、痤疮、皮肤紫纹高血压向心性肥胖、痤疮、皮肤紫纹高血压和骨质疏松等和骨质疏松等第四页，共七十页。第五页，共七十页。第六页，共七十页。Aetiology Aetio

3、logy Clinical presentationClinical presentationlaboratory examinationlaboratory examination Diagnosis and differential Diagnosis and differential diagnosisdiagnosisTreatment (principle)Treatment (principle)PrognosisPrognosis 第七页，共七十页。病因分类病因分类临床表现临床表现实验室检查实验室检查诊断诊断(zhndun)(zhndun)及鉴别诊及鉴别诊断断(zhndun)(z

4、hndun)治疗治疗(原则原则)预后预后第八页，共七十页。AetiologyAetiology病因病因(bngyn)(bngyn)分类分类第九页，共七十页。HypothalamusHypothalamus 下丘脑下丘脑（CRHCRH）pituitary glandpituitary gland 垂体垂体(chut)(chut)（ACTHACTH）adrenal cortexadrenal cortex肾上腺皮质肾上腺皮质zona glomerulosa zona fasciculatazona glomerulosa zona fasciculata zona zona reticularis

5、reticularis（AldosteroneAldosterone）（）（cortisolcortisol）（）（gonadal hormonegonadal hormone）+-第十页，共七十页。AetiologyAetiologyACTH-dependent Cushing syndromeACTH-dependent Cushing syndromeCushing diseaseCushing diseaseEctopic ACTH syndromeEctopic ACTH syndrome ACTH-independent Cushing syndrome ACTH-independ

6、ent Cushing syndrome Adrenocortical adenomaAdrenocortical adenomaAdrenocortical adenocarcinomaAdrenocortical adenocarcinomaMicronodular adrenal diseaseMicronodular adrenal diseaseMassive macronodular adrenal diseaseMassive macronodular adrenal disease第十一页，共七十页。病因病因(bngyn)(bngyn)分类分类 依赖依赖ACTH ACTH 的的

7、cushingcushing综合症综合症 cushing cushing 病病异位异位ACTHACTH综合症综合症非依赖非依赖ACTH ACTH 的的cushingcushing综合症综合症肾上腺皮质腺瘤肾上腺皮质腺瘤 肾上腺皮质癌肾上腺皮质癌 原发性色素原发性色素(s s)(s s)结节性肾上腺病结节性肾上腺病大结节性巨大肾上腺病大结节性巨大肾上腺病第十二页，共七十页。Clinical Clinical featurefeature各型临床各型临床(ln chun)(ln chun)特征特征第十三页，共七十页。Cushing DiseaseCushing DiseaseIt is the m

8、ost common type of Cushing syndrome,and accounts It is the most common type of Cushing syndrome,and accounts for about 70%of the syndromefor about 70%of the syndromePathogenesisPathogenesisMost patients have ACTH-secreting anterior pituitary Most patients have ACTH-secreting anterior pituitary corti

9、cortrope microadenomas(corticortrope microadenomas(10mm in diameter),but a small 10mm in diameter),but a small number have diffuse corticotrope hyperplasia and pituitary number have diffuse corticotrope hyperplasia and pituitary macroadenomamacroadenoma第十四页，共七十页。CushingCushing病病最常见，约占最常见，约占cushingcu

10、shing综合症的综合症的70%70%,多见于成多见于成人，女性多于男性，是由于垂体分泌过多的人，女性多于男性，是由于垂体分泌过多的ACTHACTH所致所致病因病因垂体微腺瘤垂体微腺瘤80%80%垂体大腺瘤垂体大腺瘤1010：压迫、侵袭等症状：压迫、侵袭等症状(zhngzhung)(zhngzhung)下丘脑功能紊乱下丘脑功能紊乱第十五页，共七十页。Ectopic ACTH syndromeEctopic ACTH syndromeThe majority of patients with ectopic ACTH syndrome have The majority of patients

