Management of Hypermetabolic Adrenal Focus with Headache and Episodic Hypertension
This clinical presentation strongly suggests pheochromocytoma, and you must immediately obtain biochemical confirmation with plasma free metanephrines or 24-hour urinary fractionated metanephrines before proceeding with any imaging or intervention. 1
Immediate Biochemical Testing (First Priority)
Plasma free metanephrines are the screening test of choice, with 96-100% sensitivity and 89-98% specificity for pheochromocytoma. 1 This test has superior diagnostic accuracy compared to plasma catecholamines (85% sensitivity) or urinary metanephrines alone (89% sensitivity). 2
Key Testing Considerations:
Order plasma free metanephrines (normetanephrine and metanephrine) as the initial test - a normal result essentially excludes pheochromocytoma with 100% negative predictive value. 2
Alternative acceptable test is 24-hour urinary fractionated metanephrines if plasma testing is unavailable, though this has lower sensitivity. 1, 3
Critical preanalytical factors to avoid false positives: 4
- Patient should be supine and rested for 30 minutes before blood draw
- Discontinue tricyclic antidepressants if possible (can elevate metanephrines up to 4-fold)
- Avoid acetaminophen, which interferes with assays
- Consider that obesity and obstructive sleep apnea can cause mild elevations
Interpretation thresholds: 1
- Values >4-fold upper limit of normal are highly specific for pheochromocytoma
- Values between 1-4 fold require clonidine suppression testing (failure to suppress plasma metanephrines by 40% has 100% specificity and 96% sensitivity)
Imaging Only After Biochemical Confirmation
Do not proceed with anatomical imaging until biochemical evidence confirms a catecholamine-producing tumor. 1 The hypermetabolic focus on imaging alone is insufficient for diagnosis, as many adrenal incidentalomas show increased metabolic activity without being functional.
Once Biochemically Confirmed:
Start with high-resolution CT of the abdomen as first-line anatomical imaging. 1
MRI is preferred if: 1
- Metastatic disease is suspected
- Patient is pregnant or young (radiation exposure concerns)
- Extra-adrenal paraganglioma is suspected
Functional imaging with ¹²³I-MIBG scintigraphy is useful for confirming functionality and detecting metastatic disease. 1, 5
Preoperative Medical Management (Critical for Safety)
All patients with biochemically confirmed pheochromocytoma require alpha-adrenergic blockade before any surgical intervention to prevent hypertensive crisis. 1, 6, 7
Specific Preoperative Protocol:
Initiate phenoxybenzamine (non-selective alpha-blocker) starting 7-14 days before surgery, titrating to control blood pressure and symptoms. 6
Add beta-blocker ONLY AFTER adequate alpha-blockade if tachycardia develops - never use beta-blockers first as this can precipitate hypertensive crisis. 6, 7
High-sodium diet (>5000 mg/day) and aggressive fluid intake for 2-3 days preoperatively to prevent postoperative hypotension from volume contraction. 7
Consider metyrosine (tyrosine hydroxylase inhibitor) as adjunctive therapy if available, particularly for large tumors or those with severe catecholamine excess. 1
Surgical Management
Minimally invasive adrenalectomy is the definitive treatment for confirmed pheochromocytoma once adequate preoperative blockade is achieved. 7
Laparoscopic adrenalectomy is preferred for most adrenal pheochromocytomas <6 cm without local invasion. 1, 7
Open adrenalectomy is indicated for tumors with suspected malignancy, local invasion, or size >6 cm. 1
Intraoperative considerations: Experienced anesthesia team required with arterial line monitoring and availability of short-acting antihypertensives (nitroprusside, nicardipine) and vasopressors. 7
Critical Pitfalls to Avoid
Never biopsy an adrenal mass suspected to be pheochromocytoma - this can precipitate fatal hypertensive crisis. 1
Do not assume normal urinary catecholamines exclude pheochromocytoma - rare cases exist with normal urinary studies but elevated plasma metanephrines. 5
Avoid medications that can trigger catecholamine crisis in unblocked patients: metoclopramide, droperidol, glucagon, corticosteroids, and certain anesthetic agents. 1
Do not use beta-blockers alone - this causes unopposed alpha-stimulation and paradoxical hypertension. 1, 6
Genetic Testing and Long-term Follow-up
Genetic testing should be offered to all patients with confirmed pheochromocytoma, as 32-79% have germline mutations (VHL, RET, NF1, SDHx genes). 3, 7
Lifelong annual biochemical surveillance is required after resection to detect recurrence (10-15% for adrenal pheochromocytoma). 7
Family screening should be performed if germline mutation is identified. 7