Specimen Collection
NOTE: Urine metanephrines is the preferred test for phaeochromocytoma; HVA, 3-methoxytyramine and catecholamines are the appropriate tests for neuroblastoma.
FOR URGENT REQUEST PLEASE CONTACT LABLINK ON 22000
ADULT
20mL 6mol/L HCl
.
Urine catecholamine requests in adults are not usually performed unless by special arrangement with a Chemical Pathologist. For requests on patients 16 years and older urine metanephrines will be performed instead. Please refer to the urine metanephrines test guide entry for sample requirements.
CHILDREN
Random samples from children are acceptable if there is difficulty collecting a 24 h specimen. In this case, concentrations will be related to creatinine output.
Casual paediatric specimens must be acidified within 2 hours of collection. Minimum sample 2 mL.
For casual collects on children at ACH the following protocol is used:
1. Once the sample is collected, send
immediately
to the laboratory. Please mark request form with a
"Paediatric catecholamine - Urgent"
sticker
so that samples
are treated with HCl as soon as possible.
2. HVA and metanephrine levels will also be measured automatically on all samples from children 15 years of age and under.
3. Ward staff are to ensure samples are handed to a laboratory staff member, and not just placed in the specimen reception tray.
Interferences
The most common drugs that cause interference are labetolol, L-dopa and sinemet. Other drugs such as some psychotropics, e.g. MAOI's, can also affect results.
Reference Intervals
24-hour urines
Reference interval:
|
Age
|
Adrenaline
(nmol/d)
|
Noradrenaline
(nmol/d)
|
10-19 years
|
< 110
|
< 470
|
19 years or older
|
< 100
|
< 760
|
|
Age
|
Dopamine
(umol/d)
|
10-15 years
|
< 2.9
|
15 years or older
|
< 4.0
|
|
Age
|
Adrenaline / Creatinine
(nmol/mmol)
|
Noradrenaline / Creatinine
(nmol/mmol)
|
Dopamine / Creatinine
(umol/mmol)
|
10-15 years
|
< 8
|
< 51
|
< 0.38
|
15 years or older
|
< 9.5
|
< 69
|
< 0.46
|
Uncertainty of Measurement:
Adrenaline 12%, Noradrenaline 10%. Dopamine 12%
Random urines
Reference intervals:
Age
|
Adrenaline / Creatinine
(nmol/mmol)
|
Noradrenaline / Creatinine
(nmol/mmol)
|
|
< 1 year
|
< 69
|
< 278
|
|
1-4 years
|
< 65
|
< 196
|
|
4-10 years
|
< 50
|
< 179
|
|
10-15 years
|
< 14
|
< 74
|
Age
|
Dopamine / Creatinine
(umol/mmol)
|
|
< 3 months
|
< 2.0
|
|
3 months - 1 year
|
< 1.7
|
|
1-2 years
|
< 1.3
|
|
2-5 years
|
< 0.9
|
|
5-10 years
|
< 0.7
|
|
10-15 years
|
< 0.4
|
Turnaround Time: Within 1 week
Performed Weekly.
Special arrangements can be made following discussions with Chemical Pathologist if urgent testing is required.
Urine HVA will be prioritised for urgent testing due to faster turnaround time.
Assay Method
Principle
: High performance liquid chromatography with electrochemical detection (HPLC-EC)
Contact Information
Emails to
chemicalpathologist@adhb.govt.nz
will receive priority attention from the on-call chemical pathologist.
If the query concerns a specific patient please include the NHI number in your email.
If email is not a suitable option, please contact the on-call chemical pathologist via
Lablink (Auckland City Hospital ext. 22000 or 09-3078995).
Individual chemical pathologists may be contacted but will not be available at all times.
After-hours
: contact
Lablink (Auckland City Hospital ext. 22000 or 09-3078995) or hospital operator for on duty staff after hours.
Dr Samarina Musaad
(Clinical Lead)
:
SamarinaM@adhb.govt.nz
ext. 22402
Dr Cam Kyle:
CampbellK@adhb.govt.nz
ext 22052
Dr Weldon Chiu:
WeldonC@adhb.govt.nz
ext. 23427
Dr Campbell Heron:
CHeron@adhb.govt.nz
ext. 23427
Confirming the Diagnosis of Phaeochromocytoma
The first-line tests are:
1.
