Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo, Japan.
Department of Pathology, The University of Tokyo, Tokyo, Japan.
Endocr J. 2019 Jun 28;66(6):547-554. doi: 10.1507/endocrj.EJ18-0563. Epub 2019 Mar 28.
Ectopic ACTH syndrome (EAS) due to a prostate small cell carcinoma (SCC) is very rare with only 26 cases reported to date and has a poor prognosis. We here describe another case of this disorder that was clinically typical based on prior reports as it showed hypercortisolemia and severe hypokalemia with multiple metastasis. However, our current case of prostate SCC causing EAS is the first to display negative immunostaining for ACTH despite detectable POMC mRNA expression in the primary lesion. ACTH immunonegativity is thought to be associated with a more aggressive disease course and a poorer prognosis although there are few studies of the underlying mechanisms. We explored two possibilities for this finding in our current patient: aberrant POMC processing prevented immunodetection with an anti-ACTH antibody; and the ACTH content per cell was below the threshold for immunodetection due to its rapid secretion or low synthesis. The aberrant processing theory was thought to be less likely because of immunonegative findings even using anti-POMC/ACTH antibodies. As the plasma ACTH levels in our patient were comparable with those reported for previous immunopositive prostate EAS cases, we speculated that the depletion of ACTH may be caused not only by rapid secretion but also by low production levels as a sign of de-differentiation. De-differentiation may therefore explain the mechanism underlying the negative correlation between immunoreactivity for ACTH in EAS and disease aggressiveness. We believe that our present findings will be of use in future prospective studies aimed at confirming the mechanism of immunonegativity.
异位促肾上腺皮质激素综合征（EAS）由前列腺小细胞癌（SCC）引起非常罕见，迄今为止仅报告了 26 例，预后较差。我们在此描述了另一种这种疾病的病例，根据先前的报告，该病例临床表现典型，表现为皮质醇增多症和严重低钾血症，且有多处转移。然而，我们当前的前列腺 SCC 导致 EAS 的病例是首例尽管在原发性病变中检测到 POMC mRNA 表达，但 ACTH 免疫染色阴性的病例。尽管对潜在机制的研究较少，但人们认为 ACTH 免疫阴性与更具侵袭性的疾病过程和更差的预后相关。我们在当前患者中探讨了这种发现的两种可能性：异常的 POMC 处理阻止了抗 ACTH 抗体的免疫检测；由于其快速分泌或低合成，每个细胞的 ACTH 含量低于免疫检测的阈值。由于甚至使用抗 POMC/ACTH 抗体也存在免疫阴性结果，因此异常处理理论被认为不太可能。由于我们患者的血浆 ACTH 水平与先前报道的免疫阳性前列腺 EAS 病例相似，我们推测 ACTH 的耗竭不仅可能是由于快速分泌，还可能是由于低合成水平作为去分化的标志。因此，去分化可能解释了 EAS 中 ACTH 免疫反应性与疾病侵袭性之间的负相关的机制。我们相信，我们目前的发现将有助于未来旨在确认免疫阴性机制的前瞻性研究。
