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SDHA-related phaeochromocytoma and paraganglioma: review and clinical management - PubMed

  • ️Mon Jan 01 2024

Review

. 2024 Sep 21;31(10):e240111.

doi: 10.1530/ERC-24-0111. Print 2024 Oct 1.

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Review

SDHA-related phaeochromocytoma and paraganglioma: review and clinical management

Adam I Kaplan et al. Endocr Relat Cancer. 2024.

Abstract

Phaeochromocytomas and paragangliomas (collectively termed PPGL) are rare yet highly heritable neuroendocrine tumours, with over one-third of cases associated with germline pathogenic variants (PVs) in numerous genes. PVs in the succinate dehydrogenase subunit-A gene (SDHA) were initially implicated in hereditary PPGL in 2010, and SDHA has since become an important susceptibility gene accounting for up to 2.8% of cases. However, it remains poorly understood, particularly regarding the clinical nature of SDHA PPGL, rates of recurrence and metastasis, and the nature of metastatic disease. We present a narrative review of SDHA-related PPGL, covering pathophysiology, relevance to current clinical practice, and considerations for clinical genetics. We analyse a pool of 107 previously reported cases of SDHA-associated PPGL to highlight the spectrum of SDHA-related PPGL. Our analysis demonstrates that SDHA PPGL occurs across a wide age range (11-81 years) and affects men and women equally. SDHA PPGL typically presents as single tumours (91%), usually occurring in the head and neck (46%) or abdomen (43%, including 15% with phaeochromocytomas). Metastatic disease was reported in 25.5% of cases, with bone (82%) and lymph nodes (71%) being the most common sites of metastasis, often identified many years after the initial diagnosis. A family history of SDHA-related neoplasia was rare, reported in only 4% of cases. Understanding the clinical nature and risks associated with SDHA PVs is essential for facilitating the optimal management of patients and their families.

Keywords: SDHA; hereditary; neoplastic syndromes; paraganglioma; pathogenic variant; phaeochromocytoma; pseudohypoxia; succinate dehydrogenase subunit-A.

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Conflict of interest statement

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Figures

Figure 1
Figure 1

Distribution of PPGL disease in the pooled patient cohort.

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