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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Hereditary pheochromocytoma and paraganglioma is the inherited form of these adrenaline-producing tumours, caused by a fault in one of more than a dozen genes, most often SDHB, SDHD, VHL and RET. Knowing the gene changes care: SDHB carriers have the highest risk of spread, VHL and MEN2 patients get adrenal-sparing surgery because tumours arise on both sides, and relatives are screened.
Pheochromocytomas (adrenal) and paragangliomas (sympathetic chain, head and neck) have the strongest hereditary basis of any tumour type: germline mutations are found in 30 to 40 percent of patients, in the succinate dehydrogenase genes (SDHB, SDHD, SDHC, SDHA and SDHAF2), VHL, RET (MEN2), NF1, MAX, TMEM127, FH and others, and the Endocrine Society guideline recommends that all patients be offered testing. The genes fall into two clusters that shape the tumour: cluster 1 (SDHx, VHL, FH, EPAS1) tumours are pseudohypoxic, noradrenergic or non-secreting, often extra-adrenal and multiple, and express somatostatin receptors strongly; cluster 2 (RET, NF1, MAX, TMEM127) tumours are kinase-driven, adrenergic and usually adrenal. SDHB mutations carry the highest risk of metastasis, SDHD (paternally inherited) causes multiple head and neck paragangliomas, VHL and MEN2 cause bilateral pheochromocytomas alongside their other tumours, and SDHx carriers are also at risk of gastrointestinal stromal tumours, renal cell carcinoma and pituitary adenomas.
Management differs from sporadic disease at every step. Diagnosis rests on plasma or urinary metanephrines and, for non-secreting head and neck tumours, imaging; SDHB immunohistochemistry on the tumour flags an SDHx mutation, and 68Ga-DOTATATE PET is the preferred whole-body scan for cluster 1 disease because of its somatostatin receptor expression. Surgery follows alpha-blockade, and in VHL and MEN2 a cortical-sparing adrenalectomy is preferred to avoid lifelong steroid dependence after bilateral tumours; head and neck paragangliomas, which rarely secrete and grow slowly, are often watched or irradiated rather than resected because surgery risks the cranial nerves. Carriers enter lifelong surveillance with annual metanephrines and periodic whole-body MRI from childhood in SDHB and SDHD families, and cascade testing is offered to relatives. For carriers who develop advanced disease, the HIF-2 alpha inhibitor belzutifan, approved for VHL-associated tumours in 2021 and for advanced pheochromocytoma and paraganglioma in 2025, exploits the pseudohypoxia pathway directly, and radioligand therapy with lutetium-177 dotatate suits the somatostatin-receptor-rich cluster 1 tumours. The genetics also guide prognosis: metastatic risk, multiplicity and the chance of a second primary all follow the gene.
| Setting | Approach | Guideline |
|---|---|---|
| Genetic diagnosis | Germline panel testing offered to every patient; SDHB immunohistochemistry on tumour tissue; cascade testing of relatives with genetic counselling. | not mapped |
| Biochemical and imaging work-up | Plasma or urinary metanephrines; CT or MRI; 68Ga-DOTATATE PET as the preferred functional scan for SDHx and other cluster 1 disease. | not mapped |
| Adrenal tumours in VHL and MEN2 | Alpha-blockade then cortical-sparing (partial) adrenalectomy to preserve adrenal function given the risk of bilateral disease. | not mapped |
| Head and neck paragangliomas | Observation for small asymptomatic tumours; surgery or fractionated or stereotactic radiotherapy when growing or symptomatic, weighing cranial nerve risk. | not mapped |
| Surveillance of carriers | Annual metanephrines and clinical review from childhood, with whole-body MRI every two to three years in SDHB and SDHD carriers; screening for associated tumours (GIST, renal cell carcinoma, pituitary). | not mapped |
| Advanced disease in carriers | Belzutifan (approved for VHL-associated tumours 2021 and for advanced pheochromocytoma and paraganglioma 2025); lutetium-177 dotatate for somatostatin-receptor-positive disease; see the metastatic record. | not mapped |