11、with ectopic ACTH syndrome have outside pituitary tumor outside pituitary tumor Other sites are pulmonary carcinosis,carcinoid of Other sites are pulmonary carcinosis,carcinoid of bronchus,thymic carcinoma pancreatic cancer,bronchus,thymic carcinoma pancreatic cancer,chromaffin tumor,medullary carci

12、noma of thyroid and chromaffin tumor,medullary carcinoma of thyroid and so onso on 第十六页，共七十页。异位异位(y wi)(y wi)ACTHACTH综合症综合症继发于垂体以外的恶性肿瘤继发于垂体以外的恶性肿瘤小细胞肺癌小细胞肺癌(fi i)(fi i)、支气管类癌、胸腺癌、胰、支气管类癌、胸腺癌、胰腺癌、嗜铬细胞瘤、神经母细胞瘤腺癌、嗜铬细胞瘤、神经母细胞瘤 等等等等临床上分两型临床上分两型缓慢进展型缓慢进展型迅速进展型迅速进展型第十七页，共七十页。Adrenocortical adenomaAdrenoco

13、rtical adenomaPatients with adrenal adenoma usually have gradual Patients with adrenal adenoma usually have gradual onset of sign of hypercortisolism,accounts for onset of sign of hypercortisolism,accounts for about 15-20%of the syndromeabout 15-20%of the syndromeAdenoma is round or ellipse,diameter

14、 is 3-4cm,weight is Adenoma is round or ellipse,diameter is 3-4cm,weight is about 40gabout 40g第十八页，共七十页。肾上腺皮质肾上腺皮质(pzh)(pzh)腺瘤腺瘤多见于成人，男性多见于成人，男性(nnxng)(nnxng)多于女性多于女性 15%-20%15%-20%腺瘤呈圆形或椭圆形，直径约腺瘤呈圆形或椭圆形，直径约3-43-4cmcm，重重4040g g左右，包膜完整左右，包膜完整其病缓慢，病情中等，多毛及雄激素增多少见其病缓慢，病情中等，多毛及雄激素增多少见第十九页，共七十页。Adrenocor

15、tical adenocarcinomaAdrenocortical adenocarcinomaIt occurs in lower than 5%patients of It occurs in lower than 5%patients of cushing syndromecushing syndromePatients with adenocarcinoma tend to Patients with adenocarcinoma tend to have a more acute and progressive course have a more acute and progre

16、ssive course and virilizing effects may predominateand virilizing effects may predominateThe bulk of tumor is largerThe bulk of tumor is larger第二十页，共七十页。肾上腺皮质肾上腺皮质(pzh)(pzh)腺癌腺癌占占cushingcushing综合症的综合症的5 5以下以下瘤体积大（直径瘤体积大（直径5-65-6cm)cm)，肿瘤可浸润肿瘤可浸润(jnrn)(jnrn)包膜包膜病情重，进展快，重度病情重，进展快，重度cushingcushing综合症的表

17、现综合症的表现(低钾性碱中毒、女性低钾性碱中毒、女性男性化）男性化）第二十一页，共七十页。Micronodular adrenal Micronodular adrenal diseasediseaseThe disease is also known as Meadors syndrome The disease is also known as Meadors syndrome About half of patients with this disorder have no About half of patients with this disorder have no distinc

18、tive clinical presentation other than being distinctive clinical presentation other than being young-always younger than 30 years of age,half younger young-always younger than 30 years of age,half younger than 15 years and some infantsthan 15 years and some infants第二十二页，共七十页。原发性色素原发性色素(s s)(s s)结节性肾

