A 42-year-old woman from Mumbai is referred after incidental discovery of a 2.5 cm right adrenal mass on CT abdomen done for abdominal pain. She has a history of medullary thyroid carcinoma (MTC) diagnosed 3 years ago, treated with total thyroidectomy. Serum calcitonin is 180 pg/mL (normal <10). Plasma metanephrines are elevated: normetanephrine 1.8 nmol/L (normal <0.9). Genetic testing shows a RET M918T mutation. What is the next step in management?

Explanation

## Clinical Diagnosis: MEN 2A with Pheochromocytoma **Key Point:** This patient has **MEN 2A** (RET proto-oncogene mutation, M918T variant): **MTC + pheochromocytoma ± primary hyperparathyroidism**. The adrenal mass with elevated plasma metanephrines confirms **pheochromocytoma**. This is a **catecholamine-secreting tumour** — uncontrolled surgery risks **hypertensive crisis and arrhythmias**. **High-Yield:** In pheochromocytoma, **α-blockade MUST precede β-blockade**. Never give beta-blockers alone (unopposed α-adrenergic stimulation → hypertensive crisis). Adequate blockade (typically 7–14 days) is mandatory before surgery. ### Management Algorithm for Pheochromocytoma in MEN 2A ```mermaid flowchart TD A[MEN 2A + Pheochromocytoma Confirmed]:::outcome --> B[Alpha-Blockade First]:::action B --> C[Phenoxybenzamine or Doxazosin]:::action C --> D[Target: Supine BP < 160/90, HR < 100]:::decision D -->|Adequate| E[Add Beta-Blocker]:::action E --> F[Labetalol or Selective Beta-Blocker]:::action F --> G[Wait 7-14 Days for Stabilization]:::action G --> H[Adrenalectomy]:::action H --> I[Intraoperative Monitoring: ECG, BP, Catecholamines]:::action A --> J[Screen for MTC Recurrence]:::action J --> K[Calcitonin, CEA, Imaging]:::action ``` ### Why This Answer 1. **Elevated plasma metanephrines** confirm catecholamine excess → pheochromocytoma is real and symptomatic. 2. **Unopposed catecholamine release during surgery** causes hypertensive crisis, MI, arrhythmias, and death if not blocked. 3. **Phenoxybenzamine** (non-selective, irreversible α-blocker) is the gold standard; titrate until BP and HR controlled. 4. **Beta-blockade** (propranolol or labetalol) only after adequate α-blockade to prevent reflex tachycardia and hypertension. 5. **Adrenalectomy** is definitive and indicated in MEN 2A pheochromocytoma (risk of malignancy ~10–15%). **Clinical Pearl:** Intraoperative **sudden catecholamine surge** during tumour manipulation can cause flash pulmonary oedema, stroke, or MI. Adequate preoperative blockade reduces perioperative mortality from ~30% to <3%. **Mnemonic:** **ALPHA before BETA** — Remember: **A**lpha **B**efore **B**eta = ABB rule. [cite:Harrison 21e Ch 397; Robbins 10e Ch 24]