Cancer Genetics, Hormones and Cancer Group, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales 2065, Australia.
J Clin Endocrinol Metab. 2013 Jun;98(6):E1103-8. doi: 10.1210/jc.2013-1400. Epub 2013 Apr 30.
Reports of the coexistence of pituitary adenomas and pheochromocytoma/paraganglioma are uncommon. Recently germline mutations in 2 of the genes encoding succinate dehydrogenase, SDHC and SDHD, were associated with pituitary tumors.
Our aim was to determine whether the development of a pituitary adenoma was associated with SDHA mutation.
A 46-year-old female presented with carotid body paraganglioma (proband). Subsequently the proband's son was diagnosed with a nonfunctioning pituitary macroadenoma at age 30 years.
An immunohistochemical analysis of the resected paraganglioma and pituitary adenoma revealed the loss of succinate dehydrogenase subunit B and succinate dehydrogenase subunit A (SDHA) expression in both tumors, with the preservation of staining in nonneoplastic tissue. Mutation analysis showed a novel SDHA mutation (c.1873C>T, p.His625Tyr) in the germline of the proband as well as in the proband's son. In the paraganglioma of the proband, in addition to the germline mutation, a somatic mutation was observed (c.1865G>A, p.Trp622*). In the pituitary adenoma of the proband's son, loss of SDHA immunoreactivity was paradoxically accompanied by loss of the mutant allele.
This is the first report of a pituitary adenoma arising in the setting of germline SDHA mutation. The loss of SDHA protein expression in both the paraganglioma (proband) and pituitary adenoma (proband's son) argues strongly for a causative role of SDHA mutation. This report further strengthens the link between pituitary neoplasia and germline SDH mutation. Although pituitary adenomas appear rare among patients carrying SDH subunit mutations, they may have been underrecognized due to the low penetrance of disease and lack of systematic surveillance.
垂体腺瘤和嗜铬细胞瘤/副神经节瘤共存的报告并不常见。最近，编码琥珀酸脱氢酶的 2 个基因（SDHC 和 SDHD）中的种系突变与垂体肿瘤有关。
我们旨在确定垂体腺瘤的发生是否与 SDHA 突变有关。
一位 46 岁女性因颈动脉体副神经节瘤（先证者）就诊。随后，先证者的儿子在 30 岁时被诊断为无功能垂体大腺瘤。
切除的副神经节瘤和垂体腺瘤的免疫组织化学分析显示，两种肿瘤中琥珀酸脱氢酶亚单位 B 和琥珀酸脱氢酶亚单位 A（SDHA）的表达均缺失，而非肿瘤组织的染色得以保留。突变分析显示，先证者及其儿子的种系中存在新的 SDHA 突变（c.1873C>T，p.His625Tyr）。在先证者的副神经节瘤中，除了种系突变外，还观察到体细胞突变（c.1865G>A，p.Trp622*）。在先证者儿子的垂体腺瘤中，SDHA 免疫反应缺失与突变等位基因缺失同时发生，这令人费解。
这是首例报道的在种系 SDHA 突变背景下发生的垂体腺瘤。先证者的副神经节瘤（proband）和垂体腺瘤（proband 的儿子）中 SDHA 蛋白表达缺失强烈提示 SDHA 突变起致病作用。该报告进一步加强了垂体肿瘤与种系 SDH 突变之间的联系。尽管携带 SDH 亚单位突变的患者中垂体腺瘤似乎罕见，但由于疾病的低外显率和缺乏系统监测，它们可能被低估了。
