Overview
Phaeochromocytoma Crisis
Topic Overview
Summary
Phaeochromocytoma crisis is a life-threatening catecholamine surge from a catecholamine-secreting adrenal tumour. It presents with severe paroxysmal hypertension, the classic triad (headache, sweating, palpitations), and can cause stroke, MI, cardiac arrhythmias, and pulmonary oedema. Treatment requires alpha-blockade FIRST (phentolamine or phenoxybenzamine), THEN beta-blockade. Beta-blockers alone are contraindicated (precipitate unopposed alpha vasoconstriction). Definitive treatment is surgical resection after medical stabilisation.
Key Facts
- Catecholamine storm: Adrenaline and noradrenaline from tumour
- Classic triad: Headache + sweating + palpitations (episodic)
- Treatment priority: Alpha-blockade FIRST (phentolamine IV or phenoxybenzamine PO)
- Never beta-block first: Causes unopposed alpha → worsens hypertension
- Surgical cure: Laparoscopic adrenalectomy after adequate alpha-blockade
- 10% rule: 10% malignant, 10% bilateral, 10% extra-adrenal (paraganglioma)
Clinical Pearls
The "rule of 10s" is outdated — but reminds us: 10% extra-adrenal, 10% bilateral, 10% malignant, 10% familial
Always alpha-block BEFORE beta-block — beta-blockers alone cause dangerous vasoconstriction
"Spells" with sweating, pounding headache, and pallor (not flushing) = think phaeochromocytoma
Why This Matters Clinically
Undiagnosed phaeochromocytoma causes sudden death, stroke, and MI. Anaesthesia and surgery without alpha-blockade precipitate crisis. Every clinician managing hypertensive emergencies must consider phaeochromocytoma, especially if the pattern is paroxysmal.
Visual Summary
Visual assets to be added:
- Catecholamine biosynthesis pathway diagram
- CT showing adrenal phaeochromocytoma
- Alpha-before-beta treatment algorithm
- Hypertensive crisis differential flowchart
Epidemiology
Incidence
- 2-8 per million/year
- 0.1-0.6% of all hypertensive patients
- Often diagnosed on adrenal incidentaloma workup
Demographics
- Peak age: 40-50 years
- Equal sex distribution
- 30-40% familial (MEN2, VHL, SDH mutations)
Associated Syndromes
| Syndrome | Gene | Features |
|---|---|---|
| MEN2A/2B | RET | Medullary thyroid cancer, hyperparathyroidism |
| Von Hippel-Lindau | VHL | Haemangioblastomas, renal cell carcinoma |
| Neurofibromatosis type 1 | NF1 | Café-au-lait spots, neurofibromas |
| SDH mutations | SDHB/D | Paragangliomas |
Pathophysiology
Catecholamine Secretion
- Tumour arises from chromaffin cells of adrenal medulla
- Produces catecholamines: Adrenaline, noradrenaline, dopamine
- Secretion is episodic → paroxysmal symptoms
- Precipitated by: Stress, anaesthesia, drugs, tumour manipulation
Cardiovascular Effects
- Alpha-1 receptors: Vasoconstriction → hypertension
- Beta-1 receptors: Tachycardia, increased contractility
- Combined effect: Severe hypertension, arrhythmias, cardiac strain
Why Hypertensive Crises Occur
- Paroxysmal catecholamine release
- Tumour manipulation (surgery, palpation)
- Certain drugs (opioids, glucocorticoids, dopamine antagonists)
- Anaesthetic induction
Complications of Uncontrolled Catecholamine Storm
- Stroke (haemorrhagic or ischaemic)
- MI
- Arrhythmias
- Takotsubo cardiomyopathy
- Pulmonary oedema
- Multi-organ failure
Clinical Presentation
Classic Triad (Episodic)
| Feature | Notes |
|---|---|
| Headache | Severe, pounding |
| Sweating | Profuse, often generalised |
| Palpitations | Tachycardia, awareness of heartbeat |
Other Features
Precipitants of Crisis
Red Flags
| Finding | Significance |
|---|---|
| BP over 180/120 with symptoms | Catecholamine crisis |
| End-organ damage (stroke, APO) | Emergency treatment |
| Paroxysmal "spells" | Classic for phaeochromocytoma |
| Known adrenal mass | Investigate for phaeochromocytoma |
Severe hypertension (paroxysmal or sustained)
Common presentation.
Pallor (not flushing — vasoconstriction)
Common presentation.
Anxiety, tremor
Common presentation.
Nausea
Common presentation.
Weight loss
Common presentation.
