22413 Catecholamine, Fractionation, Free, Plasma (CATP)

Catecholamines in plasma are chemically labile and the specimens must be handled carefully, both because of rapid specific metabolism and rapid oxidation on exposure to air. For example, plasma-free norepinephrine has a half-life of approximately 2 minutes. To enhance accuracy, one must pay careful attention to the circumstances of specimen collection and to the preparation of the patient (see Specimen Required).

Many alterations in physiologic and pathologic states can profoundly affect catecholamine concentrations.

Any environmental factor that may increase endogenous catecholamine production should be avoided. These include noise, stress, discomfort, body position, and the consumption of food, caffeinated beverages, or nicotine. Caffeine and nicotine effects are short term, a few minutes to hours only.

Other substances and drugs that may also affect the results include:
1. Substances that result in increased release or diminished metabolism of endogenous catecholamines
-Monoamine oxidase inhibitors (MOIs): a class of antidepressants 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, some of which are also antiarrhythmic drugs (eg, lidocaine)
-Some anesthetic gases, particularly halothane
-Withdrawal from sedative drugs, medical or recreational, particularly 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
2. 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])
3. Drugs that are metabolized to endogenous catecholamines. In the main, this concerns carbidopa and L-dopa. These drugs are converted to dopamine, and dopamine measurements for patients taking these drugs will be artifactually elevated. Since isolated dopamine elevations are extremely rare, they should always be viewed with suspicion. A review of the liquid chromatography tandem mass spectrometry (LC-MS/MS) trace should be requested. On a careful review, this methodology usually, but not always, allows identification of the unmetabolized parent drug, alongside dopamine.

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. The current LC-MS/MS-based assay is not subject to any significant direct interference of this kind. In particular, the following drugs, which used to be considered potential interferences, do not cause problems that cannot be resolved, in most cases, with the current assay: acetaminophen, allopurinol, amphetamines and its derivatives (methamphetamine, methylphenidate [Ritalin], fenfluramine, methylenedioxymethamphetamine [MDMA: ecstasy]), atropine, beta-blockers (atenolol, labetolol, metoprolol, sotalol), buspirone, butalbital, carbamazepine, chlorazepate, 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, pentazocine, phenacetin, phenformin, phenobarbital, phenytoin, prednisone, probenecid, progesterone, propoxyphene, propranolol, quinidine, spironolactone, tetracycline, thyroxine, and tripelennamine.

On occasions when interference cannot be resolved, an interference comment will be reported.

The variability associated with age, sex, and kidney failure is uncertain.​

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).