19、上腺病结节性肾上腺病此病又称这为此病又称这为MeadorMeador综合症或原发性色素综合症或原发性色素 性结节性肾上腺疾性结节性肾上腺疾病病患者多为儿童和青少年患者多为儿童和青少年临床表现：一部分同一临床表现：一部分同一(tngy)(tngy)般的临床表现般的临床表现 一部分为家族性，呈显性遗传一部分为家族性，呈显性遗传 (Carney(Carney综综合症）合症）第二十三页，共七十页。Massive macronodular adrenal diseaseMassive macronodular adrenal disease大结节性巨大大结节性巨大(jd)(jd)肾上腺病肾上腺病第二十四

20、页，共七十页。Clinical Clinical presentationpresentation临床表现临床表现第二十五页，共七十页。典型病例典型病例(bngl)(bngl)重型重型cushingcushing综合症综合症早期病例早期病例以并发症为主者以并发症为主者周期性或间歇性周期性或间歇性 第二十六页，共七十页。Typical casesTypical cases典典 型型 病病 例例第二十七页，共七十页。Clinical presentation1Clinical presentation1Progressive obesity is the most common sign.It i

21、s Progressive obesity is the most common sign.It is usually central,involving the face,neck trunk and usually central,involving the face,neck trunk and abdomenabdomenAll over the body and nervous system:weakness,change of All over the body and nervous system:weakness,change of emotion and so onemoti

22、on and so onThe skin is atrophic,the stratum corneum is The skin is atrophic,the stratum corneum is thinned,and there is loss of subcutaneous fat thinned,and there is loss of subcutaneous fat allowing subcutaneous blood vessels to been seenallowing subcutaneous blood vessels to been seen第二十八页，共七十页。C

23、linical presentation2Clinical presentation2Cardiovascular complication is a major cause of Cardiovascular complication is a major cause of morbidity and death in untreated Cushing syndromemorbidity and death in untreated Cushing syndrome Moderate hypertension is common Moderate hypertension is commo

24、nGlucocorticoid suppress immune functionGlucocorticoid suppress immune functionInflammatory and febrile responses to bacterial Inflammatory and febrile responses to bacterial infection are suppressedinfection are suppressedDysbolism and sexual disturbance sometimes occurDysbolism and sexual disturba

25、nce sometimes occur第二十九页，共七十页。临床表现临床表现1 1满月脸、多血质外貌满月脸、多血质外貌(wimo)(wimo)、向心性肥胖、向心性肥胖第三十页，共七十页。第三十一页，共七十页。临床表现临床表现2 2全身和神经系统症状：肌无力，常有不同程度的精神、情绪变化全身和神经系统症状：肌无力，常有不同程度的精神、情绪变化皮肤表现皮肤表现(bioxin)(bioxin)：皮肤薄，微血管脆性增加，易出现淤斑、紫：皮肤薄，微血管脆性增加，易出现淤斑、紫纹纹,易合并真菌感染易合并真菌感染,有时可出现皮肤色素沉着有时可出现皮肤色素沉着第三十二页，共七十页。第三十三页，共七十页。第三十

26、四页，共七十页。临床表现临床表现2 2心血管表现：心血管表现：高血压心衰、脑血管意外高血压心衰、脑血管意外凝血功能异常凝血功能异常(血小板，纤维蛋白原血小板，纤维蛋白原 ），脂代谢紊乱，动静脉血栓），脂代谢紊乱，动静脉血栓对感染的抵抗力减弱对感染的抵抗力减弱使达到炎症病灶的单核细胞减少使达到炎症病灶的单核细胞减少巨噬细胞对抗原的固定、吞噬和杀伤力减弱巨噬细胞对抗原的固定、吞噬和杀伤力减弱中性粒细胞运动能力，吞噬作用减弱中性粒细胞运动能力，吞噬作用减弱抗体抗体(kngt)(kngt)的形成受到阻抑的形成受到阻抑第三十五页，共七十页。临床表现临床表现3 3性功能障碍：性功能障碍：月经减少、不规则、

