Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
Endocr Relat Cancer. 2022 Mar 21;29(4):213-224. doi: 10.1530/ERC-21-0359.
Head and neck paragangliomas (HNPGLs) are tumors of parasympathetic origin that occur at variable locations and are often secondary to germline mutations in succinate dehydrogenase (SDH) subunit genes. Occasionally, these tumors produce catecholamines. Here, we assessed whether different locations of HNPGLs relate to the presence of SDHx mutations, catecholamine production and other presentations. In this multicenter study, we collected clinical and biochemical data from 244 patients with HNPGLs and 71 patients without HNPGLs. We clarified that jugulotympanic HNPGLs have distinct features. In particular, 88% of jugulotympanic HNPGLs arose in women, among whom only 24% occurred due to SDHx mutations compared to 55% in men. Jugulotympanic HNPGLs were also rarely bilateral, were of a smaller size and were less often metastatic compared to carotid body and vagal HNPGLs. Furthermore, we showed that plasma concentrations of methoxytyramine (MTY) were higher (P < 0.0001) in patients with HNPGL than without HNPGL, whereas plasma normetanephrine did not differ. Only 3.7% of patients showed strong increases in plasma normetanephrine. Plasma MTY was positively related to tumor size but did not relate to the presence of SDHx mutations or tumor location. Our findings confirm that increases in plasma MTY represent the main catecholamine-related biochemical feature of patients with HNPGLs. We expect that more sensitive analytical methods will make biochemical testing of HNPGLs more practical in the future and enable more than the current 30% of patients to be identified with dopamine-producing HNPGLs. The sex-dependent differences in the development of HNPGLs may have relevance to the diagnosis, management and outcomes of these tumors.
头颈部副神经节瘤（HNPGL）是起源于副交感神经的肿瘤，发生于不同部位，常继发于琥珀酸脱氢酶（SDH）亚单位基因突变。这些肿瘤偶尔会产生儿茶酚胺。在这里，我们评估了 HNPGL 的不同部位与 SDHx 突变、儿茶酚胺产生和其他表现的关系。在这项多中心研究中，我们收集了 244 例 HNPGL 患者和 71 例无 HNPGL 患者的临床和生化数据。我们明确了鼓室副神经节瘤具有独特的特征。特别是，88%的鼓室副神经节瘤发生在女性中，其中只有 24%是由于 SDHx 突变引起的，而男性则为 55%。鼓室副神经节瘤也很少是双侧的，体积较小，与颈动脉体和迷走神经副神经节瘤相比转移的可能性更小。此外，我们还表明，HNPGL 患者的血浆甲氧基酪胺（MTY）浓度较高（P<0.0001），而血浆去甲肾上腺素浓度则无差异。只有 3.7%的患者表现出强烈的血浆去甲肾上腺素增加。血浆 MTY 与肿瘤大小呈正相关，但与 SDHx 突变的存在或肿瘤位置无关。我们的研究结果证实，血浆 MTY 的增加代表了 HNPGL 患者主要的儿茶酚胺相关生化特征。我们预计，未来更敏感的分析方法将使 HNPGL 的生化检测更加实用，并使目前 30%的多巴胺产生 HNPGL 患者得到识别。HNPGL 发展中的性别差异可能与这些肿瘤的诊断、治疗和预后有关。
