Clonidine Suppression

Rationale: This test has been used to diagnose pheochromocytoma and those paragangliomas that may secrete epinephrine, norepinephrine, or both. Such tumors may cause paroxysmal or persistent hypertension. The test is useful in the investigation of hypertensive patients, especially younger individuals, particularly when hypertension is paroxysmal, suggesting pheochromocytoma.1 Several definitions of a normal plasma catecholamine response to clonidine have been postulated:

  1. A minimum plasma norepinephrine level ≤500 pg/mL2
  2. ≥50% norepinephrine decline from baseline, and a norepinephrine level ≤500 pg/mL3
  3. A minimum plasma total catecholamine (norepinephrine + epinephrine) concentration ≤500 pg/mL4

Sjoberg et al5 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 al6 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. Plasma levels are useful if elevated, especially during or immediately following an episode of hypertension, but false-negative results occur when the specimen is drawn during an uneventful period. Normotensive pheochromocytoma has been reported.7 False-positive results are common. Epinephrine secretion increases in response to cold and hypoglycemia.

Protocol: The patient should fast overnight and abstain from smoking. 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.5 Collection of a fourth tube at four hours is optional.

Note: 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. Drugs that may affect plasma norepinephrine levels include α-adrenergic and β-adrenergic blockers, vasodilators, clonidine, bromocriptine, theophylline, phenothiazine, tricyclic antidepressants, labetalol, calcium channel blockers, converting enzyme inhibitors, bromocriptine, chlorpromazine, haloperidol, and cocaine.

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.

Orderable Tests: Clonidine Suppression Test (Three-hour) (123133) , Clonidine Suppression Test (Four-hour) (123158)

Note: For each collection time interval, draw blood into lavender-top (EDTA) tubes. Invert tubes to allow preservatives to mix thoroughly. Centrifuge and transfer the plasma to labeled plastic transport tubes (4 mL each; 2 mL minimum). Freeze immediately and ship frozen. The time between blood collection and the preparation of plasma is critical; if the time exceeds one hour, catecholamine values increase (when blood is refrigerated) or decrease (when kept at room temperature).8

References

1. Sheps SG, Jiang NS, Klee GG, van Heerden JA. Recent developments in the diagnosis and treatment of pheochromocytoma. Mayo Clin Proc. 1990 Jan; 65(1):88-95. PubMed 1967325

2. Bravo EL, Tarazi RC, Fouad FM, Vidt DG, Gifford RW Jr. Clonidine-suppression test: A useful aid in the diagnosis of pheochromocytoma. N Engl J Med. 1981 Sep 10; 305(11):623-626. PubMed 7266587

3. Manger WM, Gifford RW Jr, Hoffman BB. Pheochromocytoma: A clinical and experimental overview. Curr Probl Cancer. 1985 May; 9(5):1-89. PubMed 3021396

4. Bravo EL, Gifford RW Jr. Current concepts. Pheochromocytoma: diagnosis, localization, and management. N Engl J Med. 1984 Nov 15; 311(20):1298-1303. PubMed 6149463

5. Sjoberg RJ, Simcic KJ, Kidd GS. The clonidine suppression test for pheochromocytoma. A review of Its utility and pitfalls. Arch Intern Med. 1992 Jun; 152(6):1193-1197. PubMed 1599347

6. Taylor HC, Mayes D, Anton AH. Clonidine suppression test for pheochromocytoma: Examples of misleading results. J Clin Endocrinol Metab. 1986 Jul; 63(1):238-242. PubMed 3711261

7. Feldman JM, Blalock JA, Zern RT, et al. Deficiency of dopamine-beta-hydroxylase. A new mechanism for normotensive pheochromocytomas. Am J Clin Pathol. 1979 Aug; 72(2):175-185. PubMed 474494

8. Boomsma F, Alberts G, van Eijk L, Man in 't Veld AJ, Schalekamp MA. Optimal collection and storage conditions for catecholamine measurements in human plasma and urine. Clin Chem. 1993 Dec; 39(12):2503-2508. PubMed 8252722

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