Catecholamine Fractionation, Free, 24 Hour, Urine
An auxiliary test to fractionated plasma and urine metanephrine measurements in the diagnosis of pheochromocytoma and paraganglioma
An auxiliary test to urine vanillylmandelic acid and homovanillic acid determination in the diagnosis and follow-up of patients with neuroblastoma and related tumors
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 play crucial roles 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. They 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), urine catecholamine levels may be elevated. This results in episodic or sustained hypertension and often in intermittent attacks of palpitations, cardiac arrhythmias, headache, sweating, pallor, anxiety, tremor, and nausea ("spells"). Elevations of the urine levels of 1 or several of the catecholamines also may 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/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).
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
<1 year: <2.6 mcg/24 hours
1 year: <3.6 mcg/24 hours
2-3 years: <6.1 mcg/24 hours
4-9 years: 0.2-10.0 mcg/24 hours
10-15 years: 0.5-20.0 mcg/24 hours
> or =16 years: <21 mcg/24 hours
<1 year: <11 mcg/24 hours
1 year: 1-17 mcg/24 hours
2-3 years: 4-29 mcg/24 hours
4-6 years: 8-45 mcg/24 hours
7-9 years: 13-65 mcg/24 hours
> or =10 years: 15-80 mcg/24 hours
<1 year: <86 mcg/24 hours
1 year: 10-140 mcg/24 hours
2-3 years: 40-260 mcg/24 hours
> or =4 years: 65-400 mcg/24 hours
Diagnosis of Pheochromocytoma:
This test should not be used as the first-line test for pheochromocytoma. PMET / Metanephrines, Fractionated, Free, Plasma (the most sensitive assay) and/or METAF / Metanephrines, Fractionated, 24 Hour, Urine (almost as sensitive and highly specific) are the recommended first-line laboratory tests for pheochromocytoma.
However, urine catecholamine measurements can still be useful in patients whose plasma metanephrines or urine metanephrines measurements do not completely exclude the diagnosis. In such cases, urine catecholamine specimens have an 86% diagnostic sensitivity when cut-offs of >80 mg/24 hour for norepinephrine and >20 mg/24 hour for epinephrine are employed. Unfortunately, the specificity of these cut-off levels for separating tumor patients from other patients with similar symptoms is only 88%. When more specific (98%) decision levels of >170 mg/24 hours for norepinephrine or >35 mg/24 hours for epinephrine are used, the assay’s sensitivity falls to about 77%.
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; 1 or more of these tests may be elevated.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Many alterations in physiologic and pathologic states can profoundly affect catecholamine concentrations.
Any environmental factors that may increase endogenous catecholamine production should be avoided. These include noise, stress, discomfort, body position, and the consumption of food, caffeinated beverages, and nicotine. Caffeine and nicotine effects are short term, a few minutes to hours only.
Other substances and drugs that may affect the results include:
Substances that result in increased release or diminished metabolism of endogenous catecholamines:
-Monamine oxidase inhibitors (MOIs): a class of anti-depressants with marked effects on catecholamine levels, particularly if the patient consumes tyrosine rich foods, such as nuts, bananas, or cheese
-Catecholamine reuptake inhibitors including cocaine and synthetic cocaine derivatives, such as many local anesthetics, which also can be antiarrhythmic drugs (eg, lidocaine)
-Some anesthetic gases, particularly halothane
-Withdrawal from sedative drugs, medical or recreational, in particular alcohol, benzodiazepines (eg, Valium), opioids, and some central acting antihypertensive drugs, particularly Clonidine, but, generally not cannabis or other hallucinogens such as lysergic acid diethylamide (LSD), mescal, or peyote
-Vasodilating drugs (eg, calcium antagonists, alpha-blockers)
-Tricyclic antidepressants usually exert a negligible effect
Substances that reduce or increase plasma volume acutely (eg, diuretics, radiographic contrast media, synthetic antidiuretic hormone [eg, desmopressin 1-deamino-8-d-arginine vasopressin: DDAVP])
Historically, a third category of potentially interfering substances was represented by molecules that are either similar in chemical structure, antibody epitopes, or chromatographic migration pattern to the catecholamines, or have metabolites that can be mistaken for the catecholamines. Our current HPLC-based assay is not subject to any significant direct interference of this kind. In most cases, the following drugs do not cause problems with the current assay that cannot be resolved: acetaminophen, allopurinol, amphetamines and its derivatives (methamphetamine, methylphenidate [Ritalin], fenfluramine, methylenedioxymethamphetamine [MDMA: ecstasy]), atropine, beta blockers (atenolol, labetalol, metoprolol, sotalol), buspirone, butalbital, carbamazepine, clorazepate, chlordiazepoxide, chlorpromazine, chlorothiazide, chlorthalidone, clonidine, codeine, diazepam, digoxin, dimethindene, diphenhydramine, diphenoxylate, dobutamine, doxycycline, ephedrine and pseudoephedrine, fludrocortisone, flurazepam, guanethidine, hydralazine, hydrochlorothiazide, hydroflumethiazide, indomethacin, insulin, isoprenaline, isosorbide dinitrate, L-Dopa, methenamine mandelate (mandelic acid), methyldopa, methylprednisolone, nitrofurantoin, nitroglycerine, oxazepam, entazocine, phenacetin, phenformin, phenobarbital, phenytoin, prednisone, probenecid, progesterone, propoxyphene, propranolol, quinidine, spironolactone, tetracycline, thyroxine, and tripelennamine.
On occasion, when interference cannot be resolved, an interference comment will be reported.
The variability associated with age, gender, and renal failure is uncertain.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
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