phaeochromocytoma

Question 1

def phaeo

Answer 1

catecholamine producing tumour

usually from sympathetic paraganglia cells (phaeochrome bodies) which are collections of chromaffin cells of adrenal medulla. Extra-adrenal in 10% cases

10% bilateral, 10% are malignant, 10% extra-adrenal, 10% familial

extra-adrenal phaeochromocytomas are referred to as paragangliomas - found by aortic bifurcation

Question 2

aetiology phaeo

Answer 2

mutations in the genes encoding subunits of the mitochondrial enzyme succinate dehydrogenase: SDHB, SDHD, SDHC. therefore FH important and referral for genetic screening (<50yrs)

90% are sporadic

10% are part of hereditory cancer syndromes eg thyroid, MEN-2A (multiple endocrine neoplasia type 2a), MEN-2B, neurofibromatosis type 1, von Hippel-Lindau syndrome (succinyl dehydrogenase mutations)

Mutations in VHL, SDHB and SDHD may contribute to the pathogenesis of tumours via dysregulation of the HIF-1 (hypoxia-inducible factor 1) and HIF-2 transcription factors.

Question 3

epi phaeo

Answer 3

rare

<0.2% of hypertensive patients

Question 4

triad phaeo

Answer 4

episodic headache

sweating

tachycardia

Question 5

sx phaeo

Answer 5

suspect if BP hard to control, accelarating or episodic

heart: palpitations, faints, chest pain, dyspnoea

CNS: headache, visual disorder, dizziness, tremor

psychological: anxiety, panic, confusion, hyperactivity, episodic psychosis, tremor, weakness
gut: D&V, abdo pain over tumour site, constipation

heat intolerance

backache

pallor

haemoptysis

symptoms may be precipiated by straining, exercise, stress, abdo pressure, surgery, B blockers, IV contrast agents or tricyclics

site of tumour may determine precipitants - pelvic - sex, parturition, defaecatuion, micturition

adrenergic crisis may last minutes to days

suddenly pt feels like going to die, the get better, then get stroke or cardiogenic shock

Question 6

signs phaeo

Answer 6

hypertension (50-70%) - 2/3 sustained, 1/3 paroxysmal

postural hypotension = secondary to reduced plasma vol

pallor

tachycardia

fever

weight loss

angina

MI/LVF, cardiomyopathy +- paradoxical shock

numbness

encephalopathy

horner’s syndrome (paraganglioma)

subarachnoid/CNS haemorrhage

abdo mass

mesenteric vasoconstriction

raised temp

episodic thyroid swelling

glycosuria during attacks

terminal haematuria from bladder phaeo

Question 7

ix phaeo

Answer 7

24hr urine collection in acid containing bottle

plasma free metanephrines in pts high risk (sensitivity 99%)

tumour localisation - CT or MRI scan

I-MIBG scintigraphy

screen for associated conditions

• MEN-2a: serum Ca and calcitonin
• VHL : ophthalmoscopy, MRI posterior fossa and renal USS
• NF 1: clinical exam for neurofibromas, cafe au lait spots and axillary freckling
• genetic testing and counselling: for mutations in VHL, SDHB, SDHD and RET genes in pts <20yrs, FH, bilateral tumours or familial disorder

Question 8

24hr urine collection in acid containing bottle phaeo

Answer 8

measurement of catecholamines (adrenaline, noradrenaline, dopamine) and fractioned metanephrines

• certain drugs may increase measured catecholamines eg TCA, levodopa

urinary creatinine should be measured to verify adequate collection

blood glucose

Ca may be raised

K may be low

raised WCC

Question 9

I-MIBG scintigraphy phaeo

Answer 9

chromaffin seeking isotope - find extra-adrenal tumours

for large (>10cm) phaeochromocytomas (increased risk of malignancy) or paraganglioma (increased risk of multiple tumours and malignancy) or if CT/MRI is negative but diagnosis considered likely due to clinical and biochemical evidence