Succinate dehydrogenase-related PPGL: Clinical and Genetic Insights from Indian Study

Objective Data on Succinate dehydrogenase-related pheochromocytoma and paraganglioma ( SDHx PPGL) in India is 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 done for clinical, imaging, genetics 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 SDHAF2 c.232G>A mutation (paternal inheritance), and 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. 68 Ga-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 10 novel SDHx gene mutations. Surgical treatment was performed in 67.3% of cases, and systemic radiotherapy was utilized in advanced cases, achieving stable disease in most cases. Conclusion In this largest Indian cohort of SDHx PPGL, high metastatic burden, SDHB dominance, and novel gene variants were noted.