Pheochromocytoma

A 30 year old male with a history of poorly controlled hypertension presents with recurrent episodes of palpitations, severe headache, and profuse sweating over several months. These episodes are sudden in onset, last for minutes, and resolve spontaneously. He also reports anxiety and a sense of impending doom during episodes. On examination, blood pressure is 160/100 mmHg and pulse is 140/min. Laboratory evaluation shows elevated 24 hour urinary fractionated metanephrines. CT scan reveals a right adrenal mass. Diagnosis?

Diagnosis is Pheochromocytoma.

1. Definition

Pheochromocytoma is a catecholamine secreting tumor arising from chromaffin cells of the adrenal medulla. Tumors arising from extra-adrenal chromaffin tissue are called paragangliomas.

2. Etiology

1. Sporadic cases are most common
2. Approximately 30 to 40 percent are hereditary

Associated syndromes include:

1. Multiple endocrine neoplasia type 2 (MEN 2)
2. Von Hippel Lindau syndrome (VHL)
3. Neurofibromatosis type 1 (NF1)
4. Hereditary paraganglioma syndromes (SDH mutations)

3. Pathophysiology

1. Excess secretion of catecholamines
• Norepinephrine causes sustained hypertension
• Epinephrine causes tachycardia, anxiety, and paroxysmal symptoms
2. Catecholamines are metabolized into metanephrines
3. Metanephrines have a longer half-life and are preferred for diagnosis

4. Clinical Features

4.1 Classic Presentation

1. Paroxysmal or sustained hypertension
2. Triad:
• Headache
• Diaphoresis
• Palpitations

4.2 Other Features

1. Tachycardia
2. Anxiety or panic attacks
3. Pallor
4. Weight loss
5. Orthostatic hypotension

4.3 Precipitating Factors

1. Stress
2. Surgery or anesthesia
3. Drugs such as:
• Tricyclic antidepressants
• Metoclopramide
• Glucocorticoids
4. Contrast agents

5. Types

1. Adrenal pheochromocytoma
• Most common
• Secretes epinephrine and norepinephrine
2. Paraganglioma
• Extra-adrenal
• Commonly secretes norepinephrine

6. Diagnosis

6.1 Biochemical Testing

1. Plasma free metanephrines is the most sensitive test
2. 24 hour urinary fractionated metanephrines
3. Preferred over catecholamines due to higher diagnostic accuracy

6.2 Imaging

1. CT abdomen and pelvis after biochemical confirmation
2. MRI if CT contraindicated
3. 123I MIBG scan for localization or metastatic disease
4. PET scan in selected cases

7. Management

7.1 Preoperative Medical Management

1. Alpha adrenergic blockade first
• Phenoxybenzamine or selective alpha-1 blockers
2. Beta blockers only after alpha blockade
• Prevent unopposed alpha stimulation
3. Volume expansion
• High sodium diet and fluids

7.2 Definitive Treatment

1. Surgical resection (adrenalectomy)

8. Complications

1. Hypertensive crisis
2. Arrhythmias
3. Myocardial infarction
4. Stroke
5. Catecholamine induced cardiomyopathy

9. Key Clinical Insight

Episodic headache + sweating + palpitations + resistant hypertension + elevated metanephrines + adrenal mass = Pheochromocytoma

10. Exam Level Pearls

1. Plasma free metanephrines are most sensitive
2. Alpha blockade must precede beta blockade
3. 30 to 40 percent cases are hereditary
4. Paragangliomas are extra adrenal tumors
5. Biopsy is contraindicated due to risk of catecholamine crisis
6. MEN 2 includes pheochromocytoma and medullary thyroid carcinoma
7. Rule of 10s is outdated