A 34-year-old woman presents with episodic headache, sweating, and palpitations. Her 24-hour urine shows elevated metanephrines. CT scan reveals a 3.5 cm right adrenal mass. She also has a past history of medullary thyroid carcinoma. Which genetic mutation should be tested first?

• A VHL gene mutation
• B RET proto-oncogene mutation (MEN2A) ✓
• C SDHB mutation
• D NF1 gene mutation

Explanation

The combination of pheochromocytoma and medullary thyroid carcinoma (MTC) is the hallmark of Multiple Endocrine Neoplasia type 2A (MEN2A), caused by activating mutations in the RET proto-oncogene. In MEN2A, pheochromocytoma occurs in ~50% and is almost always benign and bilateral; MTC is usually the index manifestation. VHL mutations cause pheochromocytoma with clear-cell RCC and hemangioblastomas but not MTC. SDHB mutations are associated with malignant paraganglioma. NF1 causes neurofibromatosis-associated pheochromocytoma but not MTC.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.