Key Facts

Phaeochromocytoma is rare but potentially fatal if undiagnosed. The key clinical challenge is diagnosis — consider in any patient with episodic symptoms or resistant hypertension. Alpha-blockade before surgery is mandatory to prevent life-threatening perioperative complications.

Epidemiology

Incidence ~2-8 per million/year. Peak age 30-50 years. ~0.2-0.6% of hypertensive patients. ~5% of incidentally discovered adrenal masses.

Aetiology

~60-70% sporadic. ~30-40% hereditary: MEN2A/2B (RET mutation), Von Hippel-Lindau (VHL mutation), SDH mutations (SDHA/B/C/D — paraganglioma syndromes), NF1. All patients with phaeochromocytoma should have genetic testing.

Pathophysiology

Excessive catecholamine secretion (noradrenaline predominantly in adrenal; noradrenaline in extra-adrenal paraganglioma) → episodic or sustained hypertension, tachycardia, vasoconstriction. Catecholamines metabolised to metanephrines (normetanephrine, metanephrine) — these are more stable and better for biochemical diagnosis.

Classic Triad (Episodic — Minutes to Hours)

• Headache (severe, pounding)
• Sweating (profuse diaphoresis)
• Palpitations (tachycardia)
• ± Anxiety, tremor, pallor (NOT flushing)

Hypertension

• Paroxysmal (~50%): dramatic BP spikes (>200/120 mmHg) with intervening normotension
• Sustained (~50%): with or without paroxysms
• Resistant hypertension: uncontrolled despite ≥3 antihypertensives

Other

• Weight loss
• Hyperglycaemia (catecholamine-mediated glycogenolysis)
• Postural hypotension (paradoxical — chronic vasoconstriction → reduced plasma volume)
• Cardiomyopathy (catecholamine-induced — Takotsubo-like)

Red Flags

• Hypertensive crisis triggered by anaesthesia, surgery, drugs (beta-blockers without alpha-cover, metoclopramide, TCAs)
• Adrenal incidentaloma → always check metanephrines
• Family history of MEN2, VHL, SDH mutations

Biochemical

• Plasma free metanephrines: most sensitive test (~97%); normetanephrine and metanephrine; sample after 30 minutes supine rest
• 24-hour urine metanephrines and catecholamines: alternative; high specificity
• Chromogranin A: elevated (non-specific)

Imaging (After Biochemical Confirmation)

• CT/MRI adrenals: localise tumour; typically >3 cm, high signal on T2 MRI, enhancing
• ¹²³I-MIBG scintigraphy: functional imaging; confirms catecholamine-producing tumour; detects extra-adrenal/metastatic disease
• ⁶⁸Ga-DOTATATE PET/CT: superior for SDH-related paragangliomas and metastatic disease
• ¹⁸F-FDG PET/CT: for suspected metastatic disease

Genetic Testing

• All patients: screen for RET (MEN2), VHL, SDHB/C/D, NF1
• SDHB mutations: highest malignancy risk (~30-70%)

Other

• Blood glucose (hyperglycaemia), calcium/PTH (MEN2A → hyperparathyroidism)
• If MEN2: calcitonin (medullary thyroid cancer)

Pre-Operative Preparation (Essential)

1. Alpha-blockade first: phenoxybenzamine 10mg BD (titrate to 1-2mg/kg/day; target BP <130/80 seated, >90 mmHg standing) or doxazosin 2-16mg/day; start ≥10-14 days before surgery
2. Liberal salt and fluid intake: expand plasma volume (counteract chronic vasoconstriction-induced hypovolaemia)
3. Beta-blocker ONLY after adequate alpha-blockade (usually 2-3 days pre-op): propranolol 20-40mg TDS or atenolol — for tachycardia control
4. NEVER beta-block without alpha-cover → unopposed alpha stimulation → hypertensive crisis

Surgery

• Laparoscopic adrenalectomy: curative for benign localised disease (>90%)
• Perioperative: close BP monitoring; IV phentolamine for hypertensive crisis; volume replacement for post-resection hypotension

Post-Operative

• Monitor for hypotension (loss of catecholamine drive) and hypoglycaemia
• Check metanephrines at 2-4 weeks → should normalise
• Annual biochemical surveillance lifelong (10% recurrence)

Malignant/Metastatic

• ¹³¹I-MIBG therapy (therapeutic radioiodine)
• Chemotherapy: cyclophosphamide/vincristine/dacarbazine (CVD)
• Targeted therapies: sunitinib

Referral Criteria

• Endocrinology/endocrine surgery: all confirmed phaeochromocytoma
• Clinical genetics: all patients (genetic testing)
• Oncology: metastatic disease

Benign phaeochromocytoma: >90% cure rate with surgery. 5-year survival after surgery ~95%. Malignant phaeochromocytoma (~10-15%): 5-year survival ~50%. SDHB mutations: highest malignancy risk. Annual surveillance essential — recurrence rate ~10%. Untreated: risk of hypertensive crisis, stroke, MI, death. Paraganglioma: higher malignancy rate than adrenal phaeochromocytoma.

Hereditary Phaeochromocytoma Syndromes

Alpha-Blockade Protocol