Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Chiba, 260-8670, Japan.
Department of Diabetes, Endocrinology and Metabolism, Chiba University Hospital, Chiba, 260-8670, Japan.
BMC Endocr Disord. 2017 Sep 2;17(1):54. doi: 10.1186/s12902-017-0203-5.
A functional pituitary adenoma can produce multiple anterior-pituitary hormones, such as growth hormone (GH) -producing adenomas (GHoma) with prolactin or thyrotropin stimulating hormone production in the same lineage. However, it is very rare that acromegaly shows subclinical Cushing's disease (SCD) beyond the lineage. Here we describe the involvement of intratumoral coexistence with 2 types of hormone-producing cells associated with different lineage in acromegaly concomitant with SCD.
In our study, we performed clinical evaluation of the patient showing acromegaly with SCD. To elucidate the mechanisms of this pathology, we analyzed immunohistochemistry and gene expression of anterior-pituitary hormones and transcriptional factors in the resected pituitary tumor. On immunohistochemical staining, most of the tumor cells were strongly stained for GH antibody, while some cells were strongly positive for adrenocorticotropic hormone (ACTH). Gene expression analysis of a transsphenoidal surgery sample of the pituitary gland revealed that ACTH-related genes, such as POMC, Tpit, and NeuroD1 mRNA, had higher expression in the tumor tissue than the nonfunctional adenoma but lower expression compared to an adenoma of typical Cushing's disease. Further, double-labeling detection methods with a fluorescent stain for ACTH and GH demonstrated the coexistence of ACTH-positive cells (GH-negative) among the GH-positive cells in the tumor. Additionally, Pit-1 expression was reduced in the ACTH-positive cells from tumor tissue primary culture.
Here we described a case of a pituitary tumor diagnosed with acromegaly associated with SCD. We performed quantitative-expression analyses of transcriptional factors of the tumor tissue and immunohistochemistry analysis of tumor-derived primary culture cells, which suggested that the multihormonal pituitary adenoma concomitant with Pit-1 and Tpit lineage cells caused acromegaly associated with SCD.
功能性垂体腺瘤可产生多种垂体前叶激素，如生长激素（GH）-产生腺瘤（GH 瘤），在同一谱系中产生催乳素或促甲状腺激素刺激激素。然而，在谱系之外，肢端肥大症表现出亚临床库欣病（SCD）非常罕见。在这里，我们描述了在伴有 SCD 的肢端肥大症中，肿瘤内共存 2 种与不同谱系相关的激素产生细胞的情况。
在我们的研究中，我们对表现为伴有 SCD 的肢端肥大症患者进行了临床评估。为了阐明这种病理的机制，我们分析了切除的垂体肿瘤中垂体前叶激素和转录因子的免疫组织化学和基因表达。在免疫组织化学染色中，大多数肿瘤细胞对 GH 抗体强烈染色，而一些细胞对促肾上腺皮质激素（ACTH）强烈阳性。垂体经蝶窦手术样本的基因表达分析显示，ACTH 相关基因，如 POMC、Tpit 和 NeuroD1 mRNA，在肿瘤组织中的表达高于无功能腺瘤，但低于典型库欣病腺瘤。此外，用 ACTH 和 GH 的荧光染色进行的双标记检测方法表明，在肿瘤细胞中存在 ACTH 阳性细胞（GH 阴性）与 GH 阳性细胞共存。此外，肿瘤组织原代培养中 ACTH 阳性细胞的 Pit-1 表达减少。
在这里，我们描述了一例诊断为伴有 SCD 的肢端肥大症垂体瘤的病例。我们对肿瘤组织的转录因子进行了定量表达分析，并对肿瘤衍生的原代培养细胞进行了免疫组织化学分析，这表明多激素垂体腺瘤伴有 Pit-1 和 Tpit 谱系细胞导致了伴有 SCD 的肢端肥大症。
