Isolated adrenocorticotropic hormone deficiency as a form of paraneoplastic syndrome
Isolated adrenocorticotropic hormone deficiency as a form of paraneoplastic syndrome
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DOI：
10.1007/s11102-018-0901-7
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发表时间：
2018-10-01
期刊：
影响因子：
3.8
通讯作者：
Takahashi, Yutaka
中科院分区：
文献类型：
--
作者：
Bando, Hironori;Iguchi, Genzo;Takahashi, Yutaka
目的对于孤立性促肾上腺皮质激素（ACTH）缺乏症（IAD），已提出针对促肾上腺皮质激素的自身免疫；然而，发病机制仍然很大程度上未知。肺大细胞神经内分泌癌（LCNEC）是一种高度恶性神经内分泌肿瘤的肺部肿瘤，据报道在数例病例中通过自身免疫引起副肿瘤综合征。 方法 一名患有孤立性促肾上腺皮质激素（ACTH）激素缺乏症（IAD）的 42 岁女性，在诊断为 IAD 3年后被诊断为大细胞神经内分泌癌（LCNEC）。我们假设 LCNEC 在 IAD 作为副肿瘤综合征的发展中发挥了因果作用，并分析了自身免疫。我们还分析了另一例异位ACTH综合征来证明这一假设。结果LCNEC组织显示异位ACTH表达和淋巴细胞浸润。有趣的是，在外周血中检测到了针对阿片黑皮质素原（POMC）蛋白的自身抗体。尽管患者的血清对促肾上腺皮质激素细胞系 AtT20 细胞中的细胞活力、增殖或 pomc 表达没有表现出任何影响，但患者外周血中的淋巴细胞对 POMC 蛋白发生特异性反应，表明存在细胞毒性 T 淋巴细胞 (CTL)。此外，对另一例异位ACTH综合征的分析显示，淋巴细胞浸润不仅存在于转移性肝脏肿瘤中，而且存在于垂体中。此外，大多数CD8阳性细胞位于促肾上腺皮质激素附近。结论这些数据表明肿瘤中异位ACTH表达引起了促肾上腺皮质激素的自身免疫，并导致IAD作为一种副肿瘤综合征的形式。
PurposeIn isolated adrenocorticoropic hormone (ACTH) deficiency (IAD), autoimmunity against corticotrophs has been suggested; however, the pathogenesis remains largely unknown. Large cell neuroendocrine carcinoma (LCNEC) of the lung is a pulmonary tumor of high-grade malignant neuroendocrine tumor and it reportedly caused paraneoplastic syndrome by autoimmunity in several cases.MethodsA 42-year-old woman with isolated adrenocorticotropic (ACTH) hormone deficiency (IAD) was diagnosed with large cell neuroendocrine carcinoma (LCNEC) 3years after being diagnosed with IAD. We hypothesized that the LCNEC played a causal role in the development of IAD as a paraneoplastic syndrome and analyzed the autoimmunity. We also analyzed another case of ectopic ACTH syndrome to prove this hypothesis.ResultsThe LCNEC tissue revealed an ectopic ACTH expression and lymphocyte infiltration. Interestingly, autoantibody against the proopiomelanocortin (POMC) protein was detected in the peripheral blood. Although, patient's serum did not show any effects on cell viability, proliferation, nor pomc expression in a corticotroph cell line, AtT20 cells, patient's lymphocytes in the peripheral blood specifically reacted toward POMC protein, indicating a presence of cytotoxic T lymphocytes (CTLs). In addition, the analysis of another case of ectopic ACTH syndrome showed lymphocyte infiltration not only in the metastatic liver tumors but also in the pituitary. Moreover, most CD8-positive cells resided adjacent to corticotrophs.ConclusionsThese data indicate that the ectopic ACTH expression in the tumor evoked the autoimmunity to corticotrophs and caused IAD as a form of paraneoplastic syndrome.