American Journal of Emergency Medicine 33 (2015) 311.e3–311.e5
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case Report
Recurrence and metastasis of pheochromocytoma mimic acute ST-segment elevation myocardial infarction: a case report Abstract Pheochromocytomas are cathecholamine-secreting tumor and may present with numerous of general symptoms, such as hypertension, pallor, headache tachycardia, chest pain, and cold sweating. Cardiac manifestations include typical angina, electrocardiographic change, and elevated cardiac biomarker. Transient systolic dysfunction of the left ventricle sometimes may happen with, the worst, heart failure and cardiogenic shock, in a similar manner of apical ballooning syndrome (Tokotsubo or stress cardiomyopathy) and mimics ST-segment elevation myocardial infarction. Here, we presented a case with past medical record of pheochromocytoma status postsuccessful surgical adrenalectomy many years ago, and she came to the emergency department with angina symptom. As first presentation of acute coronary syndrome via symptoms, electrocardiographic change, and elevated cardiac biomarkers, she underwent coronary angiography. No significant coronary occlusion but regional wall motion abnormality was found. However, a big adrenal mass in the left abdomen and multiple hepatic radiolucent lesions were detected accidentally by the meanwhile computed tomography that supposed to rule out the acute aortic syndrome. Recurrent pheochromocytoma with cathecholamine-related stress cardiomyopathy was confirmed thereafter. Apical ballooning syndrome (ABS), also called stress cardiomyopathy or Tokotsubo cardiomyopathy, is not a rare condition at emergency department. It counts for 0.7% to 2.5% of patient who suspected of acute coronary syndrome (ACS). And almost 90% of them are female with a triggering event [1]. Conversely, the cathecholamine-secreting pheochromocytoma is relatively rare, and it would act as a similar mechanism to ABS that may lead to transient left ventricular systolic dysfunction and mimics ACS [2, 3]. A 54-year-old woman came to the emergency department with intermittent chest tightness, severe cold sweating, upper back pain, and palpitation that persisted for at least 2 days. Initial physical examination revealed alert consciousness but lethargy, tachycardia, and mildly elevated blood pressure. She has had medical history of pheochromocytoma of the left adrenal gland status postsurgical resection 13 years ago. No other remarkable systemic disease could be traced except for stage I hypertension without medical control for 1 to 2 years. The electrocardiogram revealed sinus tachycardia, pathologic Q wave, ST-segment elevation, and biphasic T wave over the leads V1 to V3 with no reciprocal change. Preliminary echocardiography was performed with regional wall motion abnormality over the apical and midseptal wall of left ventricle with depressed systolic function (the ejection fraction estimated to be 40%). The symptoms persisted even with antiangina therapy, and the cardiac biomarkers were mildly elevated. Under the impression of ACS, considering acute anteroseptal ST-segment elevation myocardial infarction, the cardiac catheteriza0735-6757/© 2014 Elsevier Inc. All rights reserved.
tion with coronary angiography was performed with no significant coronary stenosis found. The left ventriculography confirmed the abnormal finding of echocardiography that formed a ballooning pattern (Fig. 1). The computed tomography of chest and abdomen, which ordered for ruling out acute aortic syndrome, accidentally, detected 1 large mass over the left adrenal site and multiple masses over the lobes of liver in the meantime. With past medical record of adrenal tumor, recurrence of the pheochromocytoma with distant metastases was highly suspected. In the coming days of hospitalization, tissue biopsy of hepatic mass was performed and concluded neuroendocrine tumor. The value of 24-hour urine vanillylmandelic acid was extremely high (70 mg/24 hours; normal reference,: 1.0-7.5mg/24 hours). With the finding above, diagnosis of recurrence of the pheochromocytoma, left adrenal gland with distant metastases to the liver was made. The following echocardiography after 7 days showed total recovery of the left ventricular systolic function without regional wall motion defect (Fig. 2). With the dynamic regression of the function, stress cardiomyopathy with ABS was confirmed. Pheochromocytomas are cathecholamine-secreting neuroectodermal tumors and surgically curable. However, they could also be lethal if the diagnosis is not early made. The incidence is approximately 1 to 8/million in general population. They are commonly arising from adrenal medulla and could be single, multiple, or extraadrenal. [2, 4] The mortality rate had been declined (1.7%-2%) due to much more understanding of the cathecholamine physiology [1, 2]. Patients may present with general symptoms, such as palpitation, pulsatile hypertension, pallor, headache, cold sweating, and anxiety. Most patients with pheochromocytomas have normal left ventricular systolic function, but around 10% of them may present with cathecholamine-related cardiomyopathy [5]. The mechanisms of the transient systolic dysfunction are still uncertain. The hypothesis includes oversecreting cathecholamine, epinephrine, and especially, the norepinephrine that would induce microvascular dysfunction, multiple epicardial spasm, and direct impact of the cardiac myocytes. The high-circulating level of norepinephrine would trigger a switch in intracellular signal trafficking in ventricular myocytes, from β2 adrenergic receptor G stimulatory protein to β2 adrenergic receptor G inhibitory protein. The switch is supposed to protect the myocytes from proapoptotic effect, which might be induced by intense activation of β-adrenoceptor and hence leads to a negatively inotropic effect [6, 7, 8]. It is most apparent in the anterior wall and apical septum rather than the basal part of left ventricle. Thus, ABS happens and may mimic ACS clinically diagnosed at emergency department by typical angina, electrocardiographic ST-segment change, and elevated cardiac biomarker. The abnormal motion of myocardium would return to normal status within days to weeks, in a similar manner of myocardial stunning that is induced by true coronary stenosis.
