课件：Cushing综合症.ppt

Cushing syndrome Cushing 综合症,Definition,Cushing syndrome, the constellation of clinical signs and symptoms resulting form chronic glucocorticoid excess, was probably first described in 1899,定 义,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）所致病症的总称 主要临床表现为满月脸，多血质外貌，向心性肥胖、痤疮、皮肤紫纹高血压和骨质疏松等,Aetiology Clinical presentation laboratory examination Diagnosis and differential diagnosis Treatment ( principle) Prognosis,病因分类 临床表现 实验室检查 诊断及鉴别诊断 治疗(原则) 预后,Aetiology 病因分类,Hypothalamus 下丘脑 （CRH） pituitary gland 垂体 （ACTH） adrenal cortex肾上腺皮质 zona glomerulosa zona fasciculata zona reticularis （Aldosterone）（cortisol）（gonadal hormone）,+,+,-,-,Aetiology,ACTH-dependent Cushing syndrome Cushing disease Ectopic ACTH syndrome ACTH- independent Cushing syndrome Adrenocortical adenoma Adrenocortical adenocarcinoma Micronodular adrenal disease Massive macronodular adrenal disease,病因分类,依赖ACTH 的cushing综合症 cushing 病 异位ACTH综合症 非依赖ACTH 的cushing综合症 肾上腺皮质腺瘤 肾上腺皮质癌 原发性色素结节性肾上腺病 大结节性巨大肾上腺病,Clinical feature 各型临床特征,Cushing Disease,It is the most common type of Cushing syndrome, and accounts for about 70% of the syndrome Pathogenesis Most patients have ACTH-secreting anterior pituitary corticortrope microadenomas(10mm in diameter), but a small number have diffuse corticotrope hyperplasia and pituitary macroadenoma,Cushing病,最常见，约占cushing综合症的70%,多见于成人，女性多于男性，是由于垂体分泌过多的ACTH所致 病因 垂体微腺瘤80% 垂体大腺瘤10：压迫、侵袭等症状 下丘脑功能紊乱,Ectopic ACTH syndrome,The majority of patients with ectopic ACTH syndrome have outside pituitary tumor Other sites are pulmonary carcinosis, carcinoid of bronchus, thymic carcinoma pancreatic cancer, chromaffin tumor, medullary carcinoma of thyroid and so on,异位ACTH综合症,继发于垂体以外的恶性肿瘤 小细胞肺癌、支气管类癌、胸腺癌、胰腺癌、嗜铬细胞瘤、神经母细胞瘤 等等 临床上分两型 缓慢进展型 迅速进展型,Adrenocortical adenoma,Patients with adrenal adenoma usually have gradual onset of sign of hypercortisolism, accounts for about 15-20% of the syndrome Adenoma is round or ellipse, diameter is 3-4cm, weight is about 40g,肾上腺皮质腺瘤,多见于成人，男性多于女性 15%-20% 腺瘤呈圆形或椭圆形，直径约3-4cm，重40g左右，包膜完整 其病缓慢，病情中等，多毛及雄激素增多少见,Adrenocortical adenocarcinoma,It occurs in lower than 5% patients of cushing syndrome Patients with adenocarcinoma tend to have a more acute and progressive course and virilizing effects may predominate The bulk of tumor is larger,肾上腺皮质腺癌,占cushing综合症的5以下 瘤体积大（直径5-6cm)，肿瘤可浸润包膜 病情重，进展快，重度cushing综合症的表现(低钾性碱中毒、女性男性化）,Micronodular adrenal disease,The disease is also known as Meadors syndrome About half of patients with this disorder have no distinctive clinical presentation other than being young-always younger than 30 years of age, half younger than 15 years and some infants,原发性色素结节性肾上腺病,此病又称这为Meador综合症或原发性色素 性结节性肾上腺疾病 患者多为儿童和青少年 临床表现：一部分同一般的临床表现 一部分为家族性，呈显性遗传 (Carney综合症）,Massive macronodular adrenal disease 大结节性巨大肾上腺病,Clinical presentation 临床表现,典型病例 重型cushing综合症 早期病例 以并发症为主者 周期性或间歇性,Typical cases典 型 病 例,Clinical presentation1,Progressive obesity is the most common sign. It is usually central, involving the face, neck trunk and abdomen All over the body and nervous system: weakness, change of emotion and so on The skin is atrophic, the stratum corneum is thinned, and there is loss of subcutaneous fat allowing subcutaneous blood vessels to been seen,Clinical presentation2,Cardiovascular complication is a major cause of morbidity