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LETTER

Serotonin Reuptake Inhibitor Unmasks a Pheochromocytoma

Marc A.J. Seelen, MD; Paul H.E.M. de Meijer, MD, PhD; and A. Edo Meinders, MD, PhD

15 February 1997 | Volume 126 Issue 4 | Page 333

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To the Editor: We describe a 55-year-old man with attacks of headache, nausea, palpitations, and perspiration after the dose of paroxetine (a serotonin reuptake inhibitor prescribed for depression) was doubled to 40 mg/d. His other medications were atenolol and a benzodiazepine. Physical examination showed that the patient was agitated and had striking peripheral vasoconstriction. Blood pressure varied between 240/130 and 80/40 mm Hg; the patient did not have orthostatic hypotension. Because of the patient's paroxysmal symptoms and striking changes in blood pressure, a pheochromocytoma was suspected. A 24-hour urinalysis showed noradrenalin, 9.2 nmol (normal, 0.06 to 0.47 nmol); adrenalin, 27 nmol (normal, <0.16 nmol); and vannillylmandelic acid, 147 mmol (normal, <30 mmol). A tentative diagnosis of pheochromocytoma was made. Computed tomography of the abdomen showed a mass of approximately 4 cm in diameter in the left adrenal gland. Results of pathologic examination after left-sided adrenalectomy were compatible with pheochromocytoma. After surgery, the patient had no symptoms and was normotensive.

Increased concentrations of noradrenalin caused by inhibited presynaptic reuptake by tricyclic antidepressant drugs is a desirable effect, but it can induce hemodynamic abnormalities, especially when used with monoamine oxidase inhibitors or in patients with pheochromocytoma [1]. Selective serotonin reuptake inhibitors showed similar hemodynamic complications when used in combination with a monoamine oxidase inhibitor [2].

A difference in selectivity is known to exist between serotonin reuptake inhibitors; the dose-dependent inhibition of noradrenalin reuptake for paroxetine is 10% to 26%, as shown by animal studies. No such inhibition in therapeutic dosage has been established in humans [3].

The rate of paroxetine metabolism depends on the activity of an isozyme of cytochrome p450 (CYP2D6), which could differ between patients, with poor and extensive metabolizers [4]. Partial aspecific noradrenalin reuptake inhibition by serotonin reuptake inhibitors used in high doses, combined with an increased release of catecholamines from the pheochromocytoma, may have contributed to the hemodynamic abnormalities seen in our patient. An alternate explanation could be the higher sensitivity of the noradrenalin receptor in the presence of increased serotonin concentration in plasma by inhibition of serotonin reuptake by platelets [5].

This is the first report of the adverse effect of serotonin reuptake inhibitors in a patient with pheochromocytoma. Hypertension found during therapy with these agents should prompt clinicians to suspect drug interactions or an underlying pheochromocytoma.

Author and Article Information

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University Hospital Leiden, 2300 RC Leiden, the Netherlands

References

Top Author & Article Info References

1. Kaufmann JS. Phaeochromocytoma and tricyclic antidepressants [Letter]. JAMA. 1974;229:1282.

2. Montastruc JL, Chamontin B, Senard JM, Tran MA, Rascol O, Llau ME, et al. Pseudo phaeochromocytoma in a parkinsonian patient treated with fluoxetine plus selegiline [Letter]. Lancet. 1993;341:555.

3. Magnussen I, Tonder K, Engbaek F. Paroxetine, a potent selective long-acting inhibitor of synaptosomal 5-HT reuptakein mice. J Neural Trans. 1982;55:217-26.

4. Sindrup SH, Brosen K, Gram LF, Hallas J, Skjelboe E, Allen A, et al. The relationship between paroxetine and sparteine oxydation polymorphism. Clin Pharmacol Ther. 1992;51:278-87.[Medline]

5. Prichard BN, Smith CC. Serotonin: receptor and antagonist. Summary of symposium. Clin Physiol Biochem. 1990;8(Suppl 13):120-8.

This article has been cited by other articles:

				M. Prokhorova and S. Fritz Case of a 73-Year-Old Man With Dementia and a Likely Pheochromocytoma Mistaken for an Anxiety Disorder Psychosomatics, February 1, 2002; 43(1): 82 - 82. [Full Text]

				A S Kashyap Phaeochromocytoma unearthed by fluoxetine Postgrad. Med. J., May 1, 2000; 76(895): 303 - 304. [Abstract] [Full Text]

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