Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar S. João, Porto, Portugal.
Faculty of Medicine, University of Porto, Porto, Portugal.
Endocrine. 2019 Jan;63(1):182-187. doi: 10.1007/s12020-018-1726-x. Epub 2018 Aug 28.
Pituitary adenomas and paragangliomas/pheocromocytomas are rare endocrine tumours, which can be sporadic or familial. During many years their coexistence in the same individual was considered a coincidental finding. However, an association between these two entities was recently demonstrated, with the possible involvement of SDHx genes.
We describe a 57-year-old female patient, who was under surveillance since 1997 for a malignant paraganglioma with vertebral bone metastasis, and harboured a germline frameshift mutation in exon 6 of SDHB gene [c.587-591DelC]. Seventeen years later, she was diagnosed with acromegaly and underwent transesphenoidal endoscopic resection of a somatotropinoma. Three months after surgery she started treatment with lanreotide for residual disease. Despite initial good response, she developed resistance to first generation of somatostatin analogues and treatment had to be switched to pegvisomant. In the immunohistochemical staining, the pituitary adenoma was positive for SDHA expression, while SDHB showed an heterogeneous staining pattern, with areas markedly positive and others with positive and negative cells.
Our findings provide useful data for understanding the link between paragangliomas/pheocromocytomas and somatotropinomas. While we confirm the well-established link between SDHB mutations and paragangliomas/pheocromocytomas, particularly with malignant paragangliomas, the preservation-at least partially-of SDHB expression in the somatotropinoma tissue does not allow drawing definite conclusions about the involvement of the SDHB mutation in pituitary adenoma.
垂体腺瘤和副神经节瘤/嗜铬细胞瘤是罕见的内分泌肿瘤，可为散发或家族性。多年来，它们在同一患者中的共存被认为是偶然发现。然而，最近证实了这两种实体之间存在关联，可能涉及 SDHx 基因。
我们描述了一位 57 岁女性患者，她于 1997 年因恶性副神经节瘤伴椎骨转移而接受监测，携带 SDHB 基因外显子 6 中框移突变[c.587-591DelC]。17 年后，她被诊断为肢端肥大症，并接受了经蝶窦内镜下生长激素腺瘤切除术。术后 3 个月，她开始接受兰瑞肽治疗残留疾病。尽管最初反应良好，但她对第一代生长抑素类似物产生了耐药性，不得不改用培维索孟。在免疫组织化学染色中，垂体腺瘤对 SDHA 表达呈阳性，而 SDHB 表现出不均匀的染色模式，有些区域明显阳性，有些区域阳性和阴性细胞混合存在。
我们的发现为理解副神经节瘤/嗜铬细胞瘤和生长激素腺瘤之间的联系提供了有用的数据。虽然我们证实了 SDHB 突变与副神经节瘤/嗜铬细胞瘤之间的明确关联，特别是与恶性副神经节瘤之间的关联，但在生长激素腺瘤组织中至少部分保留 SDHB 表达，不能得出关于 SDHB 突变参与垂体腺瘤的明确结论。