27、停经、痤疮等月经减少、不规则、停经、痤疮等明显明显(mngxin)(mngxin)男性化（警惕肾上腺癌）男性化（警惕肾上腺癌）代谢障碍：代谢障碍：脂、蛋白、糖代谢脂、蛋白、糖代谢低钾性碱中毒低钾性碱中毒 ，低钙，低钙 骨质疏松，伤口愈合不良，生长发育延迟骨质疏松，伤口愈合不良，生长发育延迟第三十六页，共七十页。重型重型(zhngxng)(zhngxng)cushingcushing综合症综合症多由癌肿所致多由癌肿所致(su zh)(su zh)，病情严重，进展，病情严重，进展迅速迅速体重减轻体重减轻高血压、浮肿、低钾性碱中毒高血压、浮肿、低钾性碱中毒第三十七页，共七十页。早期早期(zoq)(z

28、oq)病例病例全身情况全身情况(qngkung)(qngkung)较好较好以高血压为主以高血压为主肥胖、向心性的特点不够显著肥胖、向心性的特点不够显著第三十八页，共七十页。以并发症为主者以并发症为主者CushingCushing综合症本身不明显综合症本身不明显多以并发症就诊：心衰、脑卒中病多以并发症就诊：心衰、脑卒中病理性骨折、精神症状、肺部感染理性骨折、精神症状、肺部感染(gnrn)(gnrn)等等等等第三十九页，共七十页。周期性或间歇性周期性或间歇性第四十页，共七十页。Laboratory examinationLaboratory examination实验室检查实验室检查(jinch)

29、(jinch)第四十一页，共七十页。Laboratory examinationLaboratory examination The laboratory examination of Cushing syndrome is The laboratory examination of Cushing syndrome is cortisol hypersecretion.cortisol hypersecretion.Increased urinary excretion of cortisol and urinary Increased urinary excretion of cortis

30、ol and urinary 17-OH17-OHLoss of rhythm of plasma cortisol,ACTHLoss of rhythm of plasma cortisol,ACTHLoss of normal suppressibility of cortisol by low-dose Loss of normal suppressibility of cortisol by low-dose dexamethasonedexamethasone 第四十二页，共七十页。实验室检查实验室检查(jinch)(jinch)皮质醇分泌增多，失去昼夜分泌节律，且皮质醇分泌增多，失

31、去昼夜分泌节律，且不能被小剂量地塞米松抑制试验所抑制不能被小剂量地塞米松抑制试验所抑制尿尿1717羟皮质类固醇、游离皮质醇增高羟皮质类固醇、游离皮质醇增高(znggo)(znggo)血浆皮质醇浓度增高血浆皮质醇浓度增高小剂量地塞米松抑制试验小剂量地塞米松抑制试验第四十三页，共七十页。皮质醇分泌增多皮质醇分泌增多(zn du)(zn du)，失去昼夜，失去昼夜节律，不能被小剂量地塞米松抑制节律，不能被小剂量地塞米松抑制第四十四页，共七十页。Diagnosis and Differential Diagnosis and Differential diagnosisdiagnosis诊断诊断(zh

32、ndun)(zhndun)和鉴别诊断和鉴别诊断(zhndun)(zhndun)第四十五页，共七十页。DiagnosisDiagnosis The clinical diagnosis of Cushings The clinical diagnosis of Cushings syndrome is confirmed by clinical syndrome is confirmed by clinical presentation,cortisol presentation,cortisol hypersecretion,loss of normal rhythm hypersecreti

33、on,loss of normal rhythm in cortisol and loss of normal in cortisol and loss of normal suppressibility of cortisol by low-suppressibility of cortisol by low-dose dexamethasonedose dexamethasone第四十六页，共七十页。诊诊 断断临床表现临床表现皮质醇分泌增多，失去昼夜分泌节律皮质醇分泌增多，失去昼夜分泌节律尿尿17-17-羟皮质醇和游离皮质醇增高羟皮质醇和游离皮质醇增高(znggo)(znggo)不能被小剂

