A 42-year-old man with a history of hypertension for 8 years presents with recurrent episodes of severe headache, chest pain, and diaphoresis, each lasting 20–30 minutes. His baseline blood pressure is 160/100 mmHg, but during attacks it rises to 220/140 mmHg. Biochemical workup confirms elevated plasma free metanephrines and 24-hour urine metanephrines. CT abdomen reveals a 3.5 cm left adrenal mass with heterogeneous enhancement and no distant metastases. Genetic testing shows a pathogenic mutation in the SDH-B gene. Which of the following is the most appropriate next step in management?

Explanation

## SDH-B Mutation and Pheochromocytoma: Aggressive Phenotype ### Genetic Context: SDH-B is a High-Risk Gene **Key Point:** SDH-B (succinate dehydrogenase subunit B) mutations confer a significantly elevated risk of malignant pheochromocytoma (30–70% malignancy rate) and multifocal/bilateral disease compared to sporadic or other hereditary forms. This is the most aggressive genetic subtype. **High-Yield:** SDH-B-mutated pheochromocytomas are classified as "paraganglioma syndrome type 4" and carry the highest propensity for: - Metastatic disease (bone, liver, lung, lymph nodes) - Bilateral adrenal involvement - Extra-adrenal paragangliomas - Recurrence after surgery **Mnemonic: SDH-B = MALIGNANT** — **M**alignancy risk 30–70%, **A**ggressive behavior, **L**arge at diagnosis, **I**nvasive/infiltrative, **G**enetic counseling mandatory, **N**eed extensive staging, **A**lways rule out metastases, **N**on-adrenal sites, **T**horough follow-up. ### Staging Before Surgery in SDH-B Mutation **Clinical Pearl:** In SDH-B-mutated pheochromocytoma, comprehensive staging with both anatomical imaging (CT chest/abdomen/pelvis) and functional imaging (MIBG scintigraphy or PET-CT) is mandatory before surgery to: 1. Detect occult metastatic disease 2. Identify bilateral adrenal involvement 3. Detect extra-adrenal paragangliomas 4. Guide surgical extent (unilateral vs. bilateral adrenalectomy) ### Comparison of Genetic Subtypes | Gene | Malignancy Rate | Bilateral Risk | Extra-adrenal | Metastatic Pattern | Screening Urgency | |------|-----------------|-----------------|---------------|-------------------|------------------| | **SDH-B** | **30–70%** | **High** | **Common** | **Bone, liver, lung** | **Highest** | | VHL | 10–20% | 10–20% | Rare | Rare | High | | RET | 5% | 50% | Rare | Rare | High | | NF1 | 5–10% | <5% | Rare | Rare | Moderate | | SDHA | <5% | <5% | Rare | Rare | Moderate | ### Management Algorithm for SDH-B Pheochromocytoma ```mermaid flowchart TD A[SDH-B mutation confirmed<br/>Pheochromocytoma diagnosed]:::outcome --> B[Comprehensive staging required]:::action B --> C[CT chest/abdomen/pelvis<br/>+ MIBG scintigraphy]:::action C --> D{Metastatic disease<br/>or bilateral adrenal?}:::decision D -->|Yes| E[Multidisciplinary discussion<br/>Consider neoadjuvant therapy]:::action D -->|No| F[Genetic counseling<br/>Screen first-degree relatives]:::action F --> G[Initiate alpha-blockade<br/>phenoxybenzamine]:::action G --> H[Add beta-blocker if needed]:::action H --> I[Adrenalectomy after<br/>blood pressure control]:::action I --> J[Lifelong biochemical<br/>and imaging surveillance]:::action ``` **Key Point:** Genetic counseling and screening of first-degree relatives is mandatory in all SDH-B carriers, as 50% of relatives will inherit the mutation. However, this does NOT delay surgical planning—it occurs in parallel with staging and preoperative optimization. ### Preoperative Preparation (Alpha-Blockade) **High-Yield:** Alpha-blockade with phenoxybenzamine (non-selective, irreversible) or doxazosin (selective, reversible) is essential before surgery to prevent intraoperative hypertensive crisis. Beta-blockers are added only AFTER adequate alpha-blockade to prevent unopposed alpha-mediated vasoconstriction. **Clinical Pearl:** The sequence is critical: **Alpha first, then Beta.** Starting beta-blockers without alpha-blockade causes paradoxical hypertension due to unopposed alpha-adrenergic effects. [cite:Harrison 21e Ch 405]