Wajchenberg B L, Mendonça B, Liberman B, Adelaide M, Pereira A, Kirschner M A
Endocrine Service, Hospital das Clínicas, University of São Paulo School of Medicine, Brazil.
J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):139-51. doi: 10.1016/0960-0760(95)00044-z.
Ectopic ACTH syndrome represents a cancer-induced amplification of a property [proopiomelanocortin (POMC) peptides production] normally present in the cells from which the cancer originated but with aberrant posttranslational processing of POMC resulting in a greatly elevated secretion of ACTH precursors. The classic ectopic ACTH-producing tumors described in the 1960s were highly malignant but more recently slowly growing tumors such as carcinoids are reported with increasing frequency. Clinical features of patients with ectopic ACTH were analyzed, including biochemical abnormalities, plasma ACTH, cortisol and urinary steroids. Dynamic tests such as high-dose dexamethasone suppression, metyrapone and ovine-CRH (oCRH) stimulation were explored, as well as inferior petrosal sinus ACTH sampling before and after oCRH. Among the tumor markers examined, elevation of ACTH precursors was uniformly present followed by increased output of calcitonin, gut hormones, oncofetal and placental hormones in decreasing order. Since more than 90% of ectopic ACTH tumors are neuroendocrine in nature exhibiting APUD characteristics, their 2 markers, neuron-specific enolase and chromogranins are very useful. The imaging procedures for localization of the tumor ranged from chest X-rays to computed tomography and magnetic resonance of the chest and abdomen. Abdominal ultrasonography was also useful. Finally somatostatin receptor scintigraphy permitted demonstration of unrecognized tumors and/or metastases, even when the tumors were occult. The ACTH content, immunostaining for APUD markers and altered POMC processing were evaluated in ectopic tumors and/or metastases. Occult ectopic ACTH syndrome of more than 4-6 months of symptoms without the emergence of an obvious source was reviewed. Since the tumors are often clinically and biochemically undistinguishable from pituitary-dependent Cushing's disease, inferior petrosal sinus sampling for ACTH after oCRH stimulation established the diagnosis in over 90% of the cases. 60% of the occult tumors were thoracic carcinoids (3/4 bronchial carcinoids), followed by small cell lung cancer and pancreatic neuroendocrine tumors. In 12% the primary etiology was not detected. The rare syndrome of ectopic CRH syndrome (6 published cases) leading to excessive stimulation of the pituitary which became hyperplastic and secreted excessive amounts of ACTH is discussed. Finally, the 12 published cases and 1 unreported patient with ectopic CRH-ACTH tumors were reviewed, the majority being metastatic small cell lung carcinomas, bronchial and thymic carcinoids.
异位促肾上腺皮质激素（ACTH）综合征表现为癌症诱导的一种特性[阿黑皮素原（POMC）肽生成]的放大，这种特性通常存在于癌症起源的细胞中，但POMC的翻译后加工异常，导致ACTH前体的分泌大幅增加。20世纪60年代描述的经典异位产生ACTH的肿瘤具有高度恶性，但最近报道生长缓慢的肿瘤如类癌的频率在增加。分析了异位ACTH患者的临床特征，包括生化异常、血浆ACTH、皮质醇和尿类固醇。探索了动态试验，如高剂量地塞米松抑制试验、甲吡酮试验和羊促肾上腺皮质激素释放激素（oCRH）刺激试验，以及oCRH前后的岩下窦ACTH采样。在所检测的肿瘤标志物中，ACTH前体升高普遍存在，其次是降钙素、胃肠激素、癌胚和胎盘激素的分泌量依次增加。由于超过90%的异位ACTH肿瘤本质上是神经内分泌性的，具有APUD特征，它们的两个标志物，神经元特异性烯醇化酶和嗜铬粒蛋白非常有用。肿瘤定位的影像学检查范围从胸部X线到胸部和腹部的计算机断层扫描和磁共振成像。腹部超声检查也很有用。最后，生长抑素受体闪烁显像能够显示未被识别的肿瘤和/或转移灶，即使肿瘤隐匿。对异位肿瘤和/或转移灶中的ACTH含量、APUD标志物的免疫染色以及POMC加工改变进行了评估。回顾了症状持续超过4至6个月且未出现明显病因的隐匿性异位ACTH综合征。由于这些肿瘤在临床和生化方面通常与垂体依赖性库欣病难以区分，oCRH刺激后岩下窦ACTH采样在超过90%的病例中确立了诊断。60%的隐匿性肿瘤为胸类癌（3/4为支气管类癌），其次是小细胞肺癌和胰腺神经内分泌肿瘤。12%的病例未检测到原发性病因。讨论了罕见的异位促肾上腺皮质激素释放激素（CRH）综合征（6例已发表病例），该综合征导致垂体过度刺激，垂体增生并分泌过量的ACTH。最后，回顾了12例已发表病例和1例未报告的异位CRH - ACTH肿瘤患者，大多数为转移性小细胞肺癌、支气管和胸腺类癌。
