Phaeochromocytoma

DEFINITION

Rare, slow growing catecholamine-secreting tumours arising from chromaffin cells, which may be malignant.
The 10% tumour
10% extra-adrenal, 10% malignant, 10% bilateral, 10% hormonally inactive
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EPIDEMIOLOGY

Rare
<0.01% of general population

Up to 25% have a genetic association
- >10% can be bilateral and extra-adrenal.

Genetic Associations
Familial syndromes include:
- von Hippel-Lindau syndrome (VHL gene)
MEN2 (RET protooncogene)
NF1 (NF1 gene)
Familial paraganglioma / phaeochromocytoma syndrome (mitochrondrial succinate dehydrogenase gene)


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AETIOLOGY

Tumour of chromaffin cells
- 90% from adrenal medulla
- 10% from extra-adrenal chromaffin tissue
--> para-aortic sympathetic chain
--> organ of Zuckerkandl at origin of inferior mesenteric
--> sympathetic chain at neck or mediastinum
--> wall of urinary bladder


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BIOLOGICAL BEHAVIOUR

Pathophysiology
Secrete catecholamines

Delay to diagnosis can be associated with MI, cerebrovascular catastrophy.

Metastatasis
More common in extraadrenal sites
And in women.

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MANIFESTATIONS

Triad of headache, sweating and palpitations.
--> 'hypertensive spell'

High BP is variable
- spontaneous, or triggered,e.g. by anxiety, exercise, defecation, medications or postural changes
- speels associated with urination associated with bladder lesions.
- may be new, refractory, paroxysmal or recently worse

Also:
- anxiety
- chest / abdo pains
- visual blurring
- nausea and vomiting


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INVESTIGATIONS

Biochemical Testing
24-h urine
- catcholamines, metanephrines and vanillymandelic acid used for screening
But measurement of plasma free metanephrines may be best test to exclude phaeo.
Bottom line:
Urinary metanephrines and chromogrannin A = best
- but note patients currently have to pay for chromogrannin A themselves.
- and some centers prefer to do the plasma metanephrines as well.

Notes on accurate plasma testing
Fast prior to taking
- No caffeine or paracetamol for 5d prior to testing
Rest supine for 20m before blood drawn
Numerous foods (e.g. cheese, banana, soy sauce), drugs (pseudoephidrene, panadol), antidepressants and antiemetics also interfere.

Imaging
Once biochemically established, need localization of the tumour.

CT or MRI of chest, abdo
CT = highly sensitive, accessible and cost-effective.
- CT with adrenal protocol (non-con, 60s then 15m delayed) can detect 95% (from below neck to below aortic bifurcation).
- most phaeos have HU > 10; strong enhancement, washout much less than for benign adenomas (adenomas do rapid washout).
- appear irregular, and periphery often more intense than the central portion.
- occasionally contain haemorrhagic, cystic or necrotic areas, even when benign.

MRI use:
- patients with allergy to contrast, children, pregnant women, and patients in whom no more radiation is desirable.
Isointense to hyperintense relative to liver on T1-weighted MRI and  hyperintense on T2, typically heterogenous.

MIBG scan
- CT and MRI are very sensitive but not very specific
- nuclear scintigraphy using 123-I-metaiodobenzymguanidine is highly specific and provides info on tumour function.
- only used when adrenal mass not identified or in suspected metastatic disease.
- used with thyroid blockade by saturated potassium iodide tds for 5 days, starting day before injection.

PET
- localization possible with FDG and CT, relevant for metastatic disease assessment.

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MANAGEMENT

Pre-Op

Surgical resection is treatment of choice.
But drug treatment needed first to:
1. Normalize BP, HR and function
2. Restore depleted volume
3. Prevent cardiovascular collapse from catecholamine storm.

Adrenergic blockage
Necessary in all patients; no standard regimen
- phenoxybenzamine = nonselective alpha blocker 10mg orally b.d.
--> begin at time of diagnosis, increase to tds until effective blockage
--> this is evidenced by postural hypotension or nasal congestion.
This causes chronic vasoconstriction, and thus volume contraction
--> encourage liberal salt and fluid intake to balance volume expansion
Some patients then get a rebound tachycardia
--> treat with B-blockade (but only if alpha-blockade fully achieved, or can get paradoxical hypertensive crisis and LVH due to unopposed alpha-adrenergic stimulation).
Goal of Beta-blockade is resting HR 60-80,
- metoprolol
- in refractory hypertension, metyrosone.

Intra-Op Management
Even with effective preoperative adrenergic blockade, a hypertensive crisis or tachyarrhythmia can ensue.
Patients must have peripheral and central venous access sorted and an experienced anaesthetist.
- intravenous titrtable agents to control BP mixed and available.
- nicardipine for Ca-channel blocking, and nitrprisside for vasodilation for rapid control of hypertension.
Ligate the vein to control catecholamine release
--> can cause rebound hypotension, in which case adrenergic administration may be required.


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REFERENCES