For a phaeochromocytoma to be diagnosed there should be a high index of suspicion. Almost 75 years ago Dr J E Howard from the John Hopkins Hospital preached that a thorough history searching for his 3 Hs (hypertension, hyperglycaemia and hypermetabolism) would often lead to a clinical diagnosis. It must be remembered that there are a number of diseases that can mimic the signs and symptoms of a phaeochromocytoma, so tests must be highly sensitive to the disease. The aim is to establish the biochemical diagnosis and locate the tumour.
In the past the urinary concentrations of catecholamine metabolites, catecholamine-o-methyl transferase (COMT) and vanillyl mandelic acid (VMA) were used to screen for the diagnosis. However the poor sensitivity of these tests has lead to the use of urinary free catecholamines tests. Normally a 24 hour urinary collection is done although it is possible to use nocturnal collection, one hour samples or on the spot collection. In a normal person the 24 hour urinary free noradrenaline is <675 nmol/day and for adrenaline it is <275nmol/day.
Serum analysis is also used, but is not used as frequently due to technical difficulties. During a paroxysmal crisis this type of test is useful to detect the abnormally high levels of catecholamine. In hypertensive patients a normal catecholamine result suggests a cause other than a catecholamine-secreting tumour.
Suppression tests are also used when anxiety may cause the readings of catecholamines to be ambiguous. Using pentolinium (2.5mg i.v. at t=0 and then sample plasma catecholamines at 0 and 1 hour) can help distinguish between tumour-produced catecholamines and those produced due to stress as it does not suppress catecholamines from tumours. Clonidine (300µg orally at t=0, plasma catecholamines sampled at 0, 120 and 180 minutes) may also be used for these purposes.
Imaging is an important tool in detecting the tumour. CT scanning has a 93% sensitivity, although it can only detect tumours >1.0 cm in diameter and is unable to distinguish between phaeochromocytoma, adrenal adenomas and myelolipomas.
A CT Scan of a Phaeochromocytoma - click to enlarge
MRI can detect the tumours with almost 100% sensitivity, due to better tissue characterisation. If a CT/MRI scan shows no tumour, yet the biochemical tests suggest the presence of one, then a whole body scan must be done to locate the tumour. Alternatively Metaiodobenzylguanidine (123-I-MIBG) scanning may be performed. This compound binds to chromaffin and can help visualise the lesion in up to 75% of cases. When used pre-operatively, this method has a sensitivity of 85-90% and a specificity of over 95%.
An MIBG Scan of a Phaeochromocytoma - click to enlarge