Liu Minghao, Hamele-Bena Diane, Ausiello John, Page-Wilson Gabrielle
Endocrinology Division, Department of Medicine, Columbia University Medical Center, 650 West 168th St., Room 2012, New York, NY 10032, USA.
Department of Pathology and Cell Biology, Columbia University Medical Center, Physicians and Surgeons Building, Room 404, 630 W 168th St., New York, NY 10032, USA.
Case Rep Endocrinol. 2019 May 28;2019:6583467. doi: 10.1155/2019/6583467. eCollection 2019.
Ectopic ACTH syndrome (EAS) arising years after the diagnosis of a neuroendocrine tumor (NET) is exceedingly rare. We describe a case of EAS occurring five years after the diagnosis of a metastatic lung NET in a 61-year-old woman. She presented with severe hypokalemia but was not overtly Cushingoid on exam. Serum cortisol was 61mcg/dL after an overnight 1mg dexamethasone suppression test (<1.8mcg/dL) and urinary free cortisol was 7544 mcg/24h (<45mcg/24h), establishing the diagnosis of Cushing's syndrome. Plasma levels of peptides which have been associated with EAS, Agouti-related peptide (AgRP) and the ACTH precursors POMC (31-kDa) and pro-ACTH (22-kDa), were elevated. Metyrapone was initiated, but hypercortisolism persisted and the patient succumbed to pneumonia shortly after presentation. Retrospective examination of biopsy tissues showed rare ACTH immunoreactivity at the time of initial diagnosis, followed by staining in a greater proportion of cells as the disease progressed, consistent with EAS arising years after the diagnosis of NET. Given the increase in mortality associated with EAS, this unusual case highlights the importance of early detection and raises the possibility that early immunohistochemical stains for ACTH and measurements of ACTH precursors may facilitate the identification of NETs at high risk for EAS.
神经内分泌肿瘤（NET）诊断多年后出现的异位促肾上腺皮质激素（ACTH）综合征（EAS）极为罕见。我们描述了一例61岁女性在转移性肺NET诊断五年后发生EAS的病例。她表现为严重低钾血症，但检查时无明显库欣貌。过夜1mg地塞米松抑制试验后血清皮质醇为61mcg/dL（<1.8mcg/dL），尿游离皮质醇为7544 mcg/24小时（<45mcg/24小时），确诊为库欣综合征。与EAS相关的肽，刺鼠相关肽（AgRP）以及ACTH前体阿黑皮素原（POMC，31-kDa）和促ACTH（22-kDa）的血浆水平升高。开始使用甲吡酮，但高皮质醇血症持续存在，患者在就诊后不久死于肺炎。对活检组织的回顾性检查显示，初始诊断时ACTH免疫反应罕见，随着疾病进展，更多比例的细胞出现染色，这与NET诊断多年后出现的EAS一致。鉴于EAS相关死亡率增加，这一罕见病例突出了早期检测的重要性，并增加了早期ACTH免疫组化染色和ACTH前体测量可能有助于识别有EAS高风险的NETs的可能性。
