Bradydysrhythmia-related presyncope secondary to pheochromocytoma

Journal of Internal Medicine 1997; 242: 249–253

C A SE R EP ORT

Bradydysrhythmia-related presyncope secondary to pheochromocytoma R. ZWEIKER a , M. TIEMANN a , B. EBER a , M. SCHUMACHER a , F.M. FRUHWALD a , R. LIPP a , S. LAX b , H. PRISTAUTZ c & W. KLEIN a From the Departments of aInternal Medicine and bPathology, Karl-Franzens-University of Graz and cHospital of Wagna, Austria

Abstract. Zweiker R, Tiemann M, Eber B, Schumacher M, Fruhwald FM, Lipp R, Lax S, Pristautz H, Klein W (University of Graz and Hospital of Wagna, Austria). Bradydysrhythmia-related presyncope secondary to pheochromocytoma (Case report). J Intern Med 1997; 242: 249–53. Pheochromocytoma endures as a life-threatening disorder. In the absence of systemic hypertension, diagnosis may be difficult. We present a 46-year-old normotensive male with a history of presyncope. One of these episodes could be documented, and revealed symptomatic bradycardia suspicious of

Introduction Documented symptomatic bradycardia due to irreversible cause is considered a class I indication for pacing [1, 2]. Here, we present a patient suffering from bradycardia-related presyncope suspicious of sinus node arrest, in whom a pheochromocytoma was revealed.

Case report A male patient, 46 years of age (height 174 cm/weight 73 kg) with a recent history of intermittent palpitations, headache, angina-like chest pain and two episodes of presyncope was admitted to a general hospital. No history of hypertension could be obtained. Physical examination, ECG and routine lab© 1997 Blackwell Science Ltd

sinus node arrest. Due to hints of an elevated sympathetic tone (Schellong test, circadian blood pressure pattern without diurnal rhythm) 24-h urinary catecholamine concentrations were measured and found increased. MIBG-scintigraphy and abdominal- computed tomography indicated the location of the pheochromocytoma. After removal of the tumour, no further episodes of presyncopes or bradydysrhythmias were observed. Keywords: ambulatory blood pressure monitoring, MIBG-scintigraphy, pheochromocytoma, Schellong test, sinus node arrest.

oratory findings were within the physiologic range. Minutes before a scheduled bicycle ergometer testing the patient underwent a sudden attack of nausea, bradycardia and dizziness. Blood pressure was 120/80 mmHg. The ECG showed no p-waves, suggesting sinus node arrest or complete sinuatrial block and a slow irregular wide QRS escape rhythm (cycle length between 900 and 1276 ms) (Fig. 1). Restoration of sinus rhythm occurred without intervention, and the patient was transferred to the department of cardiology for further evaluation. Another bicycle ergometer stress-test revealed both normal heart rate and blood pressure values without any signs or symptoms of ischaemia. Echocardiography showed physiological dimensions of all heart chambers, no valve dysfunction and no signs of left ventricular hypertrophy (left ventricular mass 249

250

R. ZWEIKER et al.

5 mm/mV

10 mm/mV V1

I

V2

II

V3

III aVR

V4

aVL

V5

aVF 50 mm/s

V6 0.25–25 Hz UHL Heinrich

Schiller Switzerland

Fr 06.Jan.95 12:32:57 AT–6 S 6.2

50 mm/s

0.25–25 Hz UHL Heinrich Schiller Switzerland

Fr 06.Jan.95 12:32:57 AT–6 S 6.2

Fig. 1 12-lead ECG after recovery. Sinus rhythm is suddenly blocked. The block is escaped by a ventricular escape beat. Restoration of sinus rhythm (a) followed by a supraventricular ectopic beat. Two further escape beats (left bundle branch block pattern), intermittent reoccurrence of sinus rhythm followed by another escape beat of the same pattern.

