1、Site of secretionFemaleMaleBronchial carcinoid tumor112Small cell lung carcinoma15Medullary thyroid carcinoma3Pancreatic carcinoid tumor12Thymic carcinoid tumor1Disseminated carcinoid tumor1Mesothelioma1Pancreatic carcinoma1Colonic carcinoma1Phaechromocytoma1Gall bladder carcinoma1Total1616Etiology
2、of the ectopic ACTH syndrome in patients seen at St.Bartholomews Hospital 1969-2001一、皮质醇过多引起的表现一、皮质醇过多引起的表现1、脂肪代谢紊乱和脂肪重新分布、脂肪代谢紊乱和脂肪重新分布2、蛋白分解加速，、蛋白分解加速，合成减少合成减少3、葡萄糖利用减少，糖原异生作用增加、葡萄糖利用减少，糖原异生作用增加4、电解质紊乱、电解质紊乱5、GH分泌减少，作用受抑制分泌减少，作用受抑制6、性腺功能受抑制、性腺功能受抑制7、精神异常、精神异常8、抵抗力下降、抵抗力下降二、二、其他激素分泌过多的临床表现其他激素分泌过多的
3、临床表现1、雄激素过多、雄激素过多2、盐皮质激素过多、盐皮质激素过多3、ACTH过多过多三、三、肿瘤本身引起的临床表现肿瘤本身引起的临床表现1、腹块、腹块2、蝶鞍扩大、蝶鞍扩大3、异源性、异源性ACTH综合症引起的局部症状综合症引起的局部症状(肺癌、支气管类癌、胸腺癌等肺癌、支气管类癌、胸腺癌等)SymptomsSignsWeight gain Truncal obesityMenstrual irregularity PlethoraHirsuitism in women Moon faceHeadache HypertensionThirst BruisingBack pain Stria
4、eMuscle weakness Buffalo humpAbdominal pain AcneLethargy/depression Osteoporosis皮质醇增多的临床表现皮质醇增多的临床表现满月脸（满月脸（90%90%）向心性肥胖（向心性肥胖（85%85%）糖耐量异常（糖耐量异常（85%85%）高血压高血压(80%)(80%)性功能紊乱性功能紊乱(75%)(75%)骨质疏松骨质疏松(65%)(65%)紫纹紫纹(60%)(60%)四肢无力四肢无力(65%)(65%)多毛多毛(70%)(70%)水肿水肿(55%)(55%)水牛背水牛背(55%)(55%)痤疮痤疮(55%)(55%)精神异
5、常精神异常(45%)(45%)ShorthistoryWeightlossSeveremyopathyPigmentationHypokalemicalkalosisVeryhighplasmaACTHOvertneoplasm,usuallysmallcelllungcarcinoma一、激素测定一、激素测定皮质醇及其周期皮质醇及其周期ACTH及其周期及其周期尿尿/唾液游离皮质醇测定唾液游离皮质醇测定二、动态试验二、动态试验1、抑制试验、抑制试验a.午夜地塞米松抑制试验午夜地塞米松抑制试验b.小剂量地塞米松抑制试验小剂量地塞米松抑制试验c.大剂量地塞米松抑制试验大剂量地塞米松抑制试验d.me
6、tyraponetest查查17-OH和和plasmadeoxycortisol2、兴奋试验、兴奋试验a.CRHtestb.ACTHtestc.hypoglycemiatest三、影像学检查三、影像学检查1、pituitaryimaging2、meta-iodobenylquanidinescanning3、simultaneousbilateralinferiorpetrosalsinussampling明确高皮质醇血症明确高皮质醇血症血皮质醇；血皮质醇；24h尿游离皮质醇；尿游离皮质醇；小剂量地塞米松抑制试验；小剂量地塞米松抑制试验；胰岛素低血糖试验；胰岛素低血糖试验；明确病因分类明确病因
7、分类大剂量地塞米松抑制试验；大剂量地塞米松抑制试验；血血ACTH；甲吡酮试验；甲吡酮试验；CRH兴奋试验；兴奋试验；静脉导管分段取血测静脉导管分段取血测ACTH；影像学检查；影像学检查；o疑有疑有CushingsCushingsa.典型临床表现典型临床表现b.24小时小时UFC或或17-OH升高升高c.血浆皮质醇分泌失去正常节律血浆皮质醇分泌失去正常节律d.午夜地塞米松抑制试验阳性午夜地塞米松抑制试验阳性o确诊确诊CushingsCushingsa.小剂量地塞米松抑制试验阳性小剂量地塞米松抑制试验阳性b.血浆皮质醇对胰岛素诱发的低血糖无反应血浆皮质醇对胰岛素诱发的低血糖无反应Serum ACT
8、H Low in adrenal disease,high in pituitary and ectopic production CRH test Increased ACTH following CRH in pituitary disease No increase in ACTH following CRH in ectopic production High-dose dexamethasone suppression test(2 mg qds for 2 days)Serum cortisol reduced by high-dose in pituitary disease S
