Biochemically Silent Abdominal Paragangliomas in Patients with Mutations in the Succinate Dehydrogenase Subunit B Gene
Biochemically Silent Abdominal Paragangliomas in Patients with Mutations in the Succinate Dehydrogenase Subunit B Gene
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DOI：
10.1210/jc.2008-1093
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发表时间：
2008-12-01
影响因子：
5.8
通讯作者：
Eisenhofer, Graeme
中科院分区：
文献类型：
--
作者：
Timmers, Henri J. L. M.;Pacak, Karel;Eisenhofer, Graeme
内容：肾上腺和肾上腺外腹部副神经节瘤（PGL）患者的血浆和尿液中的肾上腺素（儿茶酚胺的O-甲基化代谢物）浓度几乎总是升高。我们报告4例生化沉默的腹部PGL，其中metanephrines是正常的，尽管广泛的diseases.Objective：我们的目的是确定的机制缺乏的儿茶酚胺分泌过多和代谢metanephrines在生化沉默的PGL.Design：这是一个描述性研究。患者：一个索引病例和三个额外的患者与大腹部PGL和转移，但缺乏证据的儿茶酚胺生产，6例转移性儿茶酚胺生产PGL和突变的琥珀酸脱氢酶亚单位B（SDHB）基因，和136例随机患者与儿茶酚胺生产PGL纳入研究。血浆，尿液和肿瘤组织中的儿茶酚胺和代谢产物的浓度进行了计算，电子显微镜和酪氨酸羟化酶免疫组化。结果：所有四名患者的生化沉默PGL有一个潜在的SDHB突变。在指示病例中，肿瘤组织中的儿茶酚胺浓度（1.8 nmol/g）小于136例产生儿茶酚胺的肿瘤患者的中位数（20，410 nmol/g）的0.01%。电子显微镜显示，在所有四个生化沉默PGLs的正常分泌颗粒的存在下。酪氨酸羟化酶免疫反应性是可以忽略不计的四个生化沉默PGLs，但丰富的儿茶酚胺生产PGLs.Conclusions：SDHB突变的患者可能会出现生化沉默的腹部PGLs由于缺乏酪氨酸羟化酶导致的儿茶酚胺合成缺陷。SDHB突变患者的肿瘤筛查不应仅限于儿茶酚胺过量的生化试验。（临床内分泌代谢杂志93：4826-4832，2008）
Context: Patients with adrenal and extra-adrenal abdominal paraganglioma (PGL) almost invariably have increased plasma and urine concentrations of metanephrines, the O-methylated metabolites of catecholamines. We report four cases of biochemically silent abdominal PGL, in which metanephrines were normal despite extensive disease.Objective: Our objective was to identify the mechanism underlying the lack of catecholamine hypersecretion and metabolism to metanephrines in biochemically silent PGL.Design: This is a descriptive study.Setting: The study was performed at a referral center. Patients: One index case and three additional patients with large abdominal PGL and metastases but with the lack of evidence of catecholamine production, six patients with metastatic catecholamine-producing PGL and a mutation of the succinate dehydrogenase subunit B (SDHB) gene, and 136 random patients with catecholamine-producing PGL were included in the study.Main Outcome Measures: Plasma, urine, and tumor tissue concentrations of catecholamines and metabolites were calculated with electron microscopy and tyrosine hydroxylase immunohistochemistry.Results: All four patients with biochemically silent PGL had an underlying SDHB mutation. In the index case, the tumor tissue concentration of catecholamines (1.8 nmol/g) was less than 0.01% that of the median (20,410 nmol/g) for the 136 patients with catecholamine-producing tumors. Electron microscopy showed the presence of normal secretory granules in all four biochemically silent PGLs. Tyrosine hydroxylase immunoreactivity was negligible in the four biochemically silent PGLs but abundant in catecholamine-producing PGLs.Conclusions: Patients with SDHB mutations may present with biochemically silent abdominal PGLs due to defective catecholamine synthesis resulting from the absence of tyrosine hydroxylase. Screening for tumors in patients with SDHB mutations should not be limited to biochemical tests of catecholamine excess. (J Clin Endocrinol Metab 93: 4826-4832, 2008)