胸腺类癌致异位促肾上腺皮质激素综合征手术复发后经米非司酮治疗缓解一例

<正>患者,女,55岁,工人,因“乏力2个月,加重1天”于2016年3月13日就诊于我科。患者2个月前出现乏力,无头晕、胸闷、多尿、口干、多饮,外院查血钾<2.00 mmol/L(3.50～5.30 mmol/L,括号内为正常参考值范围,以下相同),诊断为“低钾血症”,经补钾对症处理后乏力减轻。1天前,患者再次出现四肢乏力,于我院查血钾2.09 mmol/L(3.50～5.50 mmol/L),以“低钾血症原因待查”收住院。自发病以来,患者饮食、睡眠可,大小便无明显异常,近2个月体重较前增加5 kg。既往史：高血压病2年,     

支气管类癌致异位ACTH综合征

我们报告1例支气管炎上起的异位ACTH综合征，进行了较为深入的临床研究。该例有典型的柯兴氏综合征的临床表现，生化和内分泌检查结果和柯兴氏病吻合，曾误为垂体ACTH瘤而作了经蝶窦垂体探查术，术后无改善而作进一步检查，胸部CT发现右上肺有一哑铃状阴影，静脉插管分段取务测N－POMC示失去正常梯度，动脉血N－POMC水平高于静脉务.砌除右上肺肿瘤（1．8×1×1cm^3)加肺门放疗后临床表现得到缓解，血N－POMC和皮质醇明显下降，病理实为支气管类癌，有肺门淋巴结转移。免疫组化及放免疫测定证明肿瘤细胞内含有大量ACTH及其相关肽，凝胶过滤示大分子免疫活性物质（ACTH前体分子POMC）占很大比例。     

胸腺类癌致异位ACTH综合征

目的 总结胸腺类癌引起的异位ACTH综合征临床表现，提高对此综合征的诊断率。方法 分析6例患者的临床表现，尤其是非典型胸腺类癌所致异位ACTH综合征的症状和体征、实验室相关测定值以及影像学表现。结果 6例患者均行胸腺肿瘤切除术并经病理证实为胸腺类癌导致异位ACTH综合征。结论 有明确库欣综合征临床表现，且伴有低血钾，浮肿，蛋白尿且出现不能解释的8mg地塞米松抑制试验不被抑制，均应考虑异位ACTH综合征，胸腺类癌是异位ACTH综合征的可能病因。     

老年肺癌合并异位促肾上腺皮质激素综合征2例

异位促肾上腺皮质激素综合征(ectopic adrenocorticotropic hormone syndrome,EAS)是库欣综合征的一种特殊类型,是由于垂体以外的肿瘤组织分泌过量的有生物活性的促肾上腺皮质激素(Adrenocorticotropic hormone,ACTH)刺激肾上腺皮质增生,从而产生过量皮质类固醇而引起的临床综合征。老年肺癌     

异位ACTH综合征研究进展

异位ACTH综合征（EAS）是Cushing综合征的一种特殊类型，是由于垂体以外的肿瘤组织分泌过量有生物活性的促肾上腺皮质激素（ACTH），刺激肾上腺皮质增生，产生过量皮质类固醇引起的临床综合征，占Cushing综合征患者总数的5％～10％。文献报道，最多见的病因为肺部或支气管肿瘤，约占50％，其次为胸腺及胰腺肿瘤，各约占10％，还可有甲状腺髓样癌、嗜铬细胞瘤及胃肠道、生殖系统、前列腺等部位的肿瘤。目前大部分异位ACTH综合征的肿瘤定位不能明确，给临床诊断和治疗带来很大困难。近年来，异位ACTH综合征课题组在异位ACTH的临床和基础研究中做了一定的工作，现整理如下。     

