Catecholamine burden and germline genotype independently predict cardiovascular phenotype in phaeochromocytoma and paraganglioma  — ASN Events
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  3. Catecholamine burden and germline genotype independently predict cardiovascular phenotype in phaeochromocytoma and paraganglioma 

Catecholamine burden and germline genotype independently predict cardiovascular phenotype in phaeochromocytoma and paraganglioma  (#341)

Li Yi Wang 1 , Roderick J Clifton-Bligh 1 2 , Elizabeth Bernard 1 3 , David Chan 1 4 , Matti L Gild 1 2
  1. Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia
  2. Department of Endocrinology and Diabetes, Royal North Shore Hospital, St Leonards, NSW, Australia
  3. Department of Nuclear Medicine, Royal North Shore Hospital, St Leonards, NSW, Australia
  4. Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW, Australia

Phaeochromocytoma and paraganglioma (PPGL) are heterogeneous neuroendocrine tumours that cause cardiovascular morbidity through catecholamine excess. Germline pathogenic variants in SDHx genes, particularly SDHB, are associated with worse prognosis [1]. This study examined the cardiovascular manifestations of PPGL and their clinical, biochemical, genetic and imaging predictors.  

Patients who underwent surgical resection for PPGL at Royal North Shore Hospital between 2000 and 2025 were identified from the Endocrine Surgical Database; of 254 patients, 121 with complete clinical, biochemical, and follow-up data were included. Of these, 87 patients underwent baseline 68Ga-DOTATATE PET/CT, allowing extraction of semi-quantitative parameters: maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion activity (TLA). Predictors of cardiovascular-dominant presentation (composite of any catecholamine-related symptoms, hypertension, or major cardiovascular event) were assessed using univariable and multivariable regression, adjusting for pathogenic germline variant status, plasma normetanephrine, and tumour size. Progression-free survival (PFS) was compared by SDHx status using log-rank testing.  

Cardiovascular-dominant presentation was present in 72 patients (59.5%), more commonly in phaeochromocytoma than paraganglioma (65.4% vs 23.5%; P = 0.002). In multivariable regression (n = 86), higher plasma normetanephrine was associated with greater odds of cardiovascular-dominant presentation (adjusted OR, 1.32 per 1,000 pmol/L increase; P = 0.005), whereas pathogenic germline variant status was associated with lower odds (adjusted OR, 0.17; P = 0.006). MTV and TLA were higher in cardiovascular-dominant presentation on univariable analysis (P = 0.014 and 0.013, respectively). Paraganglioma was independently associated with lower MTV and TLA. SDHx variant carriers had shorter PFS than non-carriers (log-rank P = 0.003).  

Cardiovascular-dominant presentation in PPGL was most strongly associated with catecholamine burden, independent of volumetric PET parameters.  Its lower frequency among germline variant carriers may reflect earlier detection via genetic screening. Paraganglioma was associated with lower volumetric PET burden, while SDHx status remained prognostic, reinforcing genotype-informed surveillance. 

  1. Lee, H., et al., Risk of metastatic pheochromocytoma and paraganglioma in SDHx mutation carriers: a systematic review and updated meta-analysis. J Med Genet, 2020. 57(4): p. 217-225.