A 45-year-old woman with confirmed pheochromocytoma (elevated plasma metanephrines) has a 2 cm mass on CT abdomen. To exclude extra-adrenal pheochromocytoma (paraganglioma) and assess for metastatic disease before surgery, which is the most appropriate next investigation?

## Functional Imaging in Pheochromocytoma: MIBG Scintigraphy **Key Point:** MIBG scintigraphy is the gold-standard functional imaging modality for detecting extra-adrenal pheochromocytomas (paragangliomas) and assessing for metastatic disease in confirmed pheochromocytoma. ### Why MIBG Scintigraphy? **High-Yield:** MIBG (metaiodobenzylguanidine) is a norepinephrine analog that is selectively taken up by chromaffin cells via the norepinephrine transporter (NET). It has: - High sensitivity (80–90%) for detecting pheochromocytomas and paragangliomas - Excellent specificity for neuroendocrine tumors - Ability to detect extra-adrenal tumors (paragangliomas in bladder, organ of Zuckerkandl, carotid bifurcation, etc.) - Capacity to identify skeletal and hepatic metastases - Whole-body imaging capability **Clinical Pearl:** MIBG scintigraphy is particularly valuable in: - Familial pheochromocytoma syndromes (MEN 2A/2B, NF1, SDH mutations) where multiple or extra-adrenal tumors are more common - Detecting metastatic pheochromocytoma (10% of cases) - Assessing for recurrence post-operatively ### Diagnostic Imaging Algorithm for Confirmed Pheochromocytoma ```mermaid flowchart TD A[Biochemically confirmed pheochromocytoma]:::outcome --> B[Anatomical localization: CT or MRI abdomen/pelvis]:::action B --> C{Adrenal mass found?}:::decision C -->|Yes, unilateral| D[MIBG scintigraphy]:::action C -->|No or bilateral| E[MIBG scintigraphy]:::action D --> F{Extra-adrenal tumor or metastases?}:::decision E --> G{Extra-adrenal tumor or metastases?}:::decision F -->|Yes| H[Modify surgical plan or consider systemic therapy]:::action F -->|No| I[Proceed to adrenalectomy]:::action G -->|Yes| J[Modify surgical plan or consider systemic therapy]:::action G -->|No| K[Proceed to adrenalectomy]:::action ``` ### Comparison of Functional Imaging Modalities | Modality | Mechanism | Sensitivity | Specificity | Best Use | Limitations | |----------|-----------|-------------|-------------|----------|-------------| | MIBG scintigraphy | Norepinephrine analog uptake via NET | 80–90% | Excellent | Detecting extra-adrenal tumors, metastases, whole-body screening | Requires 24-hour imaging; lower spatial resolution | | FDG-PET | Glucose metabolism | 70–85% | Moderate | Detecting aggressive/metastatic tumors; SDH-mutant tumors | Less specific for pheochromocytoma; uptake in benign lesions | | Octreotide scintigraphy | Somatostatin receptor binding | 50–70% | Moderate | Neuroendocrine tumors (carcinoid, gastrinoma) | Lower sensitivity for pheochromocytoma; not first-line | | MRI with DWI | Anatomical detail + diffusion | High for anatomy | Moderate for function | Assessing adrenal anatomy; detecting cystic/hemorrhagic changes | Limited ability to detect extra-adrenal tumors; no functional assessment | **Warning:** FDG-PET should NOT be used as the primary functional imaging modality for pheochromocytoma. While it may detect aggressive or metastatic tumors, it has lower specificity and may show uptake in benign lesions. MIBG is the standard. ## Role of Other Investigations ### Positron Emission Tomography (FDG-PET) FDG-PET may be used as an adjunct in: - Detecting metastatic pheochromocytoma (especially SDH-mutant tumors, which are more aggressive) - Assessing for malignancy when MIBG is negative However, it is NOT the first-line functional imaging modality. ### MRI with Diffusion-Weighted Imaging MRI is excellent for anatomical characterization of the adrenal mass (T2 hyperintensity, hemorrhage, cystic changes) but does NOT assess for extra-adrenal tumors or metastases as effectively as MIBG. It is a complementary imaging modality, not a replacement for MIBG. ### Octreotide Scintigraphy Octreotide targets somatostatin receptors and is better suited for other neuroendocrine tumors (carcinoid, gastrinoma, insulinoma). It has lower sensitivity for pheochromocytoma and is not recommended. **Mnemonic:** **MIBG for METASTASES** — MIBG scintigraphy is the functional imaging of choice for detecting metastatic pheochromocytoma and extra-adrenal tumors.