Urine metanephrines
in a 24 hour urine collection (adults) or a spot urine (children).
2. Plasma metanephrines
(5mL EDTA blood).
Urine and plasma metanephrines have equal diagnostic accuracy (sensitivity and specificity) and are better than other tests (below)
Other tests
Urine catecholamines
may be helpful if urine and plasma metanephrines are borderline.
Plasma catecholamines
are difficult to measure and to interpret as they fluctuate widely depending on posture, anxiety etc. They are very rarely required, and only done as part of a clonidine suppression test.
Catecholamines, Medication and Diet
No special dietary precautions are necessary, because the HPLC method used at Labplus does not have any problems with food interferences.
The following drugs may cause false positive results:
Clozapine
has been reported to cause hypertension, with symptoms similar to phaeochromocytoma, and raised urine noradrenaline and normetadrenaline levels (up to 3 x normal) (ref: Krentz AJ. Psuedophaeochromocytoma syndrome associated with clozapine. Brit Med J, 2001;322:1213
Labetalol
interferes with the adrenaline peak seen during analysis, which may lead to a falsely increased adrenaline result.
L-dopa
will cause an increased dopamine
Tricyclic antidepressants
and
phenoxybenzamine
are likely to cause increases in noradrenaline and/or adrenaline. SSRIs do not have this effect.
Alpha-blockers
,
beta-blockers
,
calcium channel blockers
,
phenothiazines
and
theophylline
may cause small (up to 2x) increases in noradrenaline and/or adrenaline.
Please list all medications on the request form
. Some other medications produce peaks on the HPLC tracing but they can be distinguished from the catecholamines. If we see some unusual peaks, it is helpful if we can relate them to the patient's medication.
Dopamine and neuroblastoma
Dopamine and its metabolite HVA are increased in neuroblastoma. An isolated increase in urinary dopamine excretion is a fairly common non-specific finding in both children and adults, and is probably not clinically significant if there is no clinical suspicion of neuroblastoma. Most of the dopamine found in normal urine is produced by the kidneys rather than elsewhere in the body. Phaeochromocytomas which secrete only dopamine are very rare. Huge increases in urinary dopamine are seen in patients who are taking L-dopa.
Urine metanephrines are performed 2-3 times per week. Urine catecholamines are performed once a week (i.e. turnaround time of up to 2 weeks depending on arrival). As these are highly specialised analyses, we would like to avoid testing at night or weekends, so please aim to provide/send early specimens to us wherever possible.
LabPlus uses advanced technology (tandem mass spectrometry) to perform urine HVA tests; which results in significantly faster turnaround time.
If urgent testing is required, Urine HVA will be done.
Prior approval by a chemical pathologist is required for the laboratory to perform urgent testing.
Urine catecholamines are not offered as an urgent service. However, if asked the on-call chemical pathologist can consider this as an unusual request on a case by case basis, depending on clinical suspicion and the HVA result.
Urine metanephrines carry excellent diagnostic utility for neuroblastic tumours. Their use is being increasingly adopted by laboratories across Australasia. Urine metanephrines (including methoxytyramine), catecholamines and HVA are performed on every paediatric request to maximise sensitivity, regardless of whether the clinical indication is for neuroblastoma or phaeochromocytoma.
A review of local data consisting of 20 new neuroblastoma cases indicated that the sensitivity of urine HVA and methoxytyramine was approximately 90% while dopamine alone was 76%. No new cases of neuroblastoma had an isolated urine dopamine/creatinine ratio increase. The specificity of urine methoxytyramine, dopamine and HVA are approximately 90% for new cases.
If clinically indicated, variations to this agreement, such as plasma metanephrines/methoxytyramine, can be available by arrangement by contacting the on-call chemical pathologist.
24h versus spot urine
24h urine specimens are preferred over spot urines. A 24 hour urine specimen is more likely to detect brief peaks in catecholamine secretion than a random specimen.
24 hour urinary creatinine excretion is used as a guide to the completeness of a urine collection.
References:
-
Rosano TG.
Clin Chem
30(1984)301-3
-
LabPlus data
-
Eisenhofer et al. Biochemical diagnosis of phaeochromocytoma: how to distinguish true from false positive results.
J Clin Endo Metab
. 88:2656-66,2003.