庫欣綜合征曾正陪

1、庫欣綜合征,曾正陪北京協(xié)和醫(yī)院內(nèi)分泌科,,庫欣綜合征的發(fā)現(xiàn),,腎上腺的結(jié)構(gòu),球狀帶,,束狀帶,,網(wǎng)狀帶,,髓質(zhì),,,庫欣綜合征的病因從激素分泌分類,庫欣綜合征的病因從激素分泌分類,庫欣綜合征(Cushing syndrome,皮質(zhì)醇增多癥) Since cortisol production by the adrenal glands is normally under the control of the pituitary

2、 (like the thyroid gland), overproduction can be caused by a tumor in the pituitary or within the adrenal glands themselves. 因垂體或腎上腺腫瘤分泌過多皮質(zhì)醇所致的一組癥候群庫欣病(Cushing disease) When a pituitary tumor secretes too much

3、 ACTH (Adrenal Cortical Tropic Hormone), it simply causes the otherwise normal adrenal glands to produce too much cortisol. This type of Cushings syndrome is termed "Cushings Disease“. In this case, serum cortiso

4、l will be elevated, and, serum ACTH will be elevated at the same time.因垂體瘤分泌過多促腎上腺皮質(zhì)激素(ACTH),刺激腎上腺分泌過多皮質(zhì)醇所致的庫欣綜合征,庫欣綜合征的病因從病變部位分類,垂體瘤（Pituitary Adenomas）Pituitary adenomas cause most cases of Cushing's syndrome. Th

5、ey are benign, or non-cancerous, tumors of the pituitary gland which secrete increased amounts of ACTH. Most patients have a single adenoma. This form of the syndrome, known as "Cushing's disease," affects

6、women five times more frequently than men.異位ACTH綜合征(Ectopic ACTH Syndrome) Some benign or malignant (cancerous) tumors that arise outside the pituitary can produce ACTH. This condition is known as ectopic ACTH syndrome

7、. Lung tumors cause over 50 percent of these cases. Men are affected 3 times more frequently than women. The most common forms of ACTH-producing tumors are oat cell, or small cell lung cancer, which accounts for about 25

8、 percent of all lung cancer cases, and carcinoid tumors. Other less common types of tumors that can produce ACTH are thymomas, pancreatic islet cell tumors, and medullary carcinomas of the thyroid.,庫欣綜合征的病因從病變部位分類,腎上腺腫瘤(

9、Adrenal Tumors) Sometimes, an abnormality of the adrenal glands, most often an adrenal tumor, causes Cushing's syndrome. The average age of onset is about 40 years. Most of these cases involve non-cancerous tumors o

10、f adrenal tissue, called adrenal adenomas, which release excess cortisol into the blood. Adrenocortical carcinomas, or adrenal cancers, are the least common cause of Cushing's syndrome. Cancer cells secrete exce

11、ss levels of several adrenal cortical hormones, including cortisol and adrenal androgens. Adrenocortical carcinomas usually cause very high hormone levels and rapid development of symptoms.,庫欣綜合征的病因,家族性庫欣綜合征(Familial Cus

12、hing's Syndrome)Most cases of Cushing's syndrome are not inherited. Rarely, however, some individuals have special causes of Cushing's syndrome due to an inherited tendency to develop tumors of one or more e

13、ndocrine glands. In Primary Pigmented Micronodular Adrenal Disease, children or young adults develop small cortisol-producing tumors of the adrenal glands. In Multiple Endocrine Neoplasia Type I (MEN I), hormone secretin

14、g tumors of the parathyroid glands, pancreas and pituitary occur. Cushing's syndrome in MEN I may be due to pituitary, ectopic or adrenal tumors.,病 因 比例（%） ACTH依賴性

15、 80 庫欣病 68 異位ACTH綜合癥 12 異位CRH綜合癥 〈1ACTH非依賴性

16、 20 腎上腺腺瘤 10 腎上腺腺癌 8 雙側(cè)腎上腺小結(jié)節(jié)增生 1 大結(jié)節(jié)增生 〈1

17、 引自“Williams Textbook of Endocrinology", 第9版,庫欣綜合癥病因分類和相對比例,Causes of Adrenal Cushing ’s Syndrome,,,庫欣綜合征的發(fā)病率,it is relatively rare and most commonly affects adults aged 20 to 50

18、. An estimated 10 to 15 of every million people are affected each year. 庫欣病發(fā)病率在美國每百萬人口每年發(fā)病約5-25例。我國尚無確切的流行病資料。男女性別之比為1:3-8，男女差別極為顯著，原因尚不明。庫欣病可發(fā)生在任何年齡，以25-45歲為多見。,庫欣綜合征的臨床表現(xiàn),庫欣綜合征的臨床表現(xiàn),癥狀或體征

19、 出現(xiàn)頻率(%) 向心性肥胖 79-97 多血質(zhì) 50-94 糖耐量受損 39-90

20、 無力及近端肌病 29-90 高血壓 74-87 心理改變 31-86 瘀斑

21、 23-84 女子多毛 64-81 月經(jīng)稀發(fā)或閉經(jīng) 55-80,庫欣綜合征的臨床表現(xiàn),癥狀或體征

22、 出現(xiàn)頻率(%) 陽痿 55-80 痤瘡、皮膚多油 26-80 紫紋

23、 51-71 水腫 28-60 背痛、病理性骨折 40-50 多飲、多尿 25-44 腎結(jié)

