Phaeochromocytoma
Pheochromocytoma and Paraganglioma: An Endocrine Society Clinical Practice Guideline. Published: Jun 2014.
Definition
Phaeochromocytoma is a rare neuroendocrine tumour arising from the chromaffin cells of the adrenal medulla that secretes catecholamines (adrenaline, noradrenaline).
Aetiology
Phaeochromocytoma has a strong genetic basis (~40% of cases), key relevant hereditary syndromes include: [Ref]
- Multiple endocrine neoplasia type 2 (RET gene mutation)
- Von Hippel-Landau disease
- Neurofibromatosis type 1
~60% of cases are sporadic
- No definitive environmental risk factors have been established for sporadic phaeochromocytoma [Ref]
Clinical Features
Classic triad of episodic (uncommon for all 3 to be present): [Ref]
- Headache
- Palpitations
- Diaphoresis (profuse sweating)
Other features include: [Ref]
- Pallor
- Tremor and anxiety
- Nausea
Pheochromocytoma is often called “the great mimic” because symptoms can resemble numerous other conditions, including panic attacks, anxiety disorders, and various cardiovascular diseases.
Investigation and Diagnosis
To diagnose phaeochromocytoma, both of the following must be present:
- Biochemical evidence of catecholamine excess, and
- Imaging evidence of the tumour
Step 1: Biochemical Testing
Choice of test:
- Plasma-free metanephrines, or
- 24-hour urine free metanephrines
Interpretation:
- Elevated metanephrine levels (>2x upper limit) are strongly suggestive of phaeochromocytoma
To minimise false +ve, the patient should be in a supine position for at least 30 min before the blood is drawn.
Some causes of false +ve (mildly elevated metanephrine levels in patients without phaeochromocytoma): [Ref]
- Certain medications (e.g. TCA, antipsychotics, SSRI, SNRI, levodopa)
- Physiological stress (e.g. concurrent acute illness)
Step 2: Imaging Studies
Imaging studies should only be performed once there is clear biochemical evidence of phaeochromocytoma.
Choice of imaging:
- 1st line: CT abdomen and pelvis
- Other
- MRI – for those who cannot undergo CT (e.g. allergic to contrast, pregnant women, children)
- Functional imaging (e.g. PET/CT, MIBG scintigraphy) – used in metastatic disease
Other Testing
Genetic testing should be considered in all patients diagnosed with phaeochromocytoma.
Management
The definitive treatment is surgical removal of the tumour.
Extensive preoperative medical preparation is necessary to prevent life-threatening cardiovascular complications during the surgery. Phaeochromocytoma can massively release catecholamines during surgery (e.g. tumour manipulation, anaesthesia), which can cause hypertensive crisis, arrhythmias, and haemodynamic instability.
Pre-Operative Phase (MOST IMPORTANT)
Pre-operative medical management:
| Phase 1 – initial therapy | Give an alpha blocker for 7-14 days to normalise BP and heart rate |
|
| Phase 2 – once alpha blockage has been established | If heart rate remains >70 bpm → give a beta blocker to control heart rate |
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The “Alpha-First” Rule: A beta-blocker must never be started before adequate alpha-blockade has been established. Doing os causes a life-threatening hypertensive crisis due to “unopposed” alpha receptor stimulation by catecholamines.
DO NOT use labetalol as initial therapy. It is a mixed alpha and beta blocker, with predominantly beta blockade. If used initially, it can still result in relative “unopposed” alpha receptor stimulation.
Intra-Operative Phase
Primary choice: laparoscopic adrenalectomy
Other:
- Open resection is usually for large tumours / invasive tumours
- Partial adrenalectomy is suggested for those with bilateral tumour / hereditary disease to spare the adrenal cortex and prevent lifelong steroid dependence
Post-Operative Phase
Close monitoring of BP, heart rate, and blood glucose levels (patient is at particular risk of post-operative hypoglycaemia) is required for 24–48 hours
Plasma or urinary metanephrines should be measured 2-4 weeks after surgery to confirm successful removal of the tumour
Long-Term Follow-Up
Annual lifelong biochemical testing is necessary for ALL patients – due to the risk of recurrence and metastasis