胰腺神经内分泌肿瘤肝转移合并异位ACTH综合征1例报道

本文回顾性分析1例胰腺神经内分泌肿瘤(pancreatic neuroendocrine tumor,p NET)患者,因胃泌素瘤行手术治疗,术后出现肿瘤肝转移合并出现异位ACTH分泌症状,经动脉栓塞、生长抑素等治疗后症状控制良好。p NET在生长及转移过程中可能出现去分化改变,临床表现为分泌激素类型的变化。综合运用手术、动脉栓塞、生长抑素等治疗手段有助于改善预后。     

胃肠胰神经内分泌肿瘤的肿瘤微环境

肿瘤微环境为肿瘤提供了特有的营养代谢环境,使得肿瘤细胞生物学行为受到自身遗传学及其周边微环境的双重调控.胃肠胰神经内分泌肿瘤(gastroenteropancreatic neuroendocrine neoplasms,GEP-NENs)是起源于消化系统神经内分泌细胞的异质性肿瘤,它以分泌生物活性物质为特点.GEP-NENs早期症状不典型,确诊时常已发生转移,对其肿瘤微环境的研究有助于我们进一步认识GEP-NENs的发生发展机制,并能为临床诊断、治疗GEP-NENs提供新的依据.本篇文章综述了肿瘤微环境中不同细胞成分、细胞外基质重塑蛋白、可溶性生长因子以及嗜铬粒蛋白在GEP-NENs进展中的作用.     

胃肠胰神经内分泌肿瘤诊治新进展

神经内分泌肿瘤(neuroendocrine neoplasm,NEN)起源于具有胺前体摄取和脱羧能力的神经内分泌细胞,具有显著异质性。根据其胚胎起源,NEN一般被分为前肠、中肠、后肠肿瘤。前肠肿瘤发生于呼吸道、胸腺、胃、十二指肠和胰腺。中肠肿瘤发生于小肠、阑尾和升结肠。后肠肿瘤发生于横结肠、降结肠和直肠。美国国家癌症研究所肿瘤流行病学监测及最终结果数据库、西班牙国家癌症登记中心、挪威和瑞典的国家癌症登记中心最新数据表明,欧美人群NEN发病率约为2.5/10万～5.0/10万[1-4]。过去30年间,NEN 患病率从1.09 /10万上升至5.25/10万。     

胃肠胰神经内分泌肿瘤诊治进展

在机体经典的内分泌腺体之外,肺、胃肠道等还广泛散在地分布着许多具有内分泌作用的细胞,这些细胞不但本身含有胺,具有摄取胺前体并脱羧的能力,而且与神经细胞有许多共同的形态、生物学和功能特性,故称为神经内分泌细胞。起源于胃肠道和胰腺神经内分泌细胞的肿瘤即胃肠胰神经内     

胃肠胰神经内分泌肿瘤诊治进展

在机体经典的内分泌腺体之外，肺、胃肠道等还广泛散在地分布着许多具有内分泌作用的细胞，这些细胞不但本身含有胺，具有摄取胺前体并脱羧的能力，而且与神经细胞有许多共同的形态、生物学和功能特性，故称为神经内分泌细胞。起源于胃肠道和胰腺神经内分泌细胞的肿瘤即胃肠胰神经内分泌细胞肿瘤（GEP-NET）。这是一组罕见的、有着不同临床表现的肿瘤，其发病约占所有消化道肿瘤的2％，在这类肿瘤中最常见的是类癌，其发病率大约为2．5／10万。     

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。     

隐匿性异位ACTH综合征

一例 38岁男性被诊断为Ｃｕｓｈｉｎｇ综合征。生化检查显示低钾血症和高皮质醇血症 ,且不能被大剂量地塞米松抑制 ,提示是一种异位的或肾上腺源性的Ｃｕｓｈｉｎｇ综合征。血促肾上腺皮质激素水平 >1 0 0ＩＵ Ｌ。垂体磁共振成像、胸部放射成像、计算机Ｘ线断层扫描及气管镜检查均正常。肾上腺成像有腺体增生但无腺瘤 ,行 1 1 1Ｉｎ标记奥曲肽扫描 ,左侧胸部近中线位置有一区域示踪物质吸收增加。给患者行甲双吡丙酮治疗并双侧肾上腺切除 ,但术后死亡。尸检发现垂体正常 ,双侧肾上腺增生 ,左侧肺门气管示踪物质吸收增加的区域有一肿瘤样结…     

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     

胃肠胰神经内分泌肿瘤的治疗研究进展

胃肠胰神经内分泌肿瘤（GEP-NETs）起源于胃肠胰腺神经内分泌细胞,是一组罕见的、有着不同临床表现的肿瘤。在过去的30a中,GEP—NETs发病率快速增长。为此,美国国家癌症中心已大幅提高GEP—NETs的研究经费,以促进GEP—NETs的基础和临床诊治的研究。我国GEP—NETs发病率也逐年增加,但其治疗效果一直不甚理想。现将近年来GEP—NETs的治疗研究进展情况综述如下。     

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。     

Ectopic ACTH syndrome associated with ovarian steroid-cell tumor

Several cases of ovarian neoplasms resulting in Cushing's syndrome due to ectopic secretion of ACTH or ectopic secretion of F have been reported. Tumors producing ACTH include adenocarcinoma, androblastoma, Sertoli cell carcinoma, carcinoid tumor and teratoma. Cortisol secretion has been reported in ovarian steroid cell tumor (unclassified steroid cell tumor). We present a case of a 19-year-old woman with Cushing's syndrome in course of an ovarian steroid cell tumor with ectopic ACTH production. To our knowledge, it is the first reported case of ACTH secreting ovarian steroid cell tumor causing Cushing's syndrome.     

