Pheochromocytoma and Paraganglioma
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Direct answer
Alpha-blockade before beta-blockade — that sequence is the core of phaeochromocytoma care: a beta-blocker given first leaves vasoconstricted alpha receptors unopposed and can precipitate a hypertensive crisis. Diagnosis rests on plasma free metanephrines or 24-hour urinary fractionated metanephrines (sensitivity above 95 per cent for plasma), drawn rested and off interfering drugs; CT or MRI localises the tumour, with 123I-MIBG scintigraphy or 68Ga-DOTATATE PET reserved for extra-adrenal, metastatic or syndrome-linked disease. Preoperative preparation runs 7–14 days of phenoxybenzamine with salt and fluid loading, a beta-blocker added only after adequate alpha-blockade, targeting near-normotension with a permissible mild orthostatic drop before laparoscopic adrenalectomy. Roughly 30–40 per cent of cases carry germline mutations (RET, VHL, NF1, SDHx), so genetic testing is now standard in every newly diagnosed patient — the old "rule of tens" is retired.
What you must remember
- Presentation grammar: paroxysmal headache, palpitations and sweating — at least two of the three in most patients; episodes last minutes to an hour; sustained hypertension in about half, and orthostatic hypotension in volume-contracted disease.
- Biochemical ladder: plasma free metanephrines drawn supine after 30 minutes' rest is the most sensitive screen; levels above three to four times the upper limit are essentially diagnostic. Avoid caffeine, paracetamol (older assays), tricyclics and labetalol beforehand.
- Imaging order: contrast CT or MRI first (pheochromocytomas classically hyperintense on T2); functional imaging — MIBG or 68Ga-DOTATATE (superior for SDHx-related and metastatic paraganglioma) — for syndromic, extra-adrenal, recurrent or malignant disease.
- Preparation protocol: phenoxybenzamine 10 mg twice daily increasing over 7–14 days, liberal salt intake to expand volume, then propranolol or metoprolol; final targets — seated blood pressure near 130/85, mild orthostatic fall acceptable, no more than one or two minor spells per week; metyrosine for refractory cases.
- Never-first list: beta-blockers, diuretics before volume loading, and biopsies — no adrenal mass is biopsied before metanephrines are excluded.
- Genetics now standard: germline mutations in 30–40 per cent — RET (MEN2), VHL, NF1, SDHB/C/D; SDHB carriers have the highest metastatic risk; bilateral tumours in MEN2 and VHL justify cortex-sparing adrenalectomy to avoid lifelong adrenal insufficiency.
- Malignancy: defined by metastases, not histology — around 10–15 per cent of phaeochromocytomas; treatment combines alpha-blockade, 131I-MIBG therapy, temozolomide-based chemotherapy and tyrosine kinase inhibitors in selected patients.
- Intraoperative rule: phentolamine, magnesium and nicardipine stand ready for hypertensive surges on tumour handling; post-resection hypotension is treated with fluids and noradrenaline — the tumour's catecholamines have vanished but the receptors have not.
Preparing the patient for theatre
A 33-year-old woman with two months of pounding headaches, drenching sweats and recorded pressures to 210/120; plasma normetanephrine is six times the upper limit. Week one: phenoxybenzamine 10 mg twice daily begins — expect nasal congestion and postural giddling as alpha tone falls — with unlimited salt and at least 2.5 litres of fluid daily. Week two: dose up to 20 mg three times daily; her headaches thin out; propranolol 20 mg three times daily is added now, never before, to blunt the reflex tachycardia. Meanwhile CT shows a 4.5 cm right adrenal mass; because her age argues syndromic disease, calcium, PTH, calcitonin and RET testing are sent — a positive RET result would reframe this as MEN2, demand bilateral adrenal surveillance lifelong and push toward cortex-sparing surgery. Day before surgery: blood pressure 132/84 seated, 118/76 standing, mild postural symptoms accepted, haematocrit falling as volume returns — the classical sign of successful preparation. Laparoscopic adrenalectomy follows with invasive monitoring; she leaves on no antihypertensives. Follow-up: metanephrines at two to six weeks, then annually for at least ten years — recurrence and metachronous tumours are the reason surveillance never truly ends.
The classic confusion
The exam's favourite error is the beta-blocker-first patient who develops pulmonary oedema or crisis — unopposed alpha vasoconstriction; the sequence alpha → volume → beta is worth committing to muscle memory. The second confusion is hypertensive emergency pattern-matching: a young hypertensive with headaches is investigated for renal disease and thyroid disease while the metanephrines are never sent; the teaching rule — screen every paroxysmal, every young or resistant hypertensive, and every adrenal incidentaloma. The third is the adrenal-sparing question in hereditary bilateral disease: removing both glands converts one disease into another (adrenal insufficiency, with its crisis risk), so subtotal surgery is preferred where anatomy allows. Indian examiners add the "adrenal mass biopsy" stem — the answer is always the same: exclude phaeochromocytoma first.
Frequently asked questions
Which test makes the diagnosis of phaeochromocytoma?
Plasma free metanephrines (or 24-hour urinary fractionated metanephrines) drawn rested and off interfering drugs — plasma sensitivity exceeds 95 per cent, rising to near-certainty at levels several-fold above the reference limit.
Why must alpha-blockade precede beta-blockade?
Beta-blockade first leaves alpha-mediated vasoconstriction unopposed, precipitating hypertensive crisis — and in the volume-contracted patient can precipitate acute pulmonary oedema.
What defines adequate preoperative preparation?
Seven to fourteen days of phenoxybenzamine with salt loading, then beta-blockade, aiming for seated blood pressure around 130/85 with mild orthostatic fall, few spells and a falling haematocrit indicating volume re-expansion.
Which genetic tests are indicated in every new case?
Germline testing for RET, VHL, NF1 and SDHx mutations is now standard, since 30–40 per cent carry a heritable mutation — with cascade testing of first-degree relatives for identified mutations.
How long is follow-up after apparently curative surgery?
Lifelong annual biochemical surveillance is recommended — recurrence, metachronous tumours in hereditary disease and late metastases all appear years after apparent cure.