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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.
Pheochromocytomas and paragangliomas are tumours of adrenaline-producing tissue that cause dangerous blood pressure surges. Surgery after careful blood-pressure blockade cures most, genetic testing finds an inherited cause in nearly half, and for the minority that spread there are now radioactive drugs that home to the tumour and, since 2025, the first oral targeted pill, belzutifan.
PPGL are catecholamine-secreting tumours of the adrenal medulla (pheochromocytoma) or extra-adrenal sympathetic and parasympathetic paraganglia. They have the highest heritability of any human tumour: about 40 percent carry germline mutations in one of more than 15 genes, grouped into cluster 1 (pseudohypoxia: SDHA/B/C/D, VHL, FH, EPAS1) and cluster 2 (kinase signalling: RET, NF1, TMEM127, MAX). SDHB carriers have the highest metastatic risk. Diagnosis rests on plasma free or urinary fractionated metanephrines, then anatomical imaging and functional imaging with 68Ga-DOTATATE PET (most sensitive for SDHx and metastatic disease) or 18F-FDOPA. Endocrine Society guidance recommends germline testing for every patient.
Surgery after 7 to 14 days of alpha-adrenergic blockade is curative for localised disease, with cortical-sparing adrenalectomy in hereditary bilateral cases. Metastatic disease is treated to control catecholamine excess and tumour burden: 177Lu-DOTATATE for SSTR-positive tumours (NCCN-listed; prospective trials ongoing), high-specific-activity 131I-MIBG (iobenguane I-131, Azedra; FDA 2018, though the manufacturer later announced its commercial discontinuation), cyclophosphamide-vincristine-dacarbazine or temozolomide chemotherapy (particularly SDHB-mutant), and sunitinib, which improved progression-free survival versus placebo in the randomised FIRSTMAPPP trial (Lancet 2024). Belzutifan, the HIF-2alpha inhibitor first approved for VHL-associated tumours, received FDA approval on 14 May 2025 for locally advanced, unresectable or metastatic PPGL in patients aged 12 and older on the basis of the LITESPARK-015 cohort (objective response rate 26 percent), the first oral therapy approved for the disease and a direct hit on the pseudohypoxia biology of cluster 1 tumours.
| Setting | Approach | Guideline |
|---|---|---|
| Localised, secreting | Alpha-blockade (phenoxybenzamine or doxazosin) for 7 to 14 days, volume expansion, then laparoscopic or open adrenalectomy; cortical-sparing surgery in hereditary bilateral disease. | not mapped |
| All patients | Germline genetic testing and, for carriers, lifelong biochemical and imaging surveillance; cascade testing of relatives. | not mapped |
| Metastatic or unresectable | Belzutifan (FDA May 2025, LITESPARK-015); 177Lu-DOTATATE for SSTR-positive disease; 131I-MIBG where available; sunitinib (FIRSTMAPPP); CVD or temozolomide chemotherapy for rapidly progressive or SDHB-mutant disease; alpha-blockade throughout. | NCCN Category 2A |