Pheochromocytoma and Paraganglioma Diagnostics and Management

Pheochromocytomas and paragangliomas are rare neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or extra-adrenal paraganglia, respectively. Both entities secrete catecholamines—principally adrenaline and noradrenaline—leading to episodic hypertension, headache, sweating and palpitations. Around 30–40% of cases harbour germline mutations in susceptibility genes, notably those encoding subunits of succinate dehydrogenase (SDH), while others arise sporadically through somatic alterations such as ATRX or TERT promoter mutations. Early and accurate diagnosis relies on biochemical assays of plasma free metanephrines or 24-hour urinary catecholamine metabolites, complemented by cross-sectional imaging (CT, MRI) and targeted functional imaging (for example 68Ga-DOTATATE PET/CT, 131I-MIBG scintigraphy). Genetic screening using next-generation sequencing panels is now standard in many centres. Surgical resection remains the cornerstone of treatment, with pre-operative alpha-adrenergic blockade to mitigate catecholamine surge. Advanced or metastatic disease may be managed with radiolabelled therapies such as high-specific-activity 131I-MIBG, peptide receptor radionuclide therapy, or emerging targeted agents guided by molecular profiling. Prognostication is enhanced by molecular and immunogenomic markers, including tumour mutational burden, microsatellite instability and immune microenvironment characterisation. International consensus guidelines inform surveillance of asymptomatic mutation carriers, optimising timing of biochemical and imaging follow-up to detect tumours at an early, treatable stage. Ongoing efforts aim to refine personalised management pathways by integrating genetic, histopathological and functional imaging data to improve outcomes and quality of life for patients worldwide.

Research from Nature Portfolio

In 2023, comprehensive genomic and immunomic profiling of metastatic pheochromocytomas and paragangliomas defined associations between high somatic copy-number alteration burden, microsatellite instability and alterations in ATRX or TERT, establishing novel prognostic signatures. Transcriptomic analyses uncovered a metastatic gene signature centred on CDK1 and revealed an immunosuppressive microenvironment in most metastatic tumours, with implications for immunotherapy stratification. An international consensus published in 2021 standardised initial screening and ongoing surveillance of asymptomatic carriers of SDHx mutations, harmonising recommendations on the age of first testing, biochemical assays and imaging modalities. This consensus promotes early detection of hereditary tumours and uniform follow-up protocols across paediatric and adult populations, reducing practice variability and enabling prospective outcome studies.

Pheochromocytoma and Paraganglioma Diagnostics and Management publication trend

The graph below shows the total number of articles in pheochromocytoma and paraganglioma diagnostics and management across all publications each year (not limited to Nature Index journals).

Technical terms

Chromaffin cells: Neuroendocrine cells in adrenal medulla that synthesise and secrete catecholamines.

Catecholamines: Hormones (adrenaline, noradrenaline) involved in stress response and cardiovascular regulation.

Metanephrines: Metabolic breakdown products of catecholamines measured in plasma or urine for diagnosis.

Next-generation sequencing (NGS): High-throughput DNA sequencing technology enabling rapid analysis of multiple susceptibility genes.

Immunohistochemistry: Laboratory technique for detecting specific proteins in tissue sections using labelled antibodies.

Tumour microenvironment: Network of non-malignant cells, extracellular matrix and immune elements surrounding a tumour.

131I-MIBG therapy: Targeted radiotherapy using iodine-131 labelled meta-iodobenzylguanidine that binds to catecholamine-producing cells.

SDHx genes: Genes encoding succinate dehydrogenase subunits (SDHA, SDHB, SDHC, SDHD) implicated in hereditary tumour predisposition.

References

1. Genomic and immune landscape Of metastatic pheochromocytoma and paraganglioma. Nature Communications (2023).
2. International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers. Nature Reviews Endocrinology (2021).
3. TOP2A Expression in Pheochromocytoma and Abdominal Paraganglioma: a Marker of Poor Clinical Outcome?. Endocrine Pathology (2023).
4. Efficacy and Safety of High-Specific-Activity 131I-MIBG Therapy in Patients with Advanced Pheochromocytoma or Paraganglioma. Journal of Nuclear Medicine (2018).