Torsades de Pointes: A Rare Complication of an Extra-Adrenal Pheochromocytoma

1263 Hypertens Res Vol.30 (2007) No.12 p.1263-1266 Case Report Torsades de Pointes: A Rare Complication of an Extra-Adrenal Pheochromocytoma Heiko METHE1), Martin HINTERSEER1), Ute WILBERT-LAMPEN1), Britt M. BECKMANN1), Gerhard STEINBECK1), and Stefan KÄÄB1) Pheochromocytoma is an infrequent secondary cause of arterial hypertension, often associated with paroxysmal headache, sweating, weight loss, and palpitations. Cardiovascular complications of pheochromocytoma include sudden death, heart failure due to toxic cardiomyopathy, and hypertensive encephalopathy. Here we report the case of a female with an acquired long-QT-syndrome as a rare complication of an extraadrenal pheochromocytoma. Diagnosis was made after sotalol-induced Torsades de Pointes. (Hypertens Res 2007; 30: 1263–1266) Key Words: pheochromocytoma, long-QT-syndrome, Torsades de Pointes Introduction Pheochromocytoma is a rare cause of sustained hypertension or hypertensive crisis and many cardiac complications have been reported with this neuroendocrine tumor. Development of long-QT-syndrome (LQTS) due to myocardial hypertrophy in this patient group is an occasional but potentially lifethreatening complication increasing the risk for arrhythmias. Case Report A 33-year-old female was referred to our hospital because of syncope. The patient had been well until 2 years earlier, when arterial hypertension was diagnosed and β-blocker treatment (bisoprolol 5 mg once daily) had been initiated by her primary care physician. She also reported loss of weight, paroxysmal sweating, emesis, and non-exertional tremor, yet no further diagnostic procedures were initiated. Because of palpitations, bisoprolol was switched to sotalol. The syncope occurred after a cumulative dose of 320 mg sotalol. On initial examination her blood pressure was 220/90 mmHg and her heart rate was 106 beats per minute. The remaining physical findings were normal, except for a 4/6 pansystolic murmur at Erb. There was no family history of sudden death. Serum electrolytes were as follows: sodium 139 mmol/L, potassium 5.1 mmol/L, calcium 2.7 mmol/L, anorganic phosphorus 4.1 mg/ dL, magnesium 1.97 mg/dL. Fasting blood glucose was elevated to 124 mg/dL. Renal, liver and thyroid tests were all normal. Her baseline ECG showed sinus rhythm and deep T-wave inversion in V2–4. Most remarkably it showed a QTc interval of 480 ms (Fig. 1A). Sotalol-treatment was discontinued immediately but during intensive care unit monitoring, a Torsades de Pointes tachycardia was recorded (Fig. 2), and was terminated by magnesium sulfate (1 g i.v.) infusion. Echocardiography showed hypertrophic cardiomyopathy with marked septal hypertrophy (interventricular septal diameter [IVSd] 21 mm, posterior wall diameter [PWd] 17 mm (physiologic: 6–12 mm; Fig. 3). There were no segmental wallmotion abnormalities and fractional shortening was 58%. Invasive diagnosis revealed patent coronary and renal arteries. Left ventriculography showed homogenous unaffected contractility with a small left ventricular cavity that occluded almost completely late systolic. No ventricular arrhythmia could be induced by programmed ventricular stimulation. Twenty-four–hour urine metanephrine excretion was 16.1 mg, vanillylmandelic acid 70.4 mg, adrenaline 25.9 μg, nor- From the 1)Department of Cardiology, Ludwig-Maximilians-University, Munich, Germany. Address for Reprints: Heiko Methe, M.D., Department of Cardiology, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany. E-mail: Received April 16, 2007; Accepted in revised form July 16, 2007. 1264 Hypertens Res Vol. 30, No. 12 (2007) A B Fig. 1. Electrocardiograms in our patient at baseline (A) revealed QTc prolongation and deep T-wave inversion in V2–4. Six months after tumor extirpation, the QTc interval was within the physiologic range and the electrocardiogram did not show further abnormalities (B). Fig. 2. Intensive care unit monitor tracing of a typical episode of non-sustained polymorphic ventricular tachycardia in our patient under sotalol treatment. adrenaline 5,038 μg, homovanillin acid 10.5 μg and dopamine 6,736 μg excretion in 1,400 mL with physiologic values for 5-hydroxyindole-3-acetic acid. Based on the overall findings we suspected pheochromocytoma with subsequent development of left ventricular hypertrophy as the underlying cause of an acquired LQTS. The patient was started on an α-adrenergic blocker (phenoxybenzamine) and later on, a β-adrenergic blocker therapy was slowly added. MRI-scan and radioiodinated metaiodobenzylguanidine (131I-MIBG) whole-body scintigraphy revealed a left-sided paravertebral retroperitoneal tumor (5.5 × 4 × 7 cm) and multiple enlarged lymph nodes in its cranial surrounding. No mutations in exons 10, 11, and 13 of the RET oncogen could be found. In order to evaluate the pathogenic mechanism of QT-prolongation in this patient, a provocative i.v. sotalol test (2 mg/ kg i.v. over 20 min) was performed to reveal an intrinsic myocardial predisposition to disproportional QT-prolongation and cardiac arrhythmias upon extrinsic triggers (1). With Fig. 3. Baseline echocardiography showed hypertrophic cardiomyopathy with marked septal hypertrophy. marked left ventricular hypertrophy but sustained cardiac function, serum potassium within reference limits and in the absence of any other QT-prolonging medication, the patient displayed a marked increase in QTc-interval upon challenge with dl-sotalol (from 461 ms at baseline to 512 ms), which is consistent with an abnormal repolarization reserve (Fig. 4A). Genetic analysis revealed no mutations in five of the major genes predisposing to LQTS (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2). These genes account for approximately 80% of all congenital LQTS (2). The tumor that had locally invaded the aorta, vena cava, and the left v. iliaca could not be curatively resected. Postoperative palliative irradiation therapy was initiated (total of 55.8 GY). Biopsy confirmed the diagnosis of an extra-adrenal pheochromocytoma with positive staining for synaptophysin and neuron-specific enolase. Urine catecholamine levels and blood pressure returned to normal within 7 days. A second provocative i.v. sotalol test 6 months after extirpation demarked a persistent disproportional increase in QTc-inter- Methe et al: Torsades de Pointes and Pheochromocytoma 1265 Fig. 4. Upon exposure to i.v. dl-sotalol (2 mg/kg), the patient presented with a marked increase in QTc-interval revealing an abnormal repolarization reserve. A: Before tumor extirpation (treated with phenoxybenzamine). B: Six months after tumor extirpation (without concomitant treatment). val upon challenge (from 464 ms to 522 ms; Fig. 4B), whereas echocardiography revealed a reduction in left ventricular hypertrophy, although some degree of hypertrophy was still present (IVSd 14 mm, PWd 13 mm). Echocardiography 20 months after surgery showed normalization of the left ventricular wall index with sustained eje (...truncated)