93 gm22). Twenty-four-hour ECG monitoring recorded some supraventricular and ventricular ectopic beats (Lown-classification stage I), but no episodes of bradycardia. Ambulatory blood pressure monitoring evaluated normotension (mean 24-h blood pressure 121/84; mean daytime blood pressure 122/86; mean night-time blood pressure 114/78 mmHg), but the circadian blood pressure pattern did not show a reduction of blood pressure during night-time (Fig. 2). Maximum blood pressure was 163/95 mmHg. Invasive investigations comprised coronary angiography, right and left heart catheterization and electrophysiological study. Pathological results were not obtained. Schellong test showed a decrease of systolic and an increase of diastolic blood pressure, as well as an increase in heart rate after changing from supine to upright position. Due to this observation and the nondipping pattern of blood pressure during sleep, 24-h urine analysis was performed three times. Highpressure liquid chromatography revealed elevated values of adrenalin (92 micrograms 24 h21; normal range below 20 micrograms 24 h21), noradrenalin (459 micrograms 24 h21; normal range below 100 micrograms 24 h21) and dopamine (547 micrograms 24 h21; normal range below 250 micrograms 24 h21) suggesting a catecholamine-producing tumour. Metaiodobenzyl–guanidin scintigraphy showed an area with high tracer activity in the left suprarenal region (Fig. 3). Abdominal computed tomography confirmed a tumour sized 6:5:5 cm with central cystic changes in the left adrenal gland (Fig. 4). Surgical removal was performed without complications. Histopathological examination including immuno-histochemistry for chromogranine A proved the diagnosis of a benign pheochromocytoma (Figs 5 and 6). There was no evidence of extensive local or vascular invasion, confluent necrosis or a high mitotic rate. Furthermore, a

diploid DNA-index of 1.0 was determined by flow cytometry [3]. Para-aortal lymphatic nodes were unaffected. A one-year follow-up period was unremarkable. Twenty-four-hour catecholamine concentrations at follow-up were within the physiological range as well as the results of 24-h blood pressure monitoring and abdominal-computed tomography. Since the removal of the tumour, no episodes of symptomatic bradycardia or dizziness have been observed in our patient.

Discussion Pheochromocytoma is a rare, but still life-threatening disorder in the general population with an incidence of 1:100 000 inhabitants year21 [4]. In hypertensives 0.05–0.2% of the patients are affected. Symptoms result from inappropriate excess-secretion of noradrenalin and/or adrenalin and dopamine [5]. The most frequent symptoms are palpitations, severe sweating and headache [6]. Intermittent or persistent hypertension, especially in terms of hypertensive urgencies and emergencies present in up to 78% of the patients, are the most important symptoms. Catecholamine-secreting tumours are often accompanied by imbalances of the autonomic nervous system. Symptoms of autonomic dysregulation comprise orthostatic hypotension, reflex tachycardia and impairment of the baroreflex-sensitivity [7], but also a loss of the regular circadian blood pressure rhythm (nondipping pattern) [8]. Catecholaminecardiomyopathy due to toxic effects of adrenalin and noradrenalin is also a well-known feature of pheochromocytoma [9]. Cardiac failure and abnormalities in cardiac impulse generation and conduction are clinical manifestations of catecholaminecardiomyopathy. In our patient signs of cardiomy© 1997 Blackwell Science Ltd Journal of Internal Medicine 242: 249–253

CASE REPORT: PRESYNCOPE, PHEOCHROMOCYTOMA

Fig. 2 Circadian blood pressure pattern. Upper part: Average hourly blood pressure values (Spacelabs 90207) before surgical removal of the pheochromocytoma; nondipping pattern. Mean 24-hBP: 121/84 mmHg. Mean daytimeBP: 122/86 mmHg Mean nighttime-BP: 114/78 mmHg. Lower part: Average hourly blood pressure values (Spacelabs 90207) after surgical removal of the pheochromocytoma; dipping pattern. Mean 24-h-BP: 113/82 mmHg. Mean daytime-BP: 118/86 mmHg. Mean night-timeBP: 98/66 mmHg. (BP 5 blood pressure).

260 240 220 200 180 160 140 120 100 80 60 40 200 180 160 140 120 100 80 60 40 20

251

Average hourly blood pressure

20

22

0

4

2

8

6

10

12

14

16

18

Time

260 240 220 200 180 160 140 120 100 80 60 40 200 180 160 140 120 100 80 60 40 20

Systolic

10

12

14

16

Diastolic

18

20

22

MAP

0

Heart rate

2

4

6

8

10

Time opathy were excluded by means of cardiac catheterization and electrophysiological study. Symptoms of autonomic imbalance were evaluated by Schellong testing and ambulatory blood pressure monitoring, which showed an impaired circadian blood pressure pattern. After resection of the tumour, the physiologic night decline of blood pressure (dipping) reappeared. The Schellong-test was not repeated. © 1997 Blackwell Science Ltd Journal of Internal Medicine 242: 249–253

Scintigraphy using meta-iodobenzyl–guanidine (MIBG), a drug, which selectively accumulates in adrenergic tissues, offers a safe and reliable localization of the tumour with sensitivity of 85% and a specificity of more than 90% [10]. Computed tomography provides important additional information. Causal treatment can be achieved by surgical resection of the tumour under adrenergic blockade.

