库欣综合征-曾正陪.ppt

1、库欣综合征,曾正陪 北京协和医院内分泌科,库欣综合征的发现,肾上腺的结构,球状带,束状带,网状带,髓质,库欣综合征的病因从激素分泌分类,库欣综合征的病因从激素分泌分类,库欣综合征(Cushing syndrome,皮质醇增多症) 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. 因垂体或肾上腺肿瘤分泌过多皮质醇所致的一组症候群 库欣病(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.因垂体瘤分泌过多促肾上腺皮质激素(ACTH),刺激肾上腺分泌过多皮质醇所致的库欣综合征,库欣综合征的病因从病变部位分类,垂体瘤（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. 异位ACTH综合征(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.,库欣综合征的病因从病变部位分类,肾上腺肿瘤(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.,库欣综合征的病因,家族性库欣综合征(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依赖性 80 库欣病 68 异位ACTH综合症 12 异位CRH综合症 1 ACTH非依赖性 20 肾上腺腺瘤 10 肾上腺腺癌 8

11、双侧肾上腺小结节增生 1 大结节增生 1 引自“Williams Textbook of Endocrinology, 第9版,库欣综合症病因分类和相对比例,Causes of Adrenal Cushings Syndrome,库欣综合征的发病率,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. 库欣病发病率在美国每百万人口每年发病约5-25例。我国尚无确切的流行病

12、资料。 男女性别之比为1:3-8，男女差别极为显著，原因尚不明。 库欣病可发生在任何年龄，以25-45岁为多见。,库欣综合征的临床表现,库欣综合征的临床表现,症状或体征 出现频率(%) 向心性肥胖 79-97 多血质 50-94 糖耐量受损 39-90 无力及近端肌病 29-90 高血压 74-87 心理改变 31-86 瘀斑 23-84 女子多毛 64-81 月经稀发或闭经 55-80,库欣综合征的临床表现,症状或体征 出现频率(%) 阳痿 55-80 痤疮、皮肤多油 26-80 紫纹 51-71 水肿 28-60 背痛、病理性骨折 40-50 多饮、多尿 25-44 肾结石 15-19 色

13、素沉着 4-16 头痛 0-47 突眼 0-33,库欣综合征的诊断,定性诊断确定是否为库欣综合征？ 临床表现-症状、体征 实验室检查 血浆皮质醇水平测定 皮质醇昼夜节律消失 单次血皮质醇测定诊断价值不大 24小时尿游离皮质醇(24hUFC)浓度测定 可避免血皮质醇的瞬时变化 避免血中皮质醇结合球蛋白（CBG) 的影响 诊断符合率98%,库欣综合征的诊断,定性诊断确定是否为库欣综合征？ 小剂量地塞米松抑制试验 地塞米松0.5mg g6h x 2天 留24小时尿-对照日及服药第二天 服药第二天24hUFC 90% 胰岛素低血糖试验 正常人血ACTH及F增高 库欣综合征低血糖应激不能引起血ACTH及

14、F水平显著上升,库欣综合征的诊断,定位诊断明确库欣综合征的病因 大剂量地塞米松抑制试验 地塞米松2mg g6h x 2天 留24小时尿-对照日及服药第二天 库欣病-服药第二天24hUFC被抑制到对照日50%以下 诊断符合率80% 肾上腺腺瘤或腺癌-不能被抑制到50%以下 异位ACTH综合征大多不被抑制,库欣综合征的诊断,定位诊断明确库欣综合征的病因 血ACTH水平测定 肾上腺皮质肿瘤血ACTH水平低于正常低限 库欣病、异位ACTH综合征血ACTH水平不同程度升高 异位ACTH综合征 显性肿瘤ACTH明显高于库欣病 隐性肿瘤ACTH与库欣病重叠 血ACTH测定对鉴别ACTH依赖性和非依赖性有肯定

15、的意义 对鉴别垂体性或异位ACTH分泌仅作参考,库欣综合征的诊断,定位诊断明确库欣综合征的病因 甲吡酮试验鉴别垂体性或肾上腺性 750mg g4h x 1天，24小时后 库欣病人血N-POMC显著升高 异位ACTH综合征变化不明显 CRH兴奋试验鉴别库欣病或异位ACTH综合征 静注羊CRH 1-41 100g 或1 g /kg体重 库欣病-血ACTH、F水平显著上升 异位ACTH综合征无反应 静脉插管分段取血测定ACTH浓度-鉴别库欣病或异位ACTH综合征 对垂体ACTH瘤及异位ACTH综合征进行定位,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,库欣综合征的诊断,定位诊断明确库欣综合征的病因 影象学检查 肾上腺B超、CT、MRI 131I-胆固醇扫描 垂体80-90%为微腺瘤 CT、MRI（MRI优于CT） 胸片 其他部位x线检查,治疗及预后,库欣病经鼻经蝶窦垂体瘤摘除术 治愈率80% 复发率10%左右 垂体放疗 肾上腺手术 肾上腺瘤-肾上腺瘤手术 术后短期补充糖皮质激素,治疗及预后,异位ACTH瘤 手术切除肿瘤 局部放疗 药物治疗 密妥坦(O,P-DDD)-抑制皮质醇合成 氨基导眠能-抑制皮质醇合成 甲吡酮-11羟化酶抑制剂,库欣综合征的药物治疗,80%近期治愈 10-30%复发,30-50%未