Carey R M, Varma S K, Drake C R, Thorner M O, Kovacs K, Rivier J, Vale W
N Engl J Med. 1984 Jul 5;311(1):13-20. doi: 10.1056/NEJM198407053110103.
Corticotropin-releasing factor, a hypophyseo-tropic hormone that stimulates adrenocorticotropic hormone (ACTH) secretion, has recently been isolated, characterized, and synthesized in the sheep and rat. We report on a patient with metastatic carcinoma of the prostate presenting with anterior and posterior pituitary hormone deficiency together with ACTH-dependent Cushing's syndrome. At postmortem examination, large areas of the median eminence and pituitary stalk were replaced by tumor, but the corticotrophs were markedly hyperplastic. Immunostaining of tumor cells was positive for corticotropin-releasing factor and was negative for ACTH and a wide range of other hormones. Radioimmunoassay and bioassays showed that tumor extracts and further purified fractions were active in corticotropin-releasing factor, and the tumor material coeluted with corticotropin-releasing factor on high-pressure liquid chromatography. These studies demonstrate that ectopic secretion of corticotropin-releasing factor is a cause of Cushing's syndrome in human beings. The features of this syndrome include hypercortisolism, pituitary corticotroph hyperplasia, elevation of circulating ACTH levels, and failure to suppress the pituitary-adrenal axis with exogenous glucocorticoids.
促肾上腺皮质激素释放因子是一种刺激促肾上腺皮质激素（ACTH）分泌的促垂体激素，最近已在绵羊和大鼠中被分离、鉴定并合成。我们报告了一例前列腺癌转移患者，该患者同时出现垂体前叶和后叶激素缺乏以及ACTH依赖性库欣综合征。尸检时，下丘脑正中隆起和垂体柄的大片区域被肿瘤取代，但促肾上腺皮质激素细胞明显增生。肿瘤细胞免疫染色促肾上腺皮质激素释放因子呈阳性，ACTH及多种其他激素呈阴性。放射免疫分析和生物分析表明，肿瘤提取物和进一步纯化的组分具有促肾上腺皮质激素释放因子活性，且肿瘤物质在高压液相色谱上与促肾上腺皮质激素释放因子共洗脱。这些研究表明，促肾上腺皮质激素释放因子的异位分泌是人类库欣综合征的一个病因。该综合征的特征包括皮质醇增多症、垂体促肾上腺皮质激素细胞增生、循环ACTH水平升高以及外源性糖皮质激素不能抑制垂体-肾上腺轴。