异位促肾上腺皮质激素综合征

<正>概述异位促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)综合征(ectopic ACTH syndrome,EAS)作为库欣综合征的一种特殊类型,是因垂体以外ACTH的肿瘤组织分泌过量具有生物活性的ACTH,刺激肾上腺皮质增生并产生过量皮质类固醇引起的临床综合征,占库欣综合征患者总数的5%～10%^[1]。国外文献报道最多见病因为肺部或支气管肿瘤,约占50%,其次分别为胸腺及胰腺肿瘤,各约占10%,还可有甲状腺髓样癌(medullary thyroid carcinoma,MTC),嗜铬细胞瘤,胃肠道及生殖系统、前列腺等部位的肿瘤^[2]。     

胸碌类癌致异位ACTH综合征一例报告

异位ACTH综合征约占库欣综合征病因的10%左右，其中胸腺类癌所致者约占异源病因的2%-4%。1972年由Rosai和Higa首次报告以来，在英文文献中报告的共约有25例。现报告一例引起异位ACTH综合征的胸腺类癌。     

继发于脑膜瘤的异位促肾上腺皮质激素综合征一例

患者男，61岁。5个月前出现颜面及双下肢水肿，夜尿增多．5～6次／晚，食欲增加，但体重无明显增加，乏力渐明显，生活不能自理，近1个月血压160／100mmHg（1mmHg=0．133kPa)，右跟视力下降，降压利尿浩疗，疗效不佳。无头痛、恶心、呕吐，无毛发增多，无畏寒、发热，无咳嗽、咳痰、腹痛、腹泻。体检：BP150／90mmHg，体重指数21．9kg/m^2，神清，无满月脸、水牛背及向心性肥胖,无皮肤紫纹、痤疮，面部及胸部皮肤发红、全身浅表淋巴结不大，眼睑水肿，眼球活动自如，瞳孔对光反射正常，颈软，甲状腺不大，心肺正常，腹部未扪及包头，肝脾未及，双下肢轻度水肿，四肢肌力、肌张力正常。膝反射减弱，病理征阴性。     

三例甲状腺髓样癌导致的异位CRH综合征病例总结及文献复习

目的:探究甲状腺髓样癌导致库欣综合征的病因。方法:收集自2011年4月至今在本院住院的3例甲状腺髓样癌合并库欣综合征患者。所有患者年龄在40至50岁之间,包括1例女性和2例男性。检测患者的血压、血糖、甲状腺功能及抗体、降钙素、癌胚抗原,完善库欣综合征相关定性定位检查,包括大、小剂量地塞米松抑制试验及影像学,并取活检标本...     

肾上腺嗜铬细胞瘤致异位ACTH综合征的临诊应对

肾上腺嗜铬细胞瘤引起的异位ACTH综合征非常罕见.本文详细介绍1例肾上腺嗜铬细胞瘤引起异位ACTH综合征临床特点并结合国内外研究进展,讨论其诊治.提出正确的诊断应结合临床、生化、激素分泌、影像学、病理学、肿瘤免疫组化染色进行最终的综合判断.     

"类癌致异位促肾上腺皮质激素综合征病例报道"专家点评

异位促肾上腺皮质激素(ACTH)综合征属库欣综合征的一种特殊类型,其发病机制是非垂体的肿瘤组织分泌过量的具有生物活性的ACTH或ACTH类似物,刺激肾上腺皮质增生并分泌过量的皮质醇引起的临床综合征.引起异位ACTH综合征的最常见病因为肺癌,尤其是小细胞肺癌,约占50%.但"类癌与异位ACTH综合征"一文的特点是总结了临床较为少见的类癌引起异位ACTH综合征的病例,主要因为:(1)类癌引起异位ACTH综合征发病率有增加的趋势,如以往有关类癌致异位ACTH综合征的报道仅占异位ACTH综合征的10%,但在20世纪80年代以后的病例报道中,类癌的比例增大,约占36%～46%.     