9、uppression of urinary free cortisol to less than 10%of baseline Pituitary CT has a sensitivity of about 50%for identifying microadenomas MRI has increased sensitivity but is not 100%predictive If diagnostic doubt need bilateral inferior petrosal sinus sampling for ACTH Abdominal CT will allow identi
10、fication of adrenal pathology Somatostatin scintigraphy to identify sites of ectopic hormone production Physiological statesPregnancy Stress Chronic excessive exercise Malnutrition Pathological states Cushings syndrome Diabetes mellitus Hyperthyroidism Severe chronic disease Glucocorticoid resistanc
11、e Psychological states Anorexia nervosa Panic disorder Melancholic depression Obsessive-compulsive disorder 库欣病库欣病肾上腺皮质瘤肾上腺皮质瘤肾上腺皮质癌肾上腺皮质癌异位异位ACTH综合征综合征尿 尿-17羟 羟中度增多中度增多中度增多中度增多明显增高明显增高较肾上腺皮质癌更高较肾上腺皮质癌更高尿 尿-17酮 酮中度增多中度增多正常或增高正常或增高明显增高明显增高明显增高明显增高血、尿皮质醇血、尿皮质醇轻中度增多轻中度增多轻中度增多轻中度增多重度升高重度升高较肾上腺皮质癌更高较肾上腺皮
12、质癌更高大剂量地塞米松抑制试验大剂量地塞米松抑制试验 能被抑制能被抑制不能抑制不能抑制不能抑制不能抑制不能抑制不能抑制血 血ACTH清晨高于正常，晚上不下降清晨高于正常，晚上不下降 下降下降下降下降明显增高明显增高CRH兴奋试验兴奋试验正常反应或过度反应正常反应或过度反应无反应无反应无反应无反应无反应无反应ACTH兴奋试验兴奋试验有反应，高于正常有反应，高于正常约半数无反应，半数有反应约半数无反应，半数有反应 无反应无反应有反应有反应美替拉酮试验美替拉酮试验有反应，高于正常有反应，高于正常无反应无反应无反应无反应部分有反应，部分无反应部分有反应，部分无反应低血钾性碱中毒低血钾性碱中毒严重者可有
13、严重者可有无 无常有常有常有常有蝶鞍区蝶鞍区CT及 及MRI蝶鞍扩大蝶鞍扩大不扩大不扩大不扩大不扩大不扩大不扩大放射性碘化胆固放射性碘化胆固双肾上腺显影、增大双肾上腺显影、增大瘤侧显影、增大瘤侧显影、增大癌侧显影或不显影癌侧显影或不显影两侧显影、增大两侧显影、增大醇肾上腺扫描醇肾上腺扫描肾上腺超声、肾上腺超声、CT及 及MRI 双侧肾上腺增大双侧肾上腺增大显示肿瘤显示肿瘤显示肿瘤显示肿瘤两侧肾上腺增大两侧肾上腺增大Transphenoidalsurgery:success rate：approximately 90%Large tumours occasional require open s
14、urgery via the anterior fossa Post-operative radiotherapy occasionally required If pituitary surgery fails need to consider bilateral adrenalectomy 25%patients develop Nelsons syndrome after bilateral adrenalectomy Adrenal adenomas require adrenalectomy Performed either laparoscopically or via open
15、surgery Open surgery can be performed via a transabdominal or retroperitoneal approachGeneralconsiderationslAdrenolyticTherapyMetyrapone、Ketoconazole、Aminoglutethimide、Mitotane(o.pDDD)、Etomidate.lNeuromodulatoryagents5-HTAntagonists：Cyproheptadine、Ritanserin；DopamineAgonists：Bromocriptine；Somatostat
16、inAnalogues：Octreotide；GABAAgonists：SodiumValproate.lReceptorblockadeGlucocorticoidAntagonists：Mifepristone(RU486).o Specific receptor antagonistso Cholinergic pathwayo Anti-muscarinic agents o Retinoic acidTransphenoidalAdrenalectomySurgeryforectopicACTHsyndrome术前12小时及2小时各肌注醋酸可的松50mg,术后肌注50mg q6h,术后第三日起减量至q8h，第五日减量为q12h术中静滴氢可200mg,术后再滴注100mgo氢化可的松氢化可的松2030mg或可的松或可的松2537.5mgo根据肾上腺皮质功能调整替代治疗剂量根据肾上腺皮质功能调整替代治疗剂量o一般一般612个月内停止替代治疗个月内停止替代治疗 自愈率低 未经治疗死亡率为50%伴动脉硬化或骨质疏松者致残率高预预后后28 结束语结束语