34、量地塞米松所抑制不能被小剂量地塞米松所抑制第四十七页，共七十页。病病 因因 诊诊 断断第四十八页，共七十页。CushingCushing s s disease disease adenomaadenocarcinomaEctopic ACTH syndromeUrinary 17-OH,Urinary 17-OH,17-KS,17-KS,cortisol High-dose dex High-dose dex suppression testsuppression testY YNNNNNNACTH ACTH Hypokalemia Hypokalemia alkali poisoninga

35、lkali poisoning Y Y(sometimes)(sometimes)NNY YY YCT of sella turcicaCT of sella turcica Y YNNNNNNCT,MRI of CT,MRI of Adrenal Bilateral Bilateral hyperplasia hyperplasia tumourtumourtumourtumourBilateral Bilateral hyperplasia hyperplasia 第四十九页，共七十页。第五十页，共七十页。Differential diagnosisDifferential diagnos

36、is Cushings syndrome needs to identify with the Cushings syndrome needs to identify with the following diseasesfollowing diseasesSimple obesity Simple obesity Type 2 diabetes Type 2 diabetes AlcoholismAlcoholism and hepatic lesion and hepatic lesion Depressive disorderDepressive disorder第五十一页，共七十页。鉴

37、别鉴别(jinbi)(jinbi)诊断诊断2 2型糖尿病：临床表现、皮质醇节律正常型糖尿病：临床表现、皮质醇节律正常单纯性肥胖：地米抑制单纯性肥胖：地米抑制(yzh)(yzh)试验、皮质醇节律正常试验、皮质醇节律正常酗酒兼有肝损害者，出现假性酗酒兼有肝损害者，出现假性cushingcushing综合症综合症 抑郁症：临床表现抑郁症：临床表现第五十二页，共七十页。TreatmentTreatment Treatment of Cushing syndrome is aimed at Treatment of Cushing syndrome is aimed at following goals

38、:following goals:Cure of the syndrome by reduction of cortisol Cure of the syndrome by reduction of cortisol secretion to normalsecretion to normalEradication of any tumor threatening the Eradication of any tumor threatening the health of patientshealth of patientsPrevention of permanent dependency

39、on Prevention of permanent dependency on medicationsmedicationsAvoidance of permanent hormone deficiencyAvoidance of permanent hormone deficiency 第五十三页，共七十页。Treatment-cushing diseaseTreatment-cushing diseaseTranssphenoidal microadenomectomy is the most Transsphenoidal microadenomectomy is the most r

40、ational current treatment for Cushing diseaserational current treatment for Cushing diseaseIn patients who are not cured by this treatment,three In patients who are not cured by this treatment,three options remainoptions remainReoperate on the pituitary glandReoperate on the pituitary glandRadiate t

41、he pituitary glandRadiate the pituitary glandPerform surgical adrenalectomy and corticoid antagonist Perform surgical adrenalectomy and corticoid antagonist 第五十四页，共七十页。cushingcushing病的治疗病的治疗(zhlio)(zhlio)经蝶窦切除微腺瘤，是本病的首选经蝶窦切除微腺瘤，是本病的首选(shu xun)(shu xun)方法方法一侧肾上腺全切，另一侧肾上腺全部或大部分切除，术后可能并发一侧肾上腺全切，另一侧肾上腺全

42、部或大部分切除，术后可能并发NelsonNelson综合症综合症开颅手术治疗，如不能全部切除，可在术后辅以放疗开颅手术治疗，如不能全部切除，可在术后辅以放疗阻滞肾上腺皮质激素合成的药物阻滞肾上腺皮质激素合成的药物第五十五页，共七十页。Treatment-Adrenocortical adenomaTreatment-Adrenocortical adenomaand adenocarcinomaand adenocarcinomaSmall adenomas can be removed by Small adenomas can be removed by laparascopylapara