and death in untreated Cushing syndrome Moderate hypertension is common Glucocorticoid suppress immune function Inflammatory and febrile responses to bacterial infection are suppressed Dysbolism and sexual disturbance sometimes occur,临床表现1,满月脸、多血质外貌、向心性肥胖,临床表现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 皮肤表现：皮肤薄，微血管脆性增加，易出现淤斑、紫纹, 易合并真菌感染,有时可出现皮肤色素沉着,临床表现2,心血管表现： 高血压心衰、脑血管意外 凝血功能异常(血小板，纤维蛋白原 ），脂代谢紊乱，动静脉血栓 对感染的抵抗力减弱 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 中性粒细胞运动能力，吞噬作用减弱 抗体的形成受到阻抑,2019/8/22,36,可编辑,临床表现3,性功能障碍： 月经减少、不规则、停经、痤疮等 明显男性化（警惕肾上腺癌） 代谢障碍： 脂、蛋白、糖代谢 低钾性碱中毒 ，低钙 骨质疏松，伤口愈合不良，生长发育延迟,重型cushing综合症,多由癌肿所致，病情严重，进展迅速 体重减轻 高血压、浮肿、低钾性碱中毒,早期病例,全身情况较好 以高血压为主 肥胖、向心性的特点不够显著,以并发症为主者,Cushing综合症本身不明显 多以并发症就诊：心衰、脑卒中病理性骨折、精神症状、肺部感染等等,周期性或间歇性,Laboratory examination 实验室检查,Laboratory examination,The laboratory examination of Cushing syndrome is cortisol hypersecretion. Increased urinary excretion of cortisol and urinary 17-OH Loss of rhythm of plasma cortisol, ACTH Loss of normal suppressibility of cortisol by low-dose dexamethasone,实验室检查,皮质醇分泌增多，失去昼夜分泌节律，且不能被小剂量地塞米松抑制试验所抑制 尿17羟皮质类固醇、游离皮质醇增高 血浆皮质醇浓度增高 小剂量地塞米松抑制试验,皮质醇分泌增多，失去昼夜节律，不能被小剂量地塞米松抑制,Diagnosis and Differential diagnosis 诊断和鉴别诊断,Diagnosis,The clinical diagnosis of Cushings syndrome is confirmed by clinical presentation , cortisol hypersecretion, loss of normal rhythm in cortisol and loss of normal suppressibility of cortisol by low-dose dexamethasone,诊 断,临床表现 皮质醇分泌增多，失去昼夜分泌节律 尿17-羟皮质醇和游离皮质醇增高 不能被小剂量地塞米松所抑制,病 因 诊 断,Differential diagnosis,Cushings syndrome needs to identify with the following diseases Simple obesity Type 2 diabetes Alcoholism and hepatic lesion Depressive disorder,鉴别诊断,2型糖尿病：临床表现、皮质醇节律正常 单纯性肥胖：地米抑制试验、皮质醇节律正常 酗酒兼有肝损害者，出现假性cushing综合症 抑郁症：临床表现,Treatment,Treatment of Cushing syndrome is aimed at following goals: Cure of the syndrome by reduction of cortisol secretion to normal Eradication of any tumor threatening the health of patients Prevention of permanent dependency on medications Avoidance of permanent hormone deficiency,Treatment-cushing disease,Transsphenoidal microadenomectomy is the most rational current treatment for Cushing disease In patients who are not cured by this treatment, three options remain Reoperate on the pituitary gland Radiate the pituitary gland Perform surgical adrenalectomy and corticoid antagonist,cushing病的治疗,经蝶窦切除微腺瘤，是本病的首选方法 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Nelson综合症 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,Treatment-Adrenocortical adenoma and adenocarcinoma,Small adenomas can be removed by laparascopy Large adenomas and carcinomas require an open flank or transabdominal approach The cure with surgical removal of adrenal adenoma is virtually 100%,肾上腺腺瘤、腺癌的治疗,肾上腺腺瘤手术可获根治，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,Treatment- Ectopic ACTH syndrome,When possible , the tumor should be surgically excised, removing the source of ectopic ACTH and thereby curing the metabolic disorder In most patients, however , the tumor is nonresectable at the time of diagnosis. Chemotherapy or radiation therapy, or both may be helpful,异位ACTH综合症的治疗,治疗原发性的恶性肿瘤 手术、 放疗、化疗 使用肾上腺皮质激素合成阻滞药,Adrenal enzyme inhibitors,O, p-DDD Aminoglutethimide SU4885 Ketoconazole,肾上腺皮质激素合成阻滞药,米托坦 氨鲁米能 美替拉酮 酮康唑,手术前后的处理,患者血浆皮质醇浓度很高，一旦切除相关