庫(kù)欣綜合征-曾正陪.ppt

1、庫(kù)欣綜合征,曾正陪 北京協(xié)和醫(yī)院內(nèi)分泌科,庫(kù)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(kù)欣綜合征的病因從激素分泌分類,庫(kù)欣綜合征的病因從激素分泌分類,庫(kù)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 (like the thyroid gland), overproduction can be caused by a tumor in the pituitary or with

2、in the adrenal glands themselves. 因垂體或腎上腺腫瘤分泌過(guò)多皮質(zhì)醇所致的一組癥候群 庫(kù)欣病(Cushing disease) When a pituitary tumor secretes too much 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 Diseas

3、e“. In this case, serum cortisol will be elevated, and, serum ACTH will be elevated at the same time.因垂體瘤分泌過(guò)多促腎上腺皮質(zhì)激素(ACTH),刺激腎上腺分泌過(guò)多皮質(zhì)醇所致的庫(kù)欣綜合征,庫(kù)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 Cushings syndrome. They are benign, or non-cancerous, tumors of the pituitary

4、 gland which secrete increased amounts of ACTH. Most patients have a single adenoma. This form of the syndrome, known as Cushings disease, affects 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

5、can produce ACTH. This condition is known as ectopic ACTH syndrome. 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 percent of al

6、l 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(kù)欣綜合征的病因從病變部位分類,腎上腺腫瘤(Adrenal Tumors) Sometimes, an abnormality of the adrenal glands, most often an adrenal tumor,

7、causes Cushings syndrome. The average age of onset is about 40 years. Most of these cases involve non-cancerous tumors of adrenal tissue, called adrenal adenomas, which release excess cortisol into the blood. Adrenocortical carcinomas, or adrenal cancers, are the least common cause of Cushings syndr

8、ome. Cancer cells secrete excess 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(kù)欣綜合征的病因,家族性庫(kù)欣綜合征(Familial Cushings Syndrome)Most cases of Cushings syndrome are

9、 not inherited. Rarely, however, some individuals have special causes of Cushings syndrome due to an inherited tendency to develop tumors of one or more endocrine glands. In Primary Pigmented Micronodular Adrenal Disease, children or young adults develop small cortisol-producing tumors of the adrena

10、l glands. In Multiple Endocrine Neoplasia Type I (MEN I), hormone secreting tumors of the parathyroid glands, pancreas and pituitary occur. Cushings syndrome in MEN I may be due to pituitary, ectopic or adrenal tumors.,病 因 比例（%） ACTH依賴性 80 庫(kù)欣病 68 異位ACTH綜合癥 12 異位CRH綜合癥 1 ACTH非依賴性 20 腎上腺腺瘤 10 腎上腺腺癌 8

11、雙側(cè)腎上腺小結(jié)節(jié)增生 1 大結(jié)節(jié)增生 1 引自“Williams Textbook of Endocrinology, 第9版,庫(kù)欣綜合癥病因分類和相對(duì)比例,Causes of Adrenal Cushings Syndrome,庫(kù)欣綜合征的發(fā)病率,it is relatively rare and most commonly affects adults aged 20 to 50. An estimated 10 to 15 of every million people are affected each year. 庫(kù)欣病發(fā)病率在美國(guó)每百萬(wàn)人口每年發(fā)病約5-25例。我國(guó)尚無(wú)確切的流行病

12、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(kù)欣病可發(fā)生在任何年齡，以25-45歲為多見(jiàn)。,庫(kù)欣綜合征的臨床表現(xiàn),庫(kù)欣綜合征的臨床表現(xiàn),癥狀或體征 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 無(wú)力及近端肌病 29-90 高血壓 74-87 心理改變 31-86 瘀斑 23-84 女子多毛 64-81 月經(jīng)稀發(fā)或閉經(jīng) 55-80,庫(kù)欣綜合征的臨床表現(xiàn),癥狀或體征 出現(xiàn)頻率(%) 陽(yáng)痿 55-80 痤瘡、皮膚多油 26-80 紫紋 51-71 水腫 28-60 背痛、病理性骨折 40-50 多飲、多尿 25-44 腎結(jié)石 15-19 色

13、素沉著 4-16 頭痛 0-47 突眼 0-33,庫(kù)欣綜合征的診斷,定性診斷確定是否為庫(kù)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(cè)定 皮質(zhì)醇晝夜節(jié)律消失 單次血皮質(zhì)醇測(cè)定診斷價(jià)值不大 24小時(shí)尿游離皮質(zhì)醇(24hUFC)濃度測(cè)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(kù)欣綜合征的診斷,定性診斷確定是否為庫(kù)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(duì)照日及服藥第二天 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(kù)欣綜合征低血糖應(yīng)激不能引起血ACTH及

14、F水平顯著上升,庫(kù)欣綜合征的診斷,定位診斷明確庫(kù)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(duì)照日及服藥第二天 庫(kù)欣病-服藥第二天24hUFC被抑制到對(duì)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(kù)欣綜合征的診斷,定位診斷明確庫(kù)欣綜合征的病因 血ACTH水平測(cè)定 腎上腺皮質(zhì)腫瘤血ACTH水平低于正常低限 庫(kù)欣病、異位ACTH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(kù)欣病 隱性腫瘤ACTH與庫(kù)欣病重疊 血ACTH測(cè)定對(duì)鑒別ACTH依賴性和非依賴性有肯定

15、的意義 對(duì)鑒別垂體性或異位ACTH分泌僅作參考,庫(kù)欣綜合征的診斷,定位診斷明確庫(kù)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(kù)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(kù)欣病或異位ACTH綜合征 靜注羊CRH 1-41 100g 或1 g /kg體重 庫(kù)欣病-血ACTH、F水平顯著上升 異位ACTH綜合征無(wú)反應(yīng) 靜脈插管分段取血測(cè)定ACTH濃度-鑒別庫(kù)欣病或異位ACTH綜合征 對(duì)垂體ACTH瘤及異位ACTH綜合征進(jìn)行定位,CRH,HYPOTHALAMUS,PITUITARY ADENOMA,ADRENAL,GLA

16、NDS,CUSHING DISEASE,ACTH,PLASMA CORTISOL,NEGATIVE,FEEDBACK,William E. Winter, MD,NEGATIVE,FEEDBACK,CRH: suppressed,HYPOTHALAMUS,PITUITARY,ADRENAL,GLANDS,Ectopic ACTH,ACTH,PLASMA CORTISOL,NEGATIVE,FEEDBACK,William E. Winter, MD,Pit. ACTH: suppressed*,* overall: ACTH is elevated,NEGATIVE,FEEDBACK,CRH:

17、 suppressed,HYPOTHALAMUS,PITUITARY,ADRENAL,ADENOMA,Adrenal adenoma,PLASMA CORTISOL,NEGATIVE,FEEDBACK,William E. Winter, MD,ACTH: suppressed,NEGATIVE,FEEDBACK,庫(kù)欣綜合征的診斷,定位診斷明確庫(kù)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 CT、MRI（MRI優(yōu)于CT） 胸片 其他部位x線檢查,治療及預(yù)后,庫(kù)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 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(kù)欣綜合征的藥物治療,80%近期治愈 10-30%復(fù)發(fā),30-50%未