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Test ID: CATP Catecholamine Fractionation, Free, Plasma

Reporting Name

Catecholamine Fract, Free, P

Useful For

Diagnosis of pheochromocytoma and paraganglioma, as an auxiliary test to fractionated plasma and urine metanephrine measurements (plasma metanephrine is the preferred test for this diagnosis)

 

Diagnosis and follow-up of patients with neuroblastoma and related tumors, as an auxiliary test to urine vanillylmandelic acid and homovanillic acid measurements

 

Evaluation of patients with autonomic dysfunction or failure or autonomic neuropathy

Clinical Information

The catecholamines (dopamine, epinephrine, and norepinephrine) are derived from tyrosine via a series of enzymatic conversions. All 3 catecholamines are important neurotransmitters in the central nervous system and also play a crucial role in the autonomic regulation of many homeostatic functions, namely, vascular tone, intestinal and bronchial smooth muscle tone, cardiac rate and contractility, and glucose metabolism. Their actions are mediated via alpha and beta adrenergic receptors and dopamine receptors, all existing in several subforms. The 3 catecholamines overlap, but also differ in their receptor activation profile and consequent biological actions. The systemically circulating fraction of the catecholamines is derived almost exclusively from the adrenal medulla, with small contributions from sympathetic ganglia.

 

The catecholamines are normally present in the plasma in minute amounts, but levels can increase dramatically and rapidly in response to change in posture, environmental temperature, physical and emotional stress, hypovolemia, blood loss, hypotension, hypoglycemia, and exercise.

 

In patients with pheochromocytoma (a potentially curable tumor of catecholamine-producing cells of the adrenal medulla), or less commonly of sympathetic ganglia (paraganglioma), plasma catecholamine levels may be continuously or episodically elevated. This results in episodic or sustained hypertension and in intermittent attacks of palpitations, cardiac arrhythmias, headache, sweating, pallor, anxiety, tremor, and nausea. Intermittent or continuous elevations of the plasma levels of 1 or several of the catecholamines may also be observed in patients with neuroblastoma and related tumors (ganglioneuroblastomas and ganglioneuromas) and, very occasionally, in other neuroectodermal tumors.

 

At the other end of the spectrum, inherited and acquired syndromes of autonomic dysfunction or failure and autonomic neuropathies are characterized by either inadequate production of 1 or several of the catecholamines or by insufficient release of catecholamines upon appropriate physiological stimuli (eg, change in posture from supine to standing, cold exposure, exercise, stress).

Interpretation

Diagnosis of Pheochromocytoma:

This test should not be used as the first-line test for pheochromocytoma, as plasma catecholamine levels may not be continuously elevated, but only secreted during a "spell." By contrast, production of metanephrines (catecholamine metabolites) appears to be increased continuously. The recommended first-line laboratory tests for pheochromocytoma are:

-PMET / Metanephrines, Fractionated, Free, Plasma: the most sensitive assay

-METAF / Metanephrines, Fractionated, 24 Hour, Urine: highly specific and almost as sensitive as PMET

 

However, plasma catecholamine measurements can still be useful in patients whose plasma metanephrine or urine metanephrine measurements do not completely exclude the diagnosis. In such cases, plasma catecholamine specimens, if drawn during a "spell," have a 90% to 95% diagnostic sensitivity when cutoffs of >750 pg/mL for norepinephrine and >110 pg/mL for epinephrine are employed. A lower value during a "spell," particularly when plasma or urinary metanephrine measurements were also normal, essentially rules out pheochromocytoma. Unfortunately, the specificity of these high-sensitivity cutoff levels is not good for separating tumor patients from other patients with similar symptoms. When more specific (95%) decision levels of 2,000 pg/mL for norepinephrine or 200 pg/mL for epinephrine are used, the assay's sensitivity falls to about 85%.

 

Diagnosis of Neuroblastoma:

Vanillylmandelic acid, homovanillic acid, and sometimes urine catecholamine measurements on spot urine or 24-hour urine are the mainstay of biochemical diagnosis and follow-up of neuroblastoma. Plasma catecholamine levels can aid diagnosis in some cases, but diagnostic decision levels are not well established. The most useful finding is disproportional elevations in 1 of the 3 catecholamines, particularly dopamine, which may be observed in these tumors.

