Possible New Causes for False-Positive Diagnosis of Pheochromocytoma: Lamotrigine, Aripiprazole, or the Combination

Sir: Pheochromocytomas are rare neuroendocrine tumors diagnosed by elevated plasma and/or urine catecholamines or their metabolites.^1,2 Medications reported to cause false-positive serum or urine studies include acetaminophen, phenoxybenzamine, amitriptyline, labetolol, haloperidol, levodopa, tamsulosin, venlafaxine, hydrochlorothiazide, and buspirone.^2,3 We report a case in which lamotrigine, aripiprazole, or both caused symptoms and biochemical evidence suggesting pheochromo-cytoma that resolved when the drugs were discontinued. There are no previous reports of lamotrigine or aripiprazole associated with false-positive biochemical testing for pheochromocytoma.

Case report. Mr. A, a 60-year-old white man, presented in May 2005 with anxiety, palpitations, and panic attacks starting 3 months prior to evaluation, immediately after he underwent cardiac bypass surgery. He had no medical complications peri-operatively and initially attributed his symptoms to the stress of surgery. He was seen by Psychiatry and diagnosed with depression, attention-deficit/hyperactivity disorder, and bipolar disorder and placed on treatment with aripiprazole, lamotrigine, and venlafaxine.

Mr. A's attacks became more frequent, and he felt incapacitated. On examination, he appeared anxious. His blood pressure was 141/96 mm Hg, and his pulse was 97 bpm. The remainder of his examination was unremarkable. Additional medical history of the patient included hypothyroidism, hypertension, and obstructive sleep apnea. At initial presentation to the Division of Diabetes, Endocrinology and Metabolism, 3 months after his first evaluation by Psychiatry, his medications were lamotrigine, venlafaxine, and aripiprazole in addition to tamsulosin, aspirin, levothyroxine, amlodipine, benazepril, and rosuvastatin. He was taken off tamsulosin and venlafaxine to undergo biochemical testing for pheochromocytoma. Laboratory tests showed elevated urine and plasma normetanephrines (Table 1). Abdominal computed tomography scan and metaiodobenzyl-guanidine (MIBG) scan findings were normal.

Table 1.

Biochemical Workup for Pheochromocytoma

We discontinued lamotrigine and aripiprazole treatment and repeated plasma and urine studies 3 weeks later, at which time results of Mr. A's plasma and urine studies had normalized, and his symptoms had resolved (Table 1).

Lamotrigine is an antiseizure medication, and aripiprazole is a new atypical antipsychotic; both are used in the treatment of bipolar disorder. Lamotrigine prolongs the refractory phase of voltage-gated sodium channels.⁴ Aripiprazole is a partial D₂ agonist and acts differently from the existing atypical antipsy-chotics.⁵ Neither drug has an obvious mechanism for raising catecholamines or its metabolites. Given the severity of our patient's symptoms, both drugs were stopped simultaneously. His laboratory values returned to normal, and his symptoms resolved completely. He is unwilling to reintroduce each medication separately to determine if the effect observed was an individual drug effect or a synergistic occurrence. Additional reports are needed to evaluate this further. Given this case, we recommend considering lamotrigine and aripiprazole as 2 additional medications that could cause a false-positive biochemical result when evaluating for pheochromocytoma.

Dr. Goldner has received honoraria from Abbott and Takeda and has been a member of the speakers/advisory board for Takeda.