Phaeochromocytoma

Phaeochromocytoma is often referred to as a '10% tumour': 10% are malignant, 10% are bilateral, 10% are extra-adrenal (paragangliomas), and 10% are familial. Though rare, it is a critical cause of secondary hypertension that can lead to fatal hypertensive crises. The tumour secretes excessive amounts of adrenaline (epinephrine) and noradrenaline (norepinephrine). While many cases are sporadic, up to 30-40% are associated with genetic syndromes, including Multiple Endocrine Neoplasia type 2 (MEN 2A and 2B), Von Hippel-Lindau (VHL) disease, and Neurofibromatosis type 1 (NF1). The diagnosis relies on biochemical evidence of catecholamine excess, typically via plasma or 24-hour urine metanephrines. Localisation is initially performed with CT or MRI, followed by functional imaging (e.g., MIBG scan). The definitive treatment is surgical excision, but this is high-risk because handling the tumour can cause massive catecholamine release. Thus, pre-operative management with alpha-blockade (e.g., phenoxybenzamine) followed by beta-blockade is mandatory.

The adrenal medulla is an extension of the sympathetic nervous system. Chromaffin cells convert the amino acid tyrosine into dopamine, noradrenaline, and adrenaline. In phaeochromocytoma, the autonomous secretion of these catecholamines leads to overstimulation of alpha-1, alpha-2, beta-1, and beta-2 adrenergic receptors. Alpha-1 stimulation causes peripheral vasoconstriction (severe hypertension). Beta-1 stimulation causes increased heart rate and contractility (palpitations, tachycardia). The metabolism of catecholamines involves the enzymes COMT and MAO, which produce metanephrines and vanillylmandelic acid (VMA). Metanephrines are more stable in the circulation and are therefore the preferred diagnostic marker.

The presentation is notoriously variable. The most common feature is hypertension (80-90%). Paroxysms ('spells') occur in about 50% of patients and are characterized by a sudden onset of: 1. Severe headache; 2. Palpitations and tachycardia; 3. Profuse diaphoresis (sweating); 4. Anxiety or a 'sense of doom'; 5. Pallor (due to vasoconstriction). Spells can be triggered by abdominal pressure (palpation), exercise, or certain foods (tyramine-containing). Complications of the 'catecholamine surge' include myocardial infarction, stroke, pulmonary oedema, and cardiac arrhythmias.

Biochemical: 24-hour urinary fractionated metanephrines (two collections) OR plasma free metanephrines (preferred if high clinical suspicion). Imaging: CT Abdomen or MRI (both highly sensitive for the adrenals). Functional Imaging: 123I-MIBG scintigraphy (used if CT/MRI are negative or to look for extra-adrenal/metastatic disease). Genetic testing: Offered to all patients, especially if young or with bilateral disease.

Medical (Pre-operative): 1. Alpha-blockade: Phenoxybenzamine (irreversible alpha-blocker) or Doxazosin. This must be started first to prevent a hypertensive crisis. 2. Beta-blockade: Propranolol or Atenolol. Only start AFTER alpha-blockade; otherwise, 'unopposed alpha-stimulation' will cause a massive rise in BP. 3. Fluid resuscitation: To prevent postural hypotension as the vascular bed expands. Surgical: Laparoscopic adrenalectomy is the gold standard. Intensive intra-operative monitoring (usually with arterial line) is required. Acute Crisis: Phentolamine IV (short-acting alpha-blocker) and Nitroprusside.