Phaeochromocytoma is a tumour of the chromaffin cells located in the adrenal medulla. These are the cells that produce catecholamines - noradrenaline, adrenaline and dopamine. 15% of cases, however, arise from extra-adrenal chromaffin cells within the sympathetic ganglia (paravertebral). These are known as paragangliomas. They are mostly benign tumours.
They are rare, with <1 in 100,000 diagnosed annually. It is most commonly seen in ages 30-50 years old with no gender disparity.
Pathophysiology
Phaeochromocytomas are mostly sporadic, but in children they are more likely to be hereditary. They are associated with with the RET gene (in MEN2) and the VHL gene (in Von Hippel-Linadau syndrome), and the NF1 gene (in neurofibromatosis type 1). Familial tumours are associated with low levels of catecholamine release but the sporadic types are associated with higher catecholamine release.
These tumours secrete adrenaline and noradrenaline mostly and rarely dopamine. Phaeochromocytomas are characterised by predominantly raised adrenaline or both adrenaline and noradrenaline. Paragangliomas are characterised by raised noradrenaline without adrenaline being raised.
They are mostly benign but may also, less commonly, be malignant. However, they are both very similar in their biochemical presentation.
There is a 10% rule to describe the patterns of these tumours:
- 10% bilateral
- 10% cancerous
- 10% extra-adrenal
- 10% happen in children.
⚠️ Risk factors
- Multiple endocrine neoplasia 2 (MEN2) syndrome
- Von Hippel-Lindau syndrome
- Neurofibromatosis 1
- Familial paraganglioma syndrome
- Germline mutations - in the succinate dehydrogenase subunit B, C, and D genes.
😷 Presentation
Catecholamines are secreted in intermittent bursts, so patients fluctuate between symptomatic and asymptomatic. Symptoms increase their frequency and effect in proportion to the size of the tumour.
- Hypertension - this is the most common sign. The hypertension is sustained or paroxysmal. The paroxysms are unpredictable in their onset but may be induced by multiple factors such as exercise, foods, medications, IV contrast, surgery.
- Hypertensive retinopathy
- Headache - throbbing in nature
- Orthostatic hypotension - thought to be due to volume contraction secondary to alpha-adrenergic stimulation.
- Palpitations
- Diaphoresis
- Pallor - due to vasoconstriction that occurs with increased catecholamine release.
- Impaired glucose tolerance - increased levels of catecholamine increases glycogenolysis and inhibits insulin secretion.
- Polycythaemia - if EPO is secreted by tumour cells.
🔍 Investigations
- 🥇 24-hour urine collection for catecholamines, metanephrines, normetanephrines, and creatinine - these should all be elevated. They are preferably collected immediately after a crisis.
- 🥇 Plasma free metanephrines and normetanephrines - these should all be elevated. Plasma catecholamines may also be collected but they are more likely to give false negatives as they are released episodically, unlike plasma metanephrines which are released continuously.
- Genetic testing - patients should undergo genetic testing after being diagnosed. This is to identify if there is a hereditary cause that would necessitate further evaluation.
- Imaging - a CT scan is the modality of choice and is necessary to locate the tumour.
- If imaging does not identify a tumour but the blood and/or urine have derangements, we should do an iodine-labelled metaiodobenzylguanidine (MIBG) scan. MIBG has a similar structure to noradrenaline and it concentrates within phaeochromocytomas.
- U&Es - calcium may be elevated in MEN2 and potassium is reduced in the setting of high catecholamines.
🧰 Management
- 🏆 Surgery - adrenalectomy is the definitive management. It may be done laparoscopically (<6cm) or or open if larger.
Pateients should be given antihypertensives while waiting for surgery:
- 🥇 Alpha-blockers - such as phenoxybenzamine or doxazosin.
- 🥈 Beta-blockers - added onto the alpha-blockers if necessary.
⚠️ Do not treat with a beta-blocker alone as this will allow for unopposed alpha-mediated vasoconstriction.
🚨 Management of hypertensive crisis:
Antihypertensives should be given intravenously.
- Phentolamine
- Sodium nitroprusside
🚨 Complications
- Hypertensive crisis
- Hypertensive encephalopathy
- Stroke
- Left-ventricular failure
- Myocardial infarction