Clonidine Suppression Test (Four-hour)

Plasma, frozen

One tube (3 mL) each for baseline specimen, two-hour specimen, three-hour specimen, and four-hour specimen

One tube (2.2 mL) each for baseline specimen, two-hour specimen, three-hour specimen, and four-hour specimen

Chilled lavender-top (EDTA) tube

The patient should abstain from smoking. Walnuts, bananas, and interfering medications should be avoided for a week prior to specimen collection. An indwelling heparinized catheter is recommended, as venipuncture can cause an increase in the substances for which testing is being performed. The patient should remain recumbent during the entire collection procedure. Thirty minutes after the insertion of the indwelling catheter, blood is drawn for the baseline catecholamine determination. Clonidine hydrochloride (0.3 mg) is given orally, and repeat specimens for plasma catecholamines are collected two and three hours later.¹

Diagnose pheochromocytoma and those paragangliomas that may secrete epinephrine, norepinephrine, or both. Such tumors may cause paroxysmal or persistent hypertension. Investigation of hypertensive patients, especially younger individuals, particularly when hypertension is paroxysmal, suggesting pheochromocytoma.²

Plasma levels are useful if elevated, especially during or immediately following an episode of hypertension, but false-negatives occur when the specimen is drawn during an uneventful period. Normotensive pheochromocytoma has been reported.³ False-positive results are common. Epinephrine secretion increases in response to cold and hypoglycemia. Drugs that may affect plasma norepinephrine levels include α- and β-adrenergic blockers, vasodilators, clonidine, bromocriptine, theophylline, phenothiazine, tricyclic antidepressants, labetalol, calcium channel blockers, converting enzyme inhibitors, bromocriptine, chlorpromazine, haloperidol, and cocaine.

High-pressure liquid chromatography (HPLC) with electrochemical (EC) detection

Several medications have been shown to prevent clonidine suppression, thus rendering false-positive results. These include β-adrenergic blockers, tricyclic antidepressants, and thiazide diuretics. If possible, these drugs should be discontinued 48 hours before collection. The α-adrenergic blocking agents do not interfere with clonidine suppression.² Several definitions of a normal plasma catecholamine response to clonidine have been postulated:

• A minimum plasma norepinephrine level ≤500 pg/mL⁴

• ≥50% norepinephrine decline from baseline and a norepinephrine level ≤500 pg/mL⁵

• A minimum plasma total catecholamine (norepinephrine+epinephrine) concentration ≤500 pg/mL⁶

Sjoberg et al have concluded that minimal suppression occurs two to three hours after clonidine administration with the greatest diagnostic accuracy (92%) obtained when the normal response is defined as a level of total plasma catecholamine ≤500 pg/mL. Taylor et al⁷ have demonstrated an increase in false-positive results by using the 50% reduction criteria. This is especially true if the baseline results are within the established reference interval.