Ectopic ACTH syndrome associated with large-cell neuroendocrine carcinoma of the lung

Although ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a well-known paraneoplastic phenomenon, an association with large-cell neuroendocrine carcinoma of the lung (LCNEC) has not been reported. We describe a 63-year-old man with metastatic LCNEC to the left temporomandibular joint (TMJ) who presented with progressive muscle weakness and bilateral lower leg edema for 2 weeks. He did not have a typical Cushingoid appearance nor used diuretics. His newly noted hypertension, hypokalemia (plasma potassium (K) concentration 1.8 mEq/L) with renal K wasting, and metabolic alkalosis suggested a state of mineralocorticoid excess. His plasma renin activity and aldosterone concentrations were low, but cortisol and ACTH levels were extremely elevated, consistent with ACTH-dependent Cushing's syndrome. Nonsuppressible plasma cortisol level and normal sella turcica on magnetic resonance imaging pointed to EAS. A strongly positive stain for ACTH from the metastatic left TMJ mass supported LCNEC-related EAS. His hypokalemia and hypertension were controlled with spironolactone and K supplementation. This is the first reported case of EAS in LCNEC and should be kept in mind as a cause of hypokalemia in lung cancer patients.     

胸腺类癌致异位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 2 5例[1 7] 。现报告一例引起异位ACTH综合征的胸腺类癌。男性患者 ,44岁 ,因“肤色变黑、体重增加两年 ,伴乏力、浮肿 1个月余”于 2 0 0 2年 7月 17日入院。患者于 2 0 0 0年起逐渐出现肤色变黑、体重增加。2 0 0 1年 8月因肤色变黑明显 ,曾至当地医院就诊 ,肝肾功能等常规检查未发现异常。 2 0 0 2年 6月初无明显诱因下出现全身乏力伴双下肢凹陷性水肿 ,并逐渐加重 ,但无纳差…     

Ectopic ACTH syndrome due to salivary gland adenoid cystic carcinoma.

A 68-year-old woman developed Cushing syndrome associated with a submaxillary salivary gland adenoid cystic carcinoma. High levels of immunoreactive adrenocorticotrophic hormone (ACTH) were found in the tumor and peripheral blood. Urinary 17-hydroxycorticosteroid levels decreased following administration of dexamethasone, suggesting possible suppression of ectopic ACTH production. however, there was no specific in vitro binding of dexamethasone by tumor cytosol. A trial of metyrapone therapy resulted in control of hypokalemia and hyperglycemia. Both plasma cortisol and 11-deoxycortisol levels decreased with metyrapone administration, suggesting that this agent may inhibit not only 11-beta-hydroxylation, but also possibly earlier steps in glucocorticoid synthesis.     

Ectopic ACTH syndrome

Ectopic adrenocorticotropic secretion (EAS) is responsible for 12-17% of cases of Cushing's syndrome (CS) and covers a range of tumours, from undetectable benign lesions to widespread metastases. The syndrome is often associated with severe hypercortisolaemia, which aggravates the underlying condition. EAS requires a complete workup that includes the establishment of endogenous CS, diagnosis of adrenocorticotropic hormone (ACTH) dependency, localization of the source of ACTH secretion and rapid biochemical control of hypercortisolaemia. Dynamic endocrine tests should include inferior petrosal sinus sampling with CRH stimulation. Localization studies depend on the availability of reliable high-resolution cross-sectional imaging. This systematic review of the largest published series of patients with EAS (over 380 patients) reveals the common trends in the prevalence and management of this syndrome. The concept of 'occult' EAS has been revisited and the terms 'overt' and 'covert' EAS introduced. In addition to small cell lung carcinoma, the most common causes of ectopic EAS are bronchial carcinoids, thymic tumours, islet cell tumour of the pancreas, medullary thyroid carcinomas, and phaeochromocytomas. Their prevalence and the best localization modalities are presented. Medical and surgical management is discussed on the basis of the extensive experience of major referral centres.     

异位ACTH综合征的研究进展

能引起异位促肾上腺皮质激素(ACTH)综合征的肿瘤种类较多,β连环蛋白相关的Wnt信号通路、Nouch信号通路、P21活化的蛋白激酶3在异位分泌ACTH肿瘤的发生、发展中起重要作用,促阿片黑素细胞皮质素原基凶启动子区去甲基化与肿瘤异位分泌激素密切相关.在诊疗方面,血清嗜铬粒蛋白A的测定大大提高了异位ACTH综合征的阳性预测率.除手术治疗外,联合用药较单独使用生长抑素或选择性多巴胺受体激动剂更为有效.     

Ectopic ACTH syndrome associated with large cell neuroendocrine carcinoma of the thymus

A 38-year-old man was admitted for evaluation of Cushing's syndrome. Physical findings showed swelling of the face, and hypertension, but not Cushingoid stigmata. Laboratory data revealed serum cortisol level of 34.1 μg/dL and plasma ACTH of 140 pg/mL. Overnight administration of 1 and 8 mg dexamethasone did not suppress plasma ACTH or serum cortisol. Chest X-ray showed a mass at the upper-anterior quadrant of the mediastinum, and chest CT scan revealed a heterogenous tumor of approximately 60 mm in diameter, which infiltrated into the superior vena cava and ascending aorta, and caused superior vena cava syndrome. The tumor was resected. Histological examination indicated large cell neuroendocrine carcinoma of the thymus and positive immunoreactivity for ACTH. Ten days after the operation, the plasma ACTH decreased as low as 13.7 pg/mL. The present study indicates that large cell neuroendocrine carcinoma of the thymus can cause superior vena cava syndrome and ectopic ACTH syndrome.