The first 60 days: Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127)
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. Below, week by week, is what OnCo's record of Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127) says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
- Genetic diagnosisEndocrine Society clinical practice guideline 2014; NCCN Neuroendocrine and Adrenal Tumors
Germline panel testing offered to every patient; SDHB immunohistochemistry on tumour tissue; cascade testing of relatives with genetic counselling.
- Biochemical and imaging work-upEndocrine Society clinical practice guideline 2014; NCCN Neuroendocrine and Adrenal Tumors
Plasma or urinary metanephrines; CT or MRI; 68Ga-DOTATATE PET as the preferred functional scan for SDHx and other cluster 1 disease.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- PathologistNamed in the standard of care for: Genetic diagnosis, Head and neck paragangliomas, Surveillance of carriers.
- RadiologistNamed in the standard of care for: Biochemical and imaging work-up, Surveillance of carriers.
- SurgeonNamed in the standard of care for: Adrenal tumours in VHL and MEN2, Head and neck paragangliomas.
- Medical oncologistNamed in the standard of care for: Head and neck paragangliomas, Advanced disease in carriers.
- Clinical oncologist (radiotherapy)Named in the standard of care for: Head and neck paragangliomas, Advanced disease in carriers.
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
- 1.Adrenal tumours in VHL and MEN2Endocrine Society clinical practice guideline 2014; NCCN Neuroendocrine and Adrenal Tumors
Alpha-blockade then cortical-sparing (partial) adrenalectomy to preserve adrenal function given the risk of bilateral disease.
- 2.Head and neck paragangliomasEndocrine Society clinical practice guideline 2014; NCCN Neuroendocrine and Adrenal Tumors
Observation for small asymptomatic tumours; surgery or fractionated or stereotactic radiotherapy when growing or symptomatic, weighing cranial nerve risk.
- 3.Advanced disease in carriersEndocrine Society clinical practice guideline 2014; NCCN Neuroendocrine and Adrenal Tumors
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.
- 4.Surveillance of carriersEndocrine Society clinical practice guideline 2014; NCCN Neuroendocrine and Adrenal Tumors
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).
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Everything else follows from an accurate stage and subtype.
- 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?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include SDHB-related paraganglioma, SDHD-related head and neck paraganglioma, SDHC, SDHA and SDHAF2-related paraganglioma.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Genetic diagnosis
- For my situation (genetic diagnosis), which of the standard options do you recommend and why?Guideline options include: Germline panel testing offered to every patient; SDHB immunohistochemistry on tumour tissue; cascade testing of relatives with genetic counselling.
Biochemical and imaging work-up
- For my situation (biochemical and imaging work-up), which of the standard options do you recommend and why?Guideline options include: Plasma or urinary metanephrines; CT or MRI; 68Ga-DOTATATE PET as the preferred functional scan for SDHx and other cluster 1 disease.
Adrenal tumours in VHL and MEN2
- For my situation (adrenal tumours in vhl and men2), which of the standard options do you recommend and why?Guideline options include: Alpha-blockade then cortical-sparing (partial) adrenalectomy to preserve adrenal function given the risk of bilateral disease.
Head and neck paragangliomas
- For my situation (head and neck paragangliomas), which of the standard options do you recommend and why?Guideline options include: Observation for small asymptomatic tumours; surgery or fractionated or stereotactic radiotherapy when growing or symptomatic, weighing cranial nerve risk.
Surveillance of carriers
- For my situation (surveillance of carriers), which of the standard options do you recommend and why?Guideline options include: 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).
Advanced disease in carriers
- For my situation (advanced disease in carriers), which of the standard options do you recommend and why?Guideline options include: 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.
- Am I a candidate for Belzutifan, Lutetium-177 dotatate, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- 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?Trial populations differ from individual patients; ask how closely you match.
Any stage
- 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)?Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Supportive care improves quality of life and helps patients complete treatment.
- 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?Open problems are where trials and second opinions matter most.
- I read that “No treatment prevents new tumours in carriers”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127): the full pageHereditary 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.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- 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.
Every term links to the glossary.