New Insights into the Clinical Characterization of SDHAF2-related Familial Paraganglioma Syndrome.

IF 5.1 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Journal of Clinical Endocrinology & Metabolism Pub Date : 2025-10-16 DOI:10.1210/clinem/dgaf149

Antia Fernandez-Pombo, Zulema Nogareda-Seoane, Jose Manuel Cameselle-Teijeiro, Ana Ecenarro-Montiel, Cecilia Vieira-Leite, Gemma Rodriguez-Carnero, Noelia Otero-Mato, Virginia Pubul-Nuñez, Marcos Pazos-Couselo, Lourdes Loidi, Jose Manuel Cabezas-Agricola

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引用次数: 0

Abstract

Background: The clinical characterization of SDHAF2-related familial paraganglioma syndrome remains elusive. The aim of this study is to contribute to the knowledge of this syndrome with valuable new information.

Methods: A total of 56 individuals with the p.(Gly78Arg) variant in the SDHAF2 gene were prospectively evaluated. Of the 33 subjects who developed paragangliomas (PGLs)/pheochromocytomas (PCs) throughout follow-up, clinical, biochemical, and imaging data were collected. [68Ga]Ga-DOTA-TOC and [18F]DOPA positron emission tomography/computed tomography (PET/CT) scans were carried out on a subset of 22 patients with PGLs/PCs to compare their accuracy; surgical specimens (n = 13) were microscopically evaluated to elucidate their potential malignant behavior.

Results: Of the 33 patients (58.9%) with SDHAF2-related tumors, 17 (51.5%) were women, with a mean age at diagnosis of 38.6 ± 17.2 years. Tumor development was found to be inherited paternally in all subjects. All the patients evaluated except 1 showed head and neck PGLs. Eleven patients (33.3%) showed mediastinal and abdominal extra-adrenal PGLs and 2 patients presented PCs. Multifocality was observed in 26 subjects (78.8%). Sixteen patients (48.5%) were asymptomatic at diagnosis. Only 4 patients with PGLs/PCs showed normetanephrine or 3-methoxytyramine secretion. Metastatic disease was observed in 2 patients (6.1%). Grading System for Adrenal Pheochromocytoma and Paraganglioma score was ≥3 in 84.6% of tumors and Pheochromocytoma of the Adrenal Gland Scaled Score was ≥4 in 69.2%. [68Ga]Ga-DOTA-TOC PET/CT showed a greater detection rate (95.7%) of multifocal PGLs and metastatic lesions than [18F]DOPA PET/CT (79.3%), as well as higher mean maximum standardized uptake value.

Conclusion: The current study offers new insights into the phenotypic characterization of SDHAF2-related paraganglioma syndrome including the development of extra-cervical PGLs and metastatic transformation.

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sdhaf2相关家族副神经节瘤综合征临床特征的新见解

背景：与sdhaf2相关的家族性副神经节瘤综合征的临床特征尚不明确。本研究的目的是为该综合征的认识提供有价值的新信息。方法：对56例SDHAF2基因p.（Gly78Arg）变异个体进行前瞻性评估。在随访期间发生副神经节瘤(PGLs)/嗜铬细胞瘤（pc）的33例受试者中，收集临床、生化和影像学资料。[68Ga]Ga-DOTA-TOC和[18F]DOPA PET/CT扫描22例PGLs/PCs患者，比较其准确性，并对手术标本（n=13）进行显微评估，以阐明其潜在的恶性行为。结果：33例（58.9%）sdhaf2相关肿瘤患者中，17例（51.5%）为女性，平均诊断年龄为38.6±17.2岁。在所有的研究对象中，肿瘤的发展都是父系遗传的。除1例外，其余患者均出现头颈部pgl。11例（33.3%）出现纵隔和腹部肾上腺外pgl， 2例出现pc。多焦性26例（78.8%）。16例（48.5%）患者在诊断时无症状。只有4例pgl /PCs患者出现去甲肾上腺素或3-甲氧基酪胺分泌。2例患者出现转移性疾病（6.1%）。84.6%的肿瘤GAPP评分≥3分，69.2%的肿瘤PASS评分≥4分。[68Ga]Ga-DOTA-TOC PET/CT对多灶性pgl和转移灶的检出率（95.7%）高于[18F]DOPA PET/CT(79.3%)，且平均SUVmax更高。结论：目前的研究为sdhaf2相关副神经节瘤综合征的表型特征提供了新的见解，包括宫颈外pgl的发展和转移转化。

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来源期刊

Journal of Clinical Endocrinology & Metabolism 医学-内分泌学与代谢

CiteScore

11.40

自引率

5.20%

发文量

673

审稿时长

1 months

期刊介绍： The Journal of Clinical Endocrinology & Metabolism is the world"s leading peer-reviewed journal for endocrine clinical research and cutting edge clinical practice reviews. Each issue provides the latest in-depth coverage of new developments enhancing our understanding, diagnosis and treatment of endocrine and metabolic disorders. Regular features of special interest to endocrine consultants include clinical trials, clinical reviews, clinical practice guidelines, case seminars, and controversies in clinical endocrinology, as well as original reports of the most important advances in patient-oriented endocrine and metabolic research. According to the latest Thomson Reuters Journal Citation Report, JCE&M articles were cited 64,185 times in 2008.