 

Diagnosis of Autonomic Dysfunction or Failure and Autonomic Neuropathy:

Depending on the underlying cause and pathology, autonomic dysfunction or failure and autonomic neuropathies are associated with subnormal resting norepinephrine levels, or an absent rise of catecholamine levels in response to physiological release stimuli (eg, change in posture from supine to standing, cold exposure, exercise, stress), or both. In addition, there may be significant abnormalities in the ratios of the plasma values of the catecholamines to each other (normal: norepinephrine>epinephrine>dopamine). This is observed most strikingly in the inherited dysautonomic disorder dopamine-beta-hydroxylase deficiency, which results in markedly elevated plasma dopamine levels and a virtually total absence of plasma epinephrine and norepinephrine.

Analytic Time

2 days

Day(s) and Time(s) Performed

Monday, Friday

Clinical Reference

1. Young WF Jr: Pheochromocytoma and primary aldosteronism. In Endocrine Neoplasms. Edited by A Arnold. Boston, Kluwer Academic Publishers, 1997, pp 239-261

2. Hernandez FC, Sanchez M, Alvarez A, et al: A five-year report on experience in the detection of pheochromocytoma. Ann Intern Med 2000;33:649-655

3. Pacak K, Linehan WM, Eisenhofer G, et al: Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma. Ann Intern Med 2001;134:315-329

4. Alexander F: Neuroblastoma. Urol Clin North Am 2000;27:383-392

5. McDougall AJ, McLeod JG: Autonomic neuropathy, I. Clinical features, investigation, pathophysiology, and treatment. J Neurol Sci 1996;137:79-88

6. Lenders JW, Pacak K, Walther MM, et al: Biochemical diagnosis of pheochromocytoma: which test is best? JAMA 2002;287:1427-1434

Method Name

High-Performance Liquid Chromatography (HPLC)

Includes unconjugated norepinephrine, epinephrine, and dopamine

Specimen Type

Plasma EDTA Meta


Advisory Information


Unless the purpose of the measurement is drug monitoring, discontinue any epinephrine, norepinephrine, or dopamine injections or infusions for at least 12 hours before specimen draw.

 

Do not perform the test on patients withdrawing from legal or illegal drugs known to cause rebound plasma catecholamine release during withdrawal (see Cautions for details)



Specimen Required


Patient Preparation: Discontinue drugs that release epinephrine, norepinephrine, or dopamine, or hinder their metabolism for at least 1 week before obtaining the specimen (see Cautions for details). If this is not possible for medical reasons, contact the laboratory and discuss whether a shorter drug withdrawal period may be possible in a particular case.

 

The patient must refrain from eating, using tobacco, and drinking caffeinated beverages for at least 4 hours before the specimen is drawn.

 

Supplies: Catecholamine tubes containing EDTA-sodium metabisulfite solution (T066) (tubes have a 6-month expiration time)

 

Submission Container/Tube: Plastic vial

Specimen Volume: 3 mL

Collection Instructions:

1. Drawing from a catheter is required.

2. Calm the patient by giving complete instructions and reassurance regarding the procedure.

3. Insert an indwelling intravenous catheter. Flush with 3 mL of NaCl, using positive pressure.

4. Have the patient rest for 30 minutes in the supine position in a quiet room.

5. At the end of the 30 minutes, withdraw and discard a minimum of 3 mL of blood to remove the saline out of the catheter.

6. If provocative sampling (eg, standing specimen) is required, perform provocative maneuver immediately after obtaining supine specimen. Obtain standing specimen immediately.

7. For each specimen, draw 10 mL of blood into the chilled EDTA-sodium metabisulfite 10-mL tube.

8. Specimens must remain at refrigerated temperature during processing and transport.

9. Separate plasma in a refrigerated centrifuge within 30 minutes of draw.

10. Freeze specimen immediately.


Specimen Minimum Volume

2 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Plasma EDTA Meta Frozen 7 days

Reference Values

NOREPINEPHRINE

Supine: 70-750 pg/mL

Standing: 200-1,700 pg/mL

 

EPINEPHRINE

Supine: ≤111 pg/mL

Standing: ≤141 pg/mL

 

DOPAMINE

<30 pg/mL (no postural change)

 

For SI unit Reference Values, see https://www.mayocliniclabs.com/order-tests/si-unit-conversion.html

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

82384

LOINC Code Information

Test ID Test Order Name Order LOINC Value
CATP Catecholamine Fract, Free, P 34551-2

 

Result ID Test Result Name Result LOINC Value
2846 Norepinephrine 2666-6
2901 Epinephrine 2230-1
2906 Dopamine 2216-0
Mayo Clinic Laboratories | Neurology Catalog Additional Information:

mml-Autonomic, mml-Pediatric