Succinate Dehydrogenase-Related Pheochromocytoma and Paraganglioma (SDHx-Ppgl): Clinical and Genetic Insights From an Indian Study

Authors

• Ketki Sunil Ambulkar
• Anima Sharma
• Vijaya Sarathi
• Saba Samad Memon
• Anurag Ranjan Lila
• Rohit Barnabas
• Manjiri Karlekar
• Virendra Patil
• Samiksha Hegisthe
• Gwendolyn Fernandes
• Sameer Rege
• Gaurav Malhotra
• Hemangini Thakkar
• Nalini S Shah
• Tushar R Bandgar

Language

English

Publication Date

10-1-2025

Journal

Endocrine Connections

DOI

10.1530/EC-25-0500

PMID

40981001

PMCID

PMC12508308

PubMedCentral® Posted Date

10-6-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Objective: Data on succinate dehydrogenase-related pheochromocytoma and paraganglioma (SDHx PPGL) in India are limited. We describe the clinical and genetic characteristics of SDHx PPGL from a single center in western India.

Design, patients, and measurements: A retrospective review of SDHx PPGL patients was performed for clinical, imaging, genetic, and treatment details.

Results: Among 46 patients (39 probands, 24 males), the median age at diagnosis was 32.5 (IQR: 23-41) years. We report the youngest patient with SDHC (age 8 years). SDHB mutations were the most prevalent (24/39 probands), followed by SDHD, SDHC, SDHA, and SDHAF2. We report the first Indian family with the SDHAF2 c.232G>A mutation (paternal inheritance) and the index patient with metastasis. Paraganglioma (PGL) (single or multiple) was common (80%), followed by pheochromocytoma (11%) and multifocal PPGL (9%). sPGL predominated in the SDHB cohort (80.6%), whereas multiple/multifocal PPGLs were common in others. Biochemically silent tumors were noted in 26% patients. 68Ga-DOTATATE PET/CT was the most sensitive imaging modality. The prevalence of metastasis was high in patients with SDHB variants (51.7%) but was also substantial in those with other SDHx genes (29.4%). Most probands harbored unique variants, and we report ten novel SDHx gene mutations. Surgical treatment was performed in 67.3% cases, and systemic radiotherapy was utilized in advanced cases, achieving stable disease in most cases.

Conclusion: In this largest Indian cohort of SDHx PPGL, a high metastatic burden, SDHB dominance, and novel gene variants were noted.

Keywords

SDHx, PPGL, malignancy, SDHAF2, 68Ga-DOTATATE PET/CT, PRRT

Published Open-Access

yes

Recommended Citation

Ambulkar, Ketki Sunil; Sharma, Anima; Sarathi, Vijaya; et al., "Succinate Dehydrogenase-Related Pheochromocytoma and Paraganglioma (SDHx-Ppgl): Clinical and Genetic Insights From an Indian Study" (2025). Faculty, Staff and Student Publications. 4427.
https://digitalcommons.library.tmc.edu/uthmed_docs/4427