A 29-year-old woman presents with episodic severe headache, sweating, and palpitations. 24-hour urine metanephrines are elevated threefold. MIBG scintigraphy shows uptake in the right adrenal. On genetic testing, she is found to have a germline SDHB mutation. This mutation is associated with which specific risk profile?
- A High risk of extra-adrenal paragangliomas with significantly elevated malignancy risk ✓
- B High risk of bilateral adrenal phaeochromocytomas with low malignant potential
- C RET proto-oncogene-associated MEN2A with medullary thyroid carcinoma
- D VHL syndrome with cerebellar haemangioblastomas and renal cell carcinoma
Correct answer: A. High risk of extra-adrenal paragangliomas with significantly elevated malignancy risk
Explanation
SDHB (succinate dehydrogenase B subunit) mutations are associated with paraganglioma/phaeochromocytoma syndrome type 4. Unlike VHL or RET mutations, SDHB mutations carry the highest malignancy risk (>20-40%) among SDH-related syndromes and predispose to extra-adrenal paragangliomas (carotid body, thoracic, abdominal). VHL mutations associate with haemangioblastoma and renal cell carcinoma, and RET mutations associate with MEN2A. SDHD mutations cause bilateral and head-neck paragangliomas but lower malignancy risk.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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