A 42-year-old woman with a family history of medullary thyroid carcinoma is found to have a 3 cm left adrenal mass on imaging. Plasma free metanephrines are elevated (3.8 nmol/L). Serum calcitonin is normal. She is hemodynamically stable on phenoxybenzamine and atenolol. What is the most appropriate next step in management?

Explanation

## Syndromic Pheochromocytoma — Genetic Screening Is Mandatory **Key Point:** A patient with pheochromocytoma AND a family history of medullary thyroid carcinoma (MTC) has a high likelihood of **MEN-2 syndrome** (RET mutation). Genetic testing for RET proto-oncogene mutations and thyroid screening are essential before surgery to identify occult MTC and plan comprehensive management. ## MEN-2 and Pheochromocytoma Association **High-Yield:** Approximately **50% of pheochromocytomas are hereditary**, and **MEN-2A/2B accounts for ~5% of all pheochromocytomas**. The presence of: - Pheochromocytoma - Family history of MTC - Young age at presentation ...strongly suggests MEN-2 syndrome. ## Why Genetic Testing Before Surgery? | Finding | Implication | Action | |---------|-------------|--------| | RET mutation positive | MEN-2 syndrome confirmed | Thyroid ultrasound ± calcitonin stimulation test; prophylactic thyroidectomy if indicated | | Occult MTC present | Risk of metastatic disease | Modify surgical approach; consider combined adrenalectomy + thyroidectomy | | Normal calcitonin but RET+ | Early MTC or preclinical | Annual surveillance; prophylactic thyroidectomy per guidelines | | RET mutation negative | Sporadic pheochromocytoma | Standard adrenalectomy alone | **Clinical Pearl:** Calcitonin can be normal in early MTC. RET mutation status is more sensitive for identifying MEN-2 carriers than calcitonin alone. ## Management Algorithm for Syndromic Pheo ```mermaid flowchart TD A[Pheo + FHx MTC]:::outcome --> B{RET mutation testing}:::decision B -->|Positive| C[MEN-2 syndrome]:::outcome C --> D[Thyroid ultrasound<br/>+ calcitonin stimulation]:::action D --> E{MTC detected?}:::decision E -->|Yes| F[Combined adrenalectomy<br/>+ thyroidectomy]:::action E -->|No| G[Adrenalectomy<br/>+ surveillance]:::action B -->|Negative| H[Sporadic pheo]:::outcome H --> I[Standard left<br/>adrenalectomy]:::action ``` **Mnemonic:** **MEN-2 Pheo Rule** = **M**edullary thyroid cancer in family → **E**xamine **N**uclear mutations (RET) → **2** Tumors to screen (adrenal + thyroid).