Pheochromocytoma and paraganglioma – etiology, pathogenesis, and clinical manifestations
Pheochromocytoma: Tumor of chromaffin cells in the adrenal medulla → produces catecholamines (epinephrine, norepinephrine, dopamine).
Paraganglioma: Similar tumor outside adrenal medulla, arising from extra-adrenal sympathetic or parasympathetic paraganglia.
Etiology
Sporadic cases
Majority (~70%).
Familial cases (~30%)
Associated with genetic syndromes:
- Multiple Endocrine Neoplasia (MEN) type 2A and 2B.
- Von Hippel-Lindau (VHL) disease.
- Neurofibromatosis type 1 (NF1).
- SDH gene mutations (succinate dehydrogenase subunit defects).
Pathogenesis
Tumor development
Chromaffin cells (neural crest- derived) become neoplastic.
Tumor autonomously produces and secretes excess catecholamines.
Catecholamine excess effects
- 1 Cardiovascular system:
Increased alpha- adrenergic stimulation → vasoconstriction → hypertension.
Increased beta- adrenergic effects → tachycardia, increased cardiac output.
- 2 Metabolic effects:
Hyperglycemia (due to glycogenolysis and gluconeogenesis).
Lipolysis.
- 3 Other systemic effects:
Sweating, headache, anxiety —from sympathetic overstimulation.
Clinical manifestations
Classic triad
Episodic headache.
Sweating.
Palpitations (tachycardia).
Hypertension
Most common feature.
Can be sustained or paroxysmal (sudden spikes).
Hypertensive crises triggered by:
- Stress.
- Surgery or anesthesia.
- Certain foods (cheese, wine —high in tyramine).
- Certain drugs (beta- blockers without alpha blockade).
Other symptoms
Pallor.
Tremor.
Anxiety or panic attacks.
Weight loss.
Hyperglycemia signs (polydipsia, polyuria).
Paragangliomas
Similar symptoms if functional (sympathetic paragangliomas).
Non-functional paragangliomas (especially parasympathetic, e.g., carotid body) usually present as painless neck mass.
Possible complications
Cardiomyopathy (catecholamine- induced).
Arrhythmias.
Stroke.
Multi- organ failure during hypertensive crisis.
Summary Table