I think it is very useful to define a "gray area" as a hypertensive
reference interval in adult patients although different laboratories seem to
have quite different ideas of where the cut-offs should be for (a) normal
and (b) hypertensive normal, which is a worry. For example a cut off
for noradrenaline of 1000nmol/day seems very high.
I remember a case, long ago, of a patient with noradrenaline of around
600nmol/day and only very borderline raised VMA and metanephrins. I
recommended recollection and follow-up investigation but heard nothing
for over a year until the patient appeared at autopsy and we measured
tissue catecholamines from a highly encapsulated phaeochromocytoma.
This was a very unsatisfactory way of getting feedback on a ? false
negative result or failure to follow up borderline results.
Clearly the frequency of false negative cases (or risk of a false
negative) will be greater, the higher a laboratory sets their upper limits
and will be greater in the "hypertensive grey area" reference interval
than for the normal reference interval. I think Dr O'Connor's current
normal reference intervals are quite reasonable but only one 24 hour
collection is necessary. Laboratories which restrict ingestion of
bananas and tropical fruit (especially in areas where this is a significant
part of the diet) during collection will probably set a lower reference
interval and have somewhat greater sensitivity for phaeo detection than
those which don't. Where we set reference ranges might also depend
upon the kind of follow up the patient is likely to get. The ideal would
perhaps be as follows:
1. All results within normal reference interval
Phaeochromocytoma excluded (if not on MAOI, COMTI medication)
Hypertension (if present) is probably not catecholamine mediated.
2. Borderline raised noradrenaline or adrenaline.
(hypertensive reference interval)
Most likely cause is catecholamine mediated hypertension but phaeo is
still a possibility. Protocols for follow-up developed in conjunction with
clinicians. Different protocols used, perhaps depending upon degree of
elevation, pattern of raised metabolites and current medication. Examples
include: Repeat urine collection at a later date. Repeat on diet. Suspend
medication and repeat collection. Further clinical follow up. Clonidine
supression. Plasma catecholamines ? MIBG etc scans.
3. Highly elevated amines and metabolites. Phaeochromocytoma
indicated. Perform scans to confirm/locate tumour.
John Earl
Neurochemistry Laboratory
New Children's Hospital
Sydney, Australia
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