Clinical Examination
Vital Signs
- Severe hypertension
- Tachycardia
- May have postural hypotension (hypovolaemia from vasoconstriction)
General Examination
- Pallor
- Profuse sweating
- Tremor
- Anxiety
Look for Syndromic Features
- Café-au-lait spots (NF1)
- Mucosal neuromas (MEN2B)
- Marfanoid habitus (MEN2B)
Signs of End-Organ Damage
- Retinopathy
- Neurological deficit (stroke)
- Pulmonary oedema
Investigations
Biochemical Diagnosis
| Test | Details |
|---|---|
| Plasma metanephrines | Most sensitive; first-line |
| 24h urine metanephrines and catecholamines | Alternative or confirmatory |
| Chromogranin A | Raised in phaeochromocytoma |
Imaging
| Modality | Role |
|---|---|
| CT adrenals | Localisation; typical lesion over 3cm, heterogeneous, high attenuation |
| MRI | Better for extra-adrenal; "light bulb" T2 signal |
| MIBG scan | Functional imaging for paragangliomas, metastases |
| PET | 68Ga-DOTATATE or 18F-FDG if metastatic |
Genetic Testing
- Recommended for all patients (30-40% hereditary)
- Test for RET, VHL, SDHB/D, NF1
Classification & Staging
By Location
| Type | Location |
|---|---|
| Phaeochromocytoma | Adrenal medulla |
| Paraganglioma | Extra-adrenal (sympathetic or parasympathetic ganglia) |
By Behaviour
- Benign (90%)
- Malignant (10%) — metastatic spread
"Rule of 10s" (Historical — Less Accurate Now)
- 10% malignant
- 10% bilateral
- 10% extra-adrenal
- 10% familial (now known to be 30-40%)
Management
Acute Crisis — Emergency Treatment
1. Alpha-Blockade FIRST:
| Drug | Dose | Notes |
|---|---|---|
| Phentolamine | 5-10 mg IV bolus, repeat as needed | Short-acting; for acute crisis |
| Phenoxybenzamine | 10-20 mg PO BD, titrate | Long-acting; for pre-operative preparation |
2. Beta-Blockade AFTER Adequate Alpha-Blockade:
| Drug | Dose | Notes |
|---|---|---|
| Propranolol | 20-40 mg TDS-QDS | Only after alpha-blockade established |
| Esmolol | IV infusion | Short-acting, titratable |
NEVER GIVE BETA-BLOCKER ALONE — Causes unopposed alpha vasoconstriction → worsens hypertension
3. Other Agents:
- Calcium channel blockers (nicardipine) — alternative or add-on
- Magnesium sulphate — stabilises membrane
- Sodium nitroprusside — for severe hypertension
Pre-Operative Preparation
- Phenoxybenzamine for 10-14 days (alpha-blockade)
- Add beta-blocker once alpha-blocked (control tachycardia)
- High-salt diet + fluids (reverse vasoconstriction-induced hypovolaemia)
- Targets: BP under 130/80 seated; HR under 100
Definitive Treatment — Surgery
- Laparoscopic adrenalectomy (preferred)
- Open surgery if large or malignant
- Intra-operative BP lability managed by experienced anaesthetist
Post-Operative
- Hypotension common (catecholamine withdrawal)
- IV fluids
- Monitor for hypoglycaemia (rebound insulin effect)
- Follow-up: Annual plasma/urine metanephrines for recurrence
Complications
Of Crisis
- Stroke (haemorrhagic or ischaemic)
- Myocardial infarction
- Arrhythmias (VT, VF)
- Takotsubo cardiomyopathy
- Pulmonary oedema
- Multi-organ failure
- Death
Of Surgery
- Intra-operative hypertensive crisis
- Post-operative hypotension
- Bleeding
- Recurrence (if malignant or incomplete resection)
Prognosis & Outcomes
Surgical Cure
- 90% of benign phaeochromocytomas cured by surgery
- Hypertension resolves in 70-80%
Malignant Disease
- 5-year survival: 40-50% if metastatic
- Limited treatment options (MIBG therapy, chemotherapy)
Follow-Up
- Lifelong surveillance for recurrence
- Annual biochemistry
Evidence & Guidelines
Key Guidelines
- Endocrine Society Clinical Practice Guideline on Phaeochromocytoma and Paraganglioma (2014)
- European Society of Endocrinology Guidelines
Key Evidence
- Alpha-before-beta blockade reduces intra-operative complications
- Genetic testing recommended for all cases
Patient & Family Information
What is a Phaeochromocytoma?
A phaeochromocytoma is a rare tumour in the adrenal gland (above the kidney) that releases hormones causing high blood pressure and other symptoms.
Symptoms
- Episodes of severe headache
- Sweating
- Fast heartbeat (palpitations)
- High blood pressure
Treatment
- Medication to control blood pressure before surgery
- Surgery to remove the tumour
Genetic Testing
- About 1 in 3 cases are hereditary
- Your family may benefit from genetic testing
After Surgery
- Most people are cured and blood pressure returns to normal
- You will need regular check-ups
Resources
References
Primary Guidelines
- Lenders JW, et al. Pheochromocytoma and paraganglioma: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2014;99(6):1915-1942. PMID: 24893135
Key Reviews
- Pacak K, et al. Pheochromocytoma: recommendations for clinical practice from the First International Symposium. Nat Clin Pract Endocrinol Metab. 2007;3(2):92-102. PMID: 17237836
- Neumann HPH, et al. Pheochromocytoma. N Engl J Med. 2019;381(6):552-565. PMID: 31390501