异位ACTH综合征6例临床分析

目的 提高临床医生对异位ACTH综合征的认识。方法 对四川大学华西医院1996-2005年确诊的6例异位ACTH综合征患者的临床资料及诊治过程进行回顾性分析。结果 副节瘤1例，神经内分泌癌1例，肺癌4例。临床特征：病程15d至2个月，6例患者均有严重低血钾伴碱中毒，5例患者有高血压和双下肢水肿。Cushing综合征表现：满月脸4例，淤斑和长胡须2例，多血质、痤疮、色素沉着各1例，血皮质醇（晨起8时）〉1173nmol／L，大剂量地塞米松（8mg）抑制试验均不能抑制。结论 对病程短，严重低血钾碱中毒，水肿明显而Cushing临床表现不明显者，血皮质醇〉1000nmol／L应高度怀疑异位ACTH综合征。寻找病因，尽快手术切除肿瘤，近期预后较好。     

异位ACTH综合征6例临床分析

目的提高临床医生对异位ACTH综合征的认识。方法对四川大学华西医院1996—2005年确诊的6例异位ACTH综合征患者的临床资料及诊治过程进行回顾性分析。结果副节瘤1例,神经内分泌癌1例,肺癌4例。临床特征病程15d至2个月,6例患者均有严重低血钾伴碱中毒,5例患者有高血压和双下肢水肿。Cushing综合征表现满月脸4例,淤斑和长胡须2例,多血质、痤疮、色素沉着各1例,血皮质醇(晨起8时)>1173nmol/L,大剂量地塞米松(8mg)抑制试验均不能抑制。结论对病程短,严重低血钾碱中毒,水肿明显而Cushing临床表现不明显者,血皮质醇>1000nmol/L应高度怀疑异位ACTH综合征。寻找病因,尽快手术切除肿瘤,近期预后较好。     

探讨促肾上腺皮质激素兴奋在肾上腺静脉取血中的应用价值

目的:探讨促肾上腺皮质激素(ACTH)兴奋在肾上腺静脉取血(AVS)中的应用价值。方法:纳入完成常规AVS和ACTH兴奋的AVS,且至少有一种AVS双侧肾上腺静脉插管成功的原发性醛固酮增多症(原醛症)患者。计算选择指数(SI)、优势侧指数(LI),比较ACTH兴奋与否对插管成功率及优势侧判断的影响。结果:共纳入73名原...     

Clinically silent congenital adrenal hyperplasia masquerading as ectopic adrenocorticotropic hormone syndrome

A 64-year-old man with an asymptomatic pulmonary mass discovered on routine chest roentgenography was found to have substantial bilateral adrenal enlargement by abdominal computed tomography. Percutaneous adrenal aspiration biopsy showed cytologically normal adrenal glands. A diagnosis of subclinical 21-hydroxylase deficiency was established by stimulation testing with adrenocorticotropic hormone. The adrenal size and appearance by computed tomographic scanning in congenital adrenal hyperplasia and particularly in its subclinical form have not been well defined. This case demonstrates that marked adrenal enlargement can occur and may provide the only clue to the diagnosis in an asymptomatic patient without other clinical stigmata of adrenal hyperplasia.     

Two cases of ectopic adrenocorticotropic hormone syndrome with olfactory neuroblastoma and literature review

Olfactory neuroblastomas are rare, slow-growing malignant tumors, usually diagnosed at advanced stages. Ectopic adrenocorticotropic hormone (ACTH) syndrome caused by an olfactory neuroblastoma is extremely rare. We reported two Korean women who suffered from ectopic ACTH syndrome (EAS) caused by olfactory neuroblastomas. The first patient was a 66-year-old woman who had been diagnosed as olfactory neuroblastoma and refused the management two years before and the second patient was a 37-year-old woman on chemotherapy for olfactory neuroblastoma. In the first case, she presented the Cushingoid appearance with systemic edema and her tumor was removed surgically. ACTH secretion by the tissue was confirmed by immunohistochemistry. By contrast, the second patient presented as severe pneumonia caused by cytomegalovirus and was treated with anti-viral agent followed by chemotherapy and radiotherapy, and her residual mass remained. However, after treatment, both patients' plasma ACTH and cortisol levels returned to normal without any adrenolytic therapy. Considering the causative tumors of EAS can be rarely cured and EAS increases the susceptibility to infections, it is prudent to suppress any hypercortisolemia initially, apart from treating the causal malignancy.     

