What is the recommended approach to evaluate and treat anxiety, panic attacks, insomnia, and depression in a patient with a catecholamine‑producing paraganglioma?

Management of Mental Health Symptoms in Catecholamine-Producing Paraganglioma

The primary approach is to first treat the underlying catecholamine excess with alpha-adrenergic blockade, as anxiety, panic attacks, and related psychiatric symptoms are direct manifestations of catecholamine hypersecretion and will typically resolve with definitive tumor treatment. 1, 2

Initial Evaluation and Recognition

Recognize that psychiatric symptoms are catecholamine-mediated, not primary psychiatric disorders:

• Anxiety, panic attacks, palpitations, sweating, tremors, and apprehension are cardinal manifestations of catecholamine excess from sympathetic paragangliomas 1, 3
• These symptoms mimic primary panic disorder but are caused by direct alpha- and beta-adrenergic receptor stimulation 4, 5
• The classic triad of headache, palpitations, and profuse sweating has 93.8% specificity for catecholamine-producing tumors 2
• Depression and emotional lability have been documented in patients with elevated dopamine from paragangliomas 6, 7

Critical distinction: Head and neck paragangliomas are typically non-secreting (up to 95%), while sympathetic chain paragangliomas usually produce catecholamines 1. Confirm biochemical activity with plasma or urinary metanephrines before attributing symptoms to catecholamine excess 1, 2.

Treatment Algorithm

Step 1: Initiate Alpha-Adrenergic Blockade

For catecholamine-producing tumors with psychiatric symptoms, start alpha-blockade 7-14 days before any definitive intervention:

• Use phenoxybenzamine (non-selective alpha-blocker) or doxazosin (selective alpha-1 blocker) with gradually increasing dosages until blood pressure targets are achieved 1, 2
• Phenoxybenzamine provides less intraoperative hemodynamic instability based on the PRESCRIPT trial 1
• Never initiate beta-blockers before alpha-blockade, as this causes unopposed alpha-stimulation and precipitates severe hypertensive crisis 2, 3
• Add beta-1 selective blockers only after adequate alpha-blockade if tachycardia persists 1

Step 2: Symptomatic Management During Preoperative Period

For acute anxiety and panic symptoms while awaiting surgery:

• Benzodiazepines can be used cautiously for severe anxiety to reduce sympathetic hyperactivity 3
• However, use should be time-limited given abuse potential and cognitive impairment risks 1
• Avoid tricyclic antidepressants as they interfere with catecholamine testing and may worsen hypertension 2

For insomnia related to catecholamine surges:

• Address with adequate alpha-blockade first, as this treats the underlying cause 1
• Short-term benzodiazepines may be considered if insomnia persists despite adequate blockade 1

Step 3: Definitive Treatment

Surgical resection is the treatment of choice and typically resolves psychiatric symptoms:

• Most paragangliomas are benign and can be completely excised 8, 5
• Following successful surgical cure, catecholamine-mediated psychiatric symptoms resolve 8, 4
• Measure plasma or urine metanephrines 8 weeks post-operatively to confirm biochemical cure 1

Step 4: Post-Treatment Psychiatric Assessment

If psychiatric symptoms persist after biochemical cure:

• Reassess 8-12 weeks post-operatively once catecholamine levels normalize 1
• Consider formal psychiatric evaluation for primary anxiety or depressive disorders that may have been masked by catecholamine excess 1
• Use standard psychiatric treatments (SSRIs, cognitive behavioral therapy) if symptoms represent independent psychiatric conditions 1

Special Considerations

For non-secreting paragangliomas (typically head and neck):

• Psychiatric symptoms are unlikely to be catecholamine-mediated 1
• Standard psychiatric evaluation and treatment are appropriate 1
• Medical causes of anxiety (pain, infection, electrolyte imbalance) should be addressed first 1

For dopamine-secreting paragangliomas:

• Elevated dopamine can cause anxiety and depression even without hypertension 6
• Patients may be normotensive or hypotensive despite catecholamine production 1
• Alpha-blockade is not advised for dopamine-only producing tumors 1

Multidisciplinary approach is essential:

• Coordinate care between endocrinology, surgery, anesthesiology, and psychiatry 7, 8
• Establish mental health support at diagnosis, as psychiatric symptoms significantly impact quality of life 7

Critical Pitfalls to Avoid

• Never treat as primary psychiatric disorder without excluding catecholamine excess - this delays definitive treatment and risks life-threatening complications 2, 4
• Never use beta-blockers alone - this is absolutely contraindicated and can be fatal 2, 3
• Never perform biopsy of suspected paraganglioma - this can trigger fatal hypertensive crisis 1, 2
• Never assume psychiatric symptoms are unrelated - up to 50% of paragangliomas are hereditary, and psychiatric manifestations may be the presenting feature 7, 8

Long-Term Follow-Up

Annual biochemical testing is mandatory:

• Assess for recurrence, metastatic disease, or delayed appearance of multiple primary tumors 8, 5
• Lifelong surveillance is required, especially for hereditary cases and SDHB mutations 1, 8
• Monitor for recurrence of psychiatric symptoms as potential indicator of tumor recurrence 7