43、scopyLarge adenomas and carcinomas require Large adenomas and carcinomas require an open flank or transabdominal an open flank or transabdominal approachapproachThe cure with surgical removal of The cure with surgical removal of adrenal adenoma is virtually 100%adrenal adenoma is virtually 100%第五十六页

44、，共七十页。肾上腺腺瘤、腺癌肾上腺腺瘤、腺癌(xin i)(xin i)的治疗的治疗肾上腺腺瘤手术可获根治肾上腺腺瘤手术可获根治(gnzh)(gnzh)，术后采用氢化可的松替代，术后采用氢化可的松替代腺癌应尽可能早作手术，如不能，采用药物治疗腺癌应尽可能早作手术，如不能，采用药物治疗 第五十七页，共七十页。Treatment-Ectopic ACTH syndromeTreatment-Ectopic ACTH syndromeWhen possible,the tumor should be surgically excised,When possible,the tumor should

45、be surgically excised,removing the source of ectopic ACTH and thereby curing the removing the source of ectopic ACTH and thereby curing the metabolic disordermetabolic disorderIn most patients,however,the tumor is nonresectable at the In most patients,however,the tumor is nonresectable at the time o

46、f diagnosis.time of diagnosis.Chemotherapy or radiation therapy,or both may be Chemotherapy or radiation therapy,or both may be helpfulhelpful第五十八页，共七十页。异位异位(y wi)(y wi)ACTHACTH综合症的治疗综合症的治疗治疗原发性的恶性肿瘤治疗原发性的恶性肿瘤手术手术(shush)(shush)、放疗、化疗放疗、化疗使用肾上腺皮质激素合成阻滞药使用肾上腺皮质激素合成阻滞药第五十九页，共七十页。Adrenal enzyme inhibito

47、rsAdrenal enzyme inhibitorsO,p-DDD O,p-DDD AminoglutethimideAminoglutethimideSU4885SU4885KetoconazoleKetoconazole 第六十页，共七十页。肾上腺皮质激素合成肾上腺皮质激素合成(hchng)(hchng)阻滞药阻滞药米托坦米托坦氨鲁米能氨鲁米能美替拉酮美替拉酮 酮康唑酮康唑第六十一页，共七十页。手术手术(shush)(shush)前后的处理前后的处理患者血浆皮质醇浓度很高，一旦切除相患者血浆皮质醇浓度很高，一旦切除相关肿瘤，皮质醇分泌量锐减，有可能发关肿瘤，皮质醇分泌量锐减，有可能发生急

48、性肾上腺皮质功能不全的危险生急性肾上腺皮质功能不全的危险手术手术(shush)(shush)前后均需补充糖皮质激素前后均需补充糖皮质激素第六十二页，共七十页。PrognosisPrognosisCushing disease will be better after Cushing disease will be better after virtually treatmentvirtually treatmentThe prognosis with adrenal adenoma The prognosis with adrenal adenoma is excellent because

49、surgery is is excellent because surgery is usually curativeusually curativeThe prognosis with adrenal carcinoma The prognosis with adrenal carcinoma is poor because most patients have is poor because most patients have distant metastases at diagnosisdistant metastases at diagnosis第六十三页，共七十页。预预 后后经过有

50、效的治疗经过有效的治疗(zhlio)(zhlio)，病情好转，症状减轻，病情好转，症状减轻癌的预后取决于是否早期发现及能否完全切除癌的预后取决于是否早期发现及能否完全切除肾上腺腺瘤的预后最好肾上腺腺瘤的预后最好CushingCushing病疗效不一，应定期观察病疗效不一，应定期观察第六十四页，共七十页。如需鉴别如需鉴别(jinbi)(jinbi)库欣综合征与单纯性肥胖，下库欣综合征与单纯性肥胖，下列各项中最有意义的检验或试验是：列各项中最有意义的检验或试验是：A A 血皮质醇测定血皮质醇测定B 24B 24小时尿小时尿17-17-羟、羟、17-17-酮酮C 24C 24小时尿游离皮质醇小时尿游