Neuroendocrine tumors secreting growth hormone-releasing hormone: Pathophysiological and clinical aspects

Hypothalamic GHRH is secreted into the portal system, binds to specific surface receptors of the somatotroph cell and elicits intracellular signals that modulate pituitary GH synthesis and/or secretion. Moreover, GHRH is synthesized and expressed in multiple extrapituitary tissues. Excessive peripheral production of GHRH by a tumor source would therefore be expected to cause somatotroph cell hyperstimulation, increased GH secretion and eventually pituitary acromegaly. Immunoreactive GHRH is present in several tumors, including carcinoid tumors, pancreatic cell tumors, small cell lung cancers, endometrial tumors, adrenal adenomas, and pheochromocytomas which have been reported to secrete GHRH. Acromegaly in these patients, however, is uncommon. The distinction of pituitary vs. extrapituitary acromegaly is extremely important in planning effective management. Regardless of the cause, GH and IGF-1 are invariably elevated and GH levels fail to suppress (<1 μg/l) after an oral glucose load in all forms of acromegaly. Dynamic pituitary tests are not helpful in distinguishing acromegalic patients with pituitary tumors from those harbouring extrapituitary tumors. Plasma GHRH levels are usually elevated in patients with peripheral GHRH-secreting tumors, and are normal or low in patients with pituitary acromegaly. Unique and unexpected clinical features in an acromegalic patient, including respiratory wheezing or dyspnea, facial flushing, peptic ulcers, or renal stones sometimes are helpful in alerting the physician to diagnosing non pituitary endocrine tumors. If no facility to measure plasma GHRH is available, and in the absence of MRI evidence of pituitary adenoma, a CT scan of the thorax and abdominal ultrasound could be performed to exclude with good approximation the possibility of an ectopic GHRH syndrome. Surgical resection of the tumor secreting ectopic GHRH should be the logical approach to a patient with ectopic GHRH syndrome. Standard chemotherapy directed at GHRH-producing carcinoid tumors is generally unsuccessful in controlling the activated GH axis. Somatostatin analogs provide an effective option for medical management of carcinoid patients, especially those with recurrent disease. In fact, long-acting somatostatin analogs may be able to control not only the ectopic hormonal secretion syndrome, but also, in some instances, tumor growth. Therefore, although cytotoxic chemotherapy, pituitary surgery, or irradiation still remain available therapeutic options, long-acting somatostatin analogs are now preferred as a second-line therapy in patients with carcinoid tumors and ectopic GHRH-syndrome.     

以基因芯片技术研究胸腺类癌引起异位ACTH综合征的基因表达

目的　研究引起异位ACTH综合征的胸腺类癌组织与正常胸腺组织的基因表达差异,探讨胸腺类癌引起异位ACTH综合征的发病机制。方法　利用基因芯片技术,通过不同荧光(Cy3和Cy5)标记的对照和胸腺类癌组织RNA样本与芯片杂交,观察两种组织间的基因差异表达。结果　研究发现,基因芯片的4 224个基因中403个基因在胸腺类癌组织中表达下调, 394个基因表达上调2倍以上(其中23个与细胞分裂有关), 51个基因上调5倍以上(其中与细胞分裂有关的基因1个,即PAK3)。结论　引起异位ACTH综合征的胸腺类癌组织与正常胸腺组织存在多个差异表达的基因,PAK3可能参与了该肿瘤的发生。