Conditions · Metabolism (biochemistry)
Hereditary paraganglioma and pheochromocytoma (SDH) !
Some families inherit changes in succinate dehydrogenase that cause tumours in the neck and the adrenal glands.
Updated 2026-10-31
Structures involved
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In biochemistry
- Krebs cycle: Step 6 · Succinate dehydrogenase (complex II)
- Malate–aspartate shuttle: Step 2 · 2-Oxoglutarate/malate carrier (OGC, SLC25A11)
- Succinate dehydrogenase (complex II)
- Catecholamines: synthesis and breakdown
- FAD (flavin adenine dinucleotide)
- Oncogenes and tumour suppressor genes
- Warburg effect (aerobic glycolysis in cancer)
In embryology
Why it happens
What it is
Tumours of the paraganglia (carotid body, vagus nerve, sympathetic chain) and the adrenal medulla caused by germline variants in the succinate dehydrogenase genes (SDHA, SDHB, SDHC, SDHD, SDHAF2).
Who gets it
About one third of paragangliomas and pheochromocytomas are inherited. Carotid paraganglioma is more common in people living at high altitude, as in the Andes.
Causes
- A variant in an SDH gene inherited from one parent (autosomal dominant)
- SDHD and SDHAF2: the tumour usually appears only if the variant comes from the father
Risk factors
- Relatives with paraganglioma or pheochromocytoma
- Multiple tumours or a young age
- Living at high altitude (carotid body)
Pathophysiology
Without succinate dehydrogenase, succinate builds up and inhibits the enzymes that break down hypoxia-inducible factor (HIF). The cell reacts as if short of oxygen: vessels and cells grow. That is why succinate is called an 'oncometabolite'.
Symptoms and signs
- A painless lump on the side of the neck
- Episodes of headache, sweating and palpitations (if the tumour secretes catecholamines)
- High blood pressure that is hard to control
- Hoarseness, hearing loss or pulsatile tinnitus (head and neck tumours)
Diagnosis
- Clinical
- Suspect inheritance with multiple, young, extra-adrenal tumours or affected relatives.
- Tests
- Plasma free or 24-hour urine metanephrines; genetic testing of the SDH genes; SDHB immunohistochemistry of the tumour.
- Imaging
- CT or MRI to locate; DOTATATE PET (somatostatin analogue) for multiple tumours and metastases.
Treatment
- Medical
- Alpha and then beta blockade before operating on a catecholamine-secreting tumour
- Surgical
- Surgical removal of the tumour
- Procedure
- Radiotherapy or radionuclide therapy in selected cases
- Follow-up
- Lifelong surveillance with biochemistry and imaging for carriers
Complications
- Hypertensive crisis
- Metastasis (mainly SDHB)
- Cranial nerve injury from the tumour or the surgery
Test yourself
Think of the answer, then tap the question to see it.
Why is succinate called an oncometabolite?
When it builds up it blocks HIF breakdown, creating pseudohypoxia that favours tumours.
Which SDH gene carries the highest risk of metastasis?
SDHB.
Which biochemical test comes first?
Plasma free metanephrines or 24-hour urine metanephrines.
Related conditions
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Hereditary paraganglioma-pheochromocytoma: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); SDHB gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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