Phaeochromocytoma — the alpha-before-beta rule and the catecholamine crisis

Diagnosis: phaeochromocytoma until proven otherwise. The classic triad of episodic headache, sweating and palpitations with hypertension, the striking pallor during spells, and an orthostatic drop are highly suggestive. The adrenal mass with high unenhanced attenuation (~42 HU) and slow washout on CT is the radiological signature of a phaeochromocytoma. The diagnosis is biochemical first, anatomical second.^[1]

Diagnostic strategy — biochemistry before biopsy.^[1]

• First line: plasma free metanephrines (or 24-hour urine fractionated metanephrines and catecholamines). Metanephrine/normetanephrine are produced continuously inside the tumour, so they are far more sensitive than the parent catecholamines.
• Stop interfering drugs before testing — tricyclic antidepressants, phenoxybenzamine, decongestants, caffeine, MAOIs — to avoid false positives.
• If biochemistry is equivocal, use the clonidine suppression test (a phaeo fails to suppress).
• Localise with CT or MRI (already done here); for extra-adrenal, metastatic, hereditary or large tumours add functional imaging — MIBG scintigraphy or 18F-DOPA / 68Ga-DOTATATE PET.
• Offer genetic testing (SDHx, RET, VHL, NF1, MAX, TMEM127) — over 30 percent of patients carry a germline mutation.
• CRITICAL: never biopsy an unblocked adrenal mass with raised metanephrines — it precipitates a fatal catecholamine crisis.

Preoperative preparation — the cardinal rule: ALPHA before BETA.^[1][2]

• Phenoxybenzamine (a non-competitive, irreversible alpha-blocker) 10 mg twice daily, titrate up every 2 to 3 days over 10 to 14 days to about 1 mg/kg/day, until seated blood pressure is around 130/80 with a mild orthostatic drop and nasal congestion appears (a clinical sign of adequate blockade).
• Volume expansion with a high-salt diet and IV saline — chronic vasoconstriction has left the patient volume-depleted.
• Only then add a beta-blocker (propranolol or bisoprolol) for reflex tachycardia — never first.
• Goals: normotension, no orthostatic syncope, moderate tachycardia controlled; then proceed to laparoscopic adrenalectomy.
• Why alpha first? A beta-blocker given alone leaves alpha-1-mediated vasoconstriction unopposed, producing a catastrophic hypertensive crisis.

Intra-operative hypertensive crisis.^[2]

• On tumour handling, catecholamine surge causes severe hypertension (often >200 systolic).
• Give IV phentolamine (short-acting alpha-blocker) boluses/infusion, or sodium nitroprusside or nicardipine infusion.
• Treat arrhythmia with a short-acting beta-blocker (esmolol) only after alpha-blockade is established.
• After tumour vessels are clamped, anticipate hypotension (sudden loss of catecholamines on a fully blocked, vasodilated patient) — give IV fluids and vasopressors (noradrenaline/phenylephrine); watch for hypoglycaemia (loss of catecholamine-driven hyperglycaemia) — monitor glucose.
• Intensive care post-operatively for haemodynamic and glucose monitoring.