Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127)
Prepared with OnCo (onco.cc/prep/hereditary-ppgl/). Orientation, not medical advice; your team knows your case.
My details
What I know, what is unclear, changes to discuss
Saved in this browserMy questions
17 on the sheet- 1.What is my exact diagnosis, stage, and grade, and which tests established them?
- 2.Which biomarkers have been tested on my tumour (for example Germline panel testing, Plasma free or urinary fractionated metanephrines, SDHB immunohistochemistry, 68Ga-DOTATATE PET, Tumour size, extra-adrenal site and SDHB status as metastatic risk factors), and what were the results?
- 3.Which subtype is my cancer, and does that change the recommended treatment?
- 4.Is germline (inherited) genetic testing recommended for me or my family?
- 5.For my situation (genetic diagnosis), which of the standard options do you recommend and why?
- 6.For my situation (biochemical and imaging work-up), which of the standard options do you recommend and why?
- 7.For my situation (adrenal tumours in vhl and men2), which of the standard options do you recommend and why?
- 8.For my situation (head and neck paragangliomas), which of the standard options do you recommend and why?
- 9.For my situation (surveillance of carriers), which of the standard options do you recommend and why?
- 10.For my situation (advanced disease in carriers), which of the standard options do you recommend and why?
- 11.Am I a candidate for Belzutifan, Lutetium-177 dotatate, and what side effects should I expect?
- 12.How do the results of Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL apply to someone like me?
- 13.Are there clinical trials I could join, for example of Belzutifan, Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL, Lutetium-177 dotatate, Peptide receptor radionuclide therapy (PRRT)?
- 14.Would a second opinion at a high-volume centre change anything, and can you help arrange it?
- 15.What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?
- 16.I read that “Penetrance of SDHx mutations is incomplete and variable, so how intensively to screen carriers is debated”. How does that affect my plan?
- 17.I read that “No treatment prevents new tumours in carriers”. How does that affect my plan?
The words I may hear
- SDH deficiency (SDHB immunohistochemistry loss): Loss of the succinate dehydrogenase enzyme, shown by a negative SDHB stain, marks a small family of tumours (some stomach GISTs, paragangliomas and phaeochromocytomas, a rare kidney cancer) that are often inherited, occur in young people, ignore imatinib and grow slowly; the stain is the trigger for germline testing of the whole family.
- Adrenalectomy: Removing an adrenal gland.
- Hereditary cancer syndromes: About 5-10% of cancers arise from an inherited gene fault.
- Rare cancers: Rare cancers are those with fewer than about 6 new cases per 100,000 people per year.
Tests and results to bring
Genetic diagnosis: Germline panel testing offered to every patient; SDHB immunohistochemistry on tumour tissue; cascade testing of relatives with genetic counselling.
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.
Biomarker results to ask for: Germline panel testing (SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, RET, NF1, MAX, TMEM127, FH, EPAS1), Plasma free or urinary fractionated metanephrines (noradrenergic pattern in cluster 1), SDHB immunohistochemistry (loss indicates any SDHx mutation), 68Ga-DOTATATE PET (somatostatin receptor expression, staging and radioligand eligibility), Tumour size, extra-adrenal site and SDHB status as metastatic risk factors, Surveillance whole-body MRI in carriers.
Scans and tests linked to this cancer: Active surveillance, CT (computed tomography), Germline (hereditary) testing, MRI, Somatostatin receptor PET (68Ga/64Cu-DOTATATE).
Bring copies of scan reports, pathology and blood results, and a list of every medicine and supplement.
The treatments I may be offered
- Adrenal tumours in VHL and MEN2: Alpha-blockade then cortical-sparing (partial) adrenalectomy to preserve adrenal function given the risk of bilateral disease. (Adrenalectomy, Robotic & minimally invasive surgery)
- Head and neck paragangliomas: Observation for small asymptomatic tumours; surgery or fractionated or stereotactic radiotherapy when growing or symptomatic, weighing cranial nerve risk. (Active surveillance, IMRT / IGRT (modern external beam), SBRT / SABR (stereotactic radiotherapy))
- 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. (Belzutifan, Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL, Lutetium-177 dotatate, Peptide receptor radionuclide therapy (PRRT))
- 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). (MRI, Germline (hereditary) testing)
From the standard of care recorded for this cancer; which apply depends on your stage and biomarkers. Ask which the team recommends and why.