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Risk of metastatic pheochromocytoma and paraganglioma in SDHx mutation carriers: a systematic review and updated meta-analysis
  1. Hansong Lee1,
  2. Seongdo Jeong1,
  3. Yeuni Yu1,
  4. Junho Kang1,
  5. Hokeun Sun2,
  6. Je-Keun Rhee3,
  7. Yun Hak Kim4
  1. 1Interdisciplinary program of genomic data science, Pusan National University School of Medicine, Yangsan, Korea (the Republic of)
  2. 2Department of Statistics, Pusan National University School of Medicine, Busan, Korea (the Republic of)
  3. 3School of Systems Biomedical Science, Soongsil University, Seoul, Korea (the Republic of)
  4. 4Department of Anatomy and Department of Biomedical Informatics, Pusan National University School of Medicine, Yangsan, Korea (the Republic of)
  1. Correspondence to Professor Yun Hak Kim, Anatomy and Biomedical Informatics, Pusan National University School of Medicine, Yangsan, Korea (the Republic of); yunhak10510{at}


Background Pheochromocytoma and paraganglioma (PPGL) are tumours that arise from chromaffin cells. Some genetic mutations influence PPGL, among which, those in genes encoding subunits of succinate dehydrogenase (SDHA, SDHB, SDHC and SDHD) and assembly factor (SDHAF2) are the most relevant. However, the risk of metastasis posed by these mutations is not reported except for SDHB and SDHD mutations. This study aimed to update the metastatic risks, considering prevalence and incidence of each SDHx mutation, which were dealt formerly all together.

Methods We searched EMBASE and MEDLINE and selected 27 articles. The patients included in the studies were divided into three groups depending on the presence of PPGL. We checked the heterogeneity between studies and performed a meta-analysis using Hartung-Knapp-Sidik-Jonkman method based on a random effect model.

Results The highest PPGL prevalence was for SDHB mutation, ranging from 23% to 31%, and for SDHC mutation (23%), followed by that for SDHA mutation (16%). The lowest prevalence was for SDHD mutation, ranging from 6% to 8%. SDHAF2 mutation showed no metastatic events. The PPGL incidence showed a tendency similar to that of its prevalence with the highest risk of metastasis posed by SDHB mutation (12%–41%) and the lowest risk by SDHD mutation (~4%).

Conclusion There was no integrated evidence of how SDHx mutations are related to metastatic PPGL. However, these findings suggest that SDHA, SDHB and SDHC mutations are highly associated and should be tested as indicators of metastasis in patients with PPGL.

  • genetic epidemiology
  • genetic screening/counselling
  • neuro endocrinology
  • pheochromocytoma and paraganglioma
  • SDHx mutation

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  • HL and SJ are joint first authors.

  • HL and SJ contributed equally.

  • Correction notice This article has been corrected since it was published Online First. Contributorship statements have been added to the first page of the article.

  • Contributors Design and conception of study: LH, JS and KYH. Data collection: LH, JS, YY and KJ. Data analysis and interpretation: LH and JS. Writing of manuscript: LH, JS and KYH. Critical review: LH, JS, YY, KJ, SH, RJ and KYH.

  • Funding This study was supported by grants from the Basic Science Research Program (MOE, NRF-2016R1A6A3A11931738) and Collaborative Genome Program for Fostering New Post‐Genome Industry (NRF‐2017M3C9A6047610) through the National Research Foundation of Korea (NRF) grant funded by the Korean government.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.