Müller O A, von Werder K
Krankenanstalt Rotes Kreuz, München, Germany.
J Steroid Biochem Mol Biol. 1992 Oct;43(5):403-8. doi: 10.1016/0960-0760(92)90076-u.
The most common ectopic production of a pituitary hormone is the one of ACTH leading to Cushing's syndrome. Ectopic ACTH-hypersecretion is the cause of Cushing's syndrome in 10-15% of all cases. The ACTH-secreting tumours are often oat-cell carcinomas of the lung, less frequently pancreatic cancers, hypernephromas, or C-cell carcinomas of the thyroid. Some of these tumours may be benign or semi-benign as the rare carcinoid tumours and cause great problems in the differential diagnosis of ACTH-dependent hypercortisolism. Out of 173 of our patients with Cushing's syndrome observed in the last 12 years 21 were caused by ectopic ACTH-production. Of these 21 patients 13 have a small cell carcinoma of the lung. The ectopic ACTH-syndrome often has typical clinical features caused by the levels of ACTH and cortisol leading to hypocalcemic alkalosis with muscle weakness and wasting, carbohydrate intolerance, and hypertension with oedema. The survival time in many of these patients is not long enough to allow them to develop typical signs of Cushing's syndrome though they are often highly pigmented. These patients are easily diagnosed. However, patients with small tumours which do not cause very elevated ACTH-levels and who have the more typical clinical signs of full-blown Cushing's syndrome are difficult to recognize. For the differential diagnosis of ACTH-dependent Cushing's syndrome the corticotropin-releasing hormone (CRH) stimulation test and dexamethasone suppression test with high doses are helpful. In special cases the venous sampling procedure for ACTH-measurements is necessary, also CT or NMR is helpful. Ectopic CRH-production is a rare cause of ACTH-dependent Cushing's syndrome. Patients with ectopic CRH-production and consecutive ACTH-hypersecretion from the pituitary have not been studied extensively. There are especially no well documented results of the use of the CRH-stimulation test in vivo in this group of patients with Cushing's syndrome. On the other hand, in the documented cases, not only CRH-, but also ACTH-production was found in the tumours. So far, this rare cause of ACTH-dependent Cushing's syndrome has to be excluded or confirmed by the measurement of endogenous CRH-levels. But until now we have not been able to detect one single case of ectopic CRH-production using a sensitive homologous CRH-radioimmunoassay over a period of more than 8 years in which we have seen nearly 120 newly diagnosed patients with ACTH-dependent Cushing's syndrome. Only in the plasma and tumour tissue of two patients of other groups have we found high CRH-levels.
垂体激素最常见的异位分泌是促肾上腺皮质激素（ACTH）的异位分泌，可导致库欣综合征。在所有库欣综合征病例中，异位ACTH分泌过多是10% - 15%病例的病因。分泌ACTH的肿瘤通常是肺燕麦细胞癌，较少见的是胰腺癌、肾细胞癌或甲状腺C细胞癌。其中一些肿瘤可能是良性或半良性的，如罕见的类癌肿瘤，这给ACTH依赖性皮质醇增多症的鉴别诊断带来很大问题。在过去12年中我们观察的173例库欣综合征患者中，21例是由异位ACTH分泌引起的。在这21例患者中，13例患有肺小细胞癌。异位ACTH综合征通常具有由ACTH和皮质醇水平引起的典型临床特征，导致低钙性碱中毒伴肌肉无力和消瘦、糖耐量异常以及高血压伴水肿。这些患者中的许多人存活时间不够长，以至于无法出现典型的库欣综合征体征，尽管他们通常色素沉着明显。这些患者很容易诊断。然而，肿瘤较小且不会导致ACTH水平大幅升高、具有典型的库欣综合征全面发作临床体征的患者则难以识别。对于ACTH依赖性库欣综合征的鉴别诊断，促肾上腺皮质激素释放激素（CRH）刺激试验和高剂量地塞米松抑制试验很有帮助。在特殊情况下，进行ACTH测量的静脉采血程序是必要的，CT或核磁共振成像（NMR）也有帮助。异位CRH分泌是ACTH依赖性库欣综合征的罕见病因。对异位分泌CRH并导致垂体ACTH分泌过多的患者尚未进行广泛研究。在这组库欣综合征患者中，尤其没有关于体内使用CRH刺激试验的充分记录结果。另一方面，在已记录的病例中，肿瘤中不仅发现了CRH分泌，还发现了ACTH分泌。到目前为止，这种ACTH依赖性库欣综合征的罕见病因必须通过测量内源性CRH水平来排除或确认。但在超过8年的时间里，我们使用灵敏的同源CRH放射免疫测定法，在近120例新诊断的ACTH依赖性库欣综合征患者中，尚未检测到一例异位CRH分泌病例。仅在其他组的两名患者的血浆和肿瘤组织中，我们发现了高CRH水平。
