A 32-year-old woman has resistant hypertension despite triple-drug therapy (amlodipine 10 mg, telmisartan 80 mg, indapamide 2.5 mg). She has paroxysmal headaches, sweating, and palpitations. BP 185/110 mmHg. 24-hour urine shows elevated metanephrines and normetanephrines. CT adrenal is normal, but MIBG scan shows bilateral adrenal uptake. The genetic mutation most commonly associated with bilateral pheochromocytoma is:
- A VHL gene mutation (von Hippel-Lindau disease) ✓
- B RET proto-oncogene (MEN-2A/2B)
- C SDHB mutation (hereditary paraganglioma-pheochromocytoma type 4)
- D SDHD mutation (hereditary PGL-1)
Explanation
Bilateral adrenal pheochromocytoma is most commonly associated with VHL disease (VHL gene on chromosome 3p) or MEN-2 (RET mutations). Among hereditary syndromes, VHL is the most common cause of bilateral pheochromocytoma overall. SDHB mutations are more often associated with extra-adrenal paraganglioma and carry high malignant potential. SDHD mutations (head and neck paraganglioma) are usually maternally imprinted — only paternal transmission is symptomatic. In bilateral adrenal pheo without family history, VHL and RET are the priority genetic tests. Genetic testing is recommended for ALL pheochromocytoma patients.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.