24、石 15-19 色素沉著 4-16 頭痛 0-47 突眼

25、 0-33,庫欣綜合征的診斷,定性診斷—確定是否為庫欣綜合征？ 臨床表現(xiàn)--癥狀、體征 實(shí)驗(yàn)室檢查 血漿皮質(zhì)醇水平測定 皮質(zhì)醇晝夜節(jié)律消失 單次血皮質(zhì)醇測定診斷價(jià)值不大 24小時(shí)尿游離皮質(zhì)醇(24h

26、UFC)濃度測定 可避免血皮質(zhì)醇的瞬時(shí)變化 避免血中皮質(zhì)醇結(jié)合球蛋白（CBG) 的影響 診斷符合率98%,庫欣綜合征的診斷,定性診斷—確定是否為庫欣綜合征？ 小劑量地塞米松抑制試驗(yàn) 地塞米松0.5mg g6h x 2天 留24小時(shí)尿--對照日及服藥第二天

27、 服藥第二天24hUFC 90% 胰島素低血糖試驗(yàn) 正常人—血ACTH及F增高 庫欣綜合征—低血糖應(yīng)激不能引起血ACTH及F水平顯著上升,庫欣綜合征的診斷,定位診斷—明確庫欣綜合征的病因 大劑量地塞米松抑制試驗(yàn) 地塞米松2mg g6h x 2天 留24小時(shí)尿--對照日及服藥第二天 庫欣病--服藥第二

28、天24hUFC被抑制到對照日50%以下 診斷符合率80% 腎上腺腺瘤或腺癌--不能被抑制到50%以下 異位ACTH綜合征—大多不被抑制,庫欣綜合征的診斷,定位診斷—明確庫欣綜合征的病因 血ACTH水平測定 腎上腺皮質(zhì)腫瘤—血ACTH水平低于正常低限 庫欣病、異位A

29、CTH綜合征—血ACTH水平不同程度升高 異位ACTH綜合征 顯性腫瘤—ACTH明顯高于庫欣病 隱性腫瘤—ACTH與庫欣病重疊 血ACTH測定對鑒別ACTH依賴性和非依賴性有肯定的意義 對鑒別垂體性或異位ACTH分泌僅作參考,庫欣綜合征的診斷,定位診

30、斷—明確庫欣綜合征的病因 甲吡酮試驗(yàn)—鑒別垂體性或腎上腺性 750mg g4h x 1天，24小時(shí)后 庫欣病人—血N-POMC顯著升高 異位ACTH綜合征—變化不明顯 CRH興奮試驗(yàn)—鑒別庫欣病或異位ACTH綜合征 靜注羊CRH 1-41 100µg 或1 µg /kg體重

31、 庫欣病---血ACTH、F水平顯著上升 異位ACTH綜合征—無反應(yīng) 靜脈插管分段取血測定ACTH濃度--鑒別庫欣病或異位ACTH綜合征 對垂體ACTH瘤及異位ACTH綜合征進(jìn)行定位,,,,,,,,,,,,,,CRH,HYPOTHALAMUS,PITUITARYADENOMA,,,,,ADRENAL,GLANDS,CUSHING DISE

32、ASE,,,,ACTH,PLASMA CORTISOL,,,,,,NEGATIVE,FEEDBACK,,William E. Winter, MD,,,,,,,NEGATIVE,FEEDBACK,,,,,,,,,,,,,,CRH: suppressed,HYPOTHALAMUS,PITUITARY,,,,,ADRENAL,GLANDS,Ectopic ACTH,,,,ACTH,PLASMA CORTISOL,,,,,,NEGATIVE,

33、FEEDBACK,,William E. Winter, MD,,,,,,Pit. ACTH: suppressed*,* overall: ACTH is elevated,,,,NEGATIVE,FEEDBACK,,,,,,,,,,,,,,CRH: suppressed,HYPOTHALAMUS,PITUITARY,,,,,ADRENAL,ADENOMA,Adrenal adenoma,,,,PLASMA CORTIS

34、OL,,,,,,NEGATIVE,FEEDBACK,,William E. Winter, MD,,,,ACTH: suppressed,,,,NEGATIVE,FEEDBACK,庫欣綜合征的診斷,定位診斷—明確庫欣綜合征的病因 影象學(xué)檢查 腎上腺—B超、CT、MRI 131I-膽固醇掃描 垂體—80-90%為微腺瘤 C

35、T、MRI（MRI優(yōu)于CT） 胸片 其他部位x線檢查,治療及預(yù)后,庫欣病—經(jīng)鼻經(jīng)蝶竇垂體瘤摘除術(shù) 治愈率>80% 復(fù)發(fā)率10%左右 垂體放療 腎上腺手術(shù)腎上腺瘤-腎上腺瘤手術(shù) 術(shù)后短期補(bǔ)充糖皮質(zhì)激素,治療及預(yù)后,異位ACTH瘤

36、 手術(shù)切除腫瘤 局部放療藥物治療 密妥坦(O,P-DDD)-抑制皮質(zhì)醇合成 氨基導(dǎo)眠能-抑制皮質(zhì)醇合成 甲吡酮-11羥化酶抑制劑,庫欣綜合征的藥物治療,80%近期治愈10-30%復(fù)發(fā),30-50%未治愈,垂體放射治療,40%治愈（其中85%為18歲以下青年人）,60%未治愈（可避免出現(xiàn)Nelson綜合癥,密妥坦,20%未治愈,80%治愈,腎上腺酶抑制劑,雙側(cè)腎上腺全切術(shù),治愈,,,,,,,,,,