252

R. ZWEIKER et al.

Fig. 3 Meta-iodobenzyl–guanidin-scintigraphy showing an area with high tracer activity in the left suprarenal region.

Further follow-up is important, because reoccurrence of the disease has been reported even after ten years [11]. Bradycardia without any atrial electrical activity is considered as one feature of the sick-sinus syndrome. This clinical entity is often due to myocardial damage (myocarditis, myocardial infarction, cardiac tumour), carotid hypersensitivity, hyper/hypokalaemia or drugs. All of those mechanisms were excluded in the presented patient. But disturbances of the autonomic nervous system are also able to influence sinus node function. After removal of the tumour, the described patient has had no further signs of bradycardia or dizziness. According to the results of the initial electrophysiological study [12] assessing the sinus node recovery time at baseline, no permanent sinus node dysfunction was observed. Hence, an invasive proof sinus node arrest cannot be provided, even if the surface-ECG tracing is suspicious of sinus node arrest.

Fig. 5 Encapsulated, partially cystic tumour, largest diameter 4.5 centimetres.

Fig. 6 Alveolar arrangement of tumour cells characteristic for pheochromocytoma.

It is concluded that the observed episode of bradycardia-related presyncope was due to transient autonomic dysregulation caused by intermittent excess-secretion of catecholamines. To our knowledge, this is the first report of this distinct clinical feature in a patient suffering from pheochromocytoma.

References

Fig. 4 Abdominal-computed tomography showing a tumour sized 6:5:5 cm with central cystic changes in the left adrenal gland.

1 Dreifus LS, Fisch C, Griffin JC, Gillette P, Mason JW, Parsonnet V. Guidelines for implantation of cardiac pacemakers and antiarrhythmic devices. J Am Coll Cardiol 1991; 18: 1–13. 2 Kusumoto FM, Goldschlager N. Cardiac pacing. New Engl J Med 1996; 334: 89–98. 3 Polak JM. Pheochromocytoma. In: Polak JM ed. Diagnostic Histopathology of Neuroendocrine Tumours. Edinburgh: Churchill Livingstone, 1993; 210–26. 4 Beard CM, Sheps SG, Kurland LT, Carney JA, Lie JT. Occurrence of pheochromocytoma in Rochester, Minnesota, 1950 through 1979. Mayo Clin Proc 1983; 58: 802–4. © 1997 Blackwell Science Ltd Journal of Internal Medicine 242: 249–253

CASE REPORT: PRESYNCOPE, PHEOCHROMOCYTOMA

5 Manger WM, Gifford Jr RW. Pheochromocytoma: a clinical overview. In: Laragh JH, Brenner BM eds. Hypertension: Pathophysiology, Diagnosis and Management, 2nd edn. New York, USA: Raven Press, Ltd., 1995; 2225–44. 6 Schurmeyer TH, Engeroff B, von zur Mühlen A, Dralle H. Symptomatik und endokrinologische befunde bei katecholamin-sezernierenden tumoren. Ergebnisse bei 106 konsekutiven Patienten. DMW 1994; 119 (50): 1721–7. 7 Bletry O. Aspects etiologiques des hypotensions orthostatiques. Rev Med Intern 1992; 13(6): 430– 7 (in French). 8 Meisel SR, Moravi V, Rosenthal T, Akselrod S. Spectral analyses of the systolic blood pressure signal in secondary hypertension. J Hypertens 1994; 12(3): 269–75. 9 Wood R, Commerford PJ, Rose AG, Tooke A. Reversible catecholamine-induced cardiomyopathy. Am Heart J 1991; 119: 610–13.

© 1997 Blackwell Science Ltd Journal of Internal Medicine 242: 249–253

253

10 Sisson JC, Frager MS, Valk TW, Gross MD, Swanson DP, Wieland DM et al. Scintigraphic localisation of pheochromocytoma. N Engl J Med 1981; 305: 12–17. 11 Gibbons CE, Kashif KM, Lewi HJ. Paraganglionic pheochromocytoma presenting twelve years after adrenalectomy. Eur Urol 1995; 27(3): 264–5. 12 Breithardt G. Prüfung der Sinusknotenfunktion. In: Seipel L, Borggrefe M, Breithardt G, Ostermeyer J, eds. Klinische Elektrophysiologie des Herzens. New York, USA; Stuttgart, Germany: Georg Thieme Verlag 1987; 22–46 (in German). Received 18 April 1996; accepted 5 February 1997. Correspondence: Robert Zweiker MD, Department of Internal Medicine, Division of Cardiology, Karl-Franzens-University, Auenbruggerplatz 15, A–8036 Graz, Austria (fax: 143/316/385/3062).