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T.-H. Yang, W.-C. Tsai / American Journal of Emergency Medicine 33 (2015) 311.e3–311.e5
personal or family history. With early diagnosis, the primary pheochromocytoma is a surgically curable disease. But if delayed, it leads to high mortality rate. Tsung-Han Yang, MD Division of Cardiology Department of Internal Medicine Kaohsiung Armed Forces General Hospital, Tsoying Branch Kaohsiung, Taiwan Division of Cardiology, Department of Internal Medicine Tri-Service General Hospital National Defense Medical Center Taipei, Taiwan Wei-Che Tsai, MD Division of Cardiology, Department of Internal Medicine Tri-Service General Hospital, National Defense Medical Center Taipei, Taiwan Corresponding author. No. 325, Sec.2, Cheng-gong Rd. Neihu District, Taipei City 114, Taiwan (ROC) E-mail address: [email protected]
Fig. 1. Left ventriculography in end-systolic phase showed normal systolic function in basal part of ventricle but severely hypokinetic in middle and apical segments, which seems ballooning.
The test with highest sensitivity for diagnosis of pheochromocytoma is to measure the plasma level of free metanephrines (99%), and the specificity was highest with urinary vanillylmandelic acid (95%) [9]. Elective surgery is the best and curable way in the primary pheochromocytoma and even with malignancy. But, in latter, the recurrence and metastases may occur years after. In our patient, the metastatic tumors could be treated with iodine 131 metaidobenzylguanidine therapy or chemotherapy for the relief of the symptom. However, the overall prognosis and response to therapy are poor [10]. In patients presenting ABS at emergency department, especially without emotional or physical stress, prompt investigations of possible neuroendocrine tumors are always necessary even without previous
A
http://dx.doi.org/10.1016/j.ajem.2014.08.010
References [1] Pilgrim Thomas M, Wyss Thomas R. Takotsubo cardiomyopathy or transient left ventricular apical ballooning syndrome: a systematic review. Int J Cardiol 2008; 124(3):283–92. [2] Subramaniam Rajeshwari. Pheochromocytoma—current concepts in diagnosis and management. Trends Anaesth Crit Care 2011;1(2):104–10. [3] Galetta F, Franzoni F, Bernini G, Poupak F, Carpi A, Cini G, et al. Cardiovascular complications in patients with pheochromocytoma: a mini-review. Biomed Pharmacother 2010;64(7):505–9. [4] Sutton MG, Sheps SG, Lie JT. Prevalence of clinically unsuspected pheochromocytoma. Review of a 50-year autopsy series. Mayo Clin Proc 1981;56(6):354–60.
B
C
D
Fig. 2. Echocardiography. Hypokinesia in apical and middle wall of left ventricle during the end-systole phase (parasternal long axis view [A], apical 4-chamber view [B]). C and D, Recovery of the systolic function with no regional motion abnormality.
T.-H. Yang, W.-C. Tsai / American Journal of Emergency Medicine 33 (2015) 311.e3–311.e5 [5] Park JH, Kim KS, Sul JY, Shin SK, Kim JH, Lee JH, et al. Prevalence and patterns of left ventricular dysfunction in patients with pheochromocytoma. J Cardiovasc Ultrasound 2011;19(2):76–82. [6] Lyon Alexander R, Rees Paul SC, Prasad Sanjay, Poole-Wilson Philip A, Harding Sian E. Stress (Takotsubo) cardiomyopathy—a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat Clin Pract Cardiovasc Med 2008;5(1):23–9. [7] Gianni Monica, Dentali Francesco, Maria Grandi Anna, Sumner Glen, Hiralal Rajesh, Lonn Eva. Apical ballooning syndrome or takotsubo cardiomyopathy: a systematic review. Eur Heart J 2006;27:1523–9.
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[8] Bybee Kevin A, Kara Tomas, Prasad Abhiram, Lerman Amir, Barsness Greg W, Scott Wright R, et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med 2004;141(11):858–65. [9] Lenders Jacques WM, Pacak Karel, Walther McClellan M, Marston Linehan W, Mannelli Massimo, Friberg Peter, et al. Biochemical diagnosis of pheochromocytoma: which test is best. JAMA 2002;287(11):1427–34. [10] Schlumberger M, Gicquel C, Lumbroso J, Tenenbaum F, Comoy E, Bosq J, et al. Malignant pheochromocytoma: clinical, biological, histologic and therapeutic data in a series of 20 patients with distant metastases. J Endocrinol Invest 1992;15(9):631–42.
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case Report
Recurrence and metastasis of pheochromocytoma mimic acute ST-segment elevation myocardial infarction: a case report Abstract Pheochromocytomas are cathecholamine-secreting tumor and may present with numerous of general symptoms, such as hypertension, pallor, headache tachycardia, chest pain, and cold sweating. Cardiac manifestations include typical angina, electrocardiographic change, and elevated cardiac biomarker. Transient systolic dysfunction of the left ventricle sometimes may happen with, the worst, heart failure and cardiogenic shock, in a similar manner of apical ballooning syndrome (Tokotsubo or stress cardiomyopathy) and mimics ST-segment elevation myocardial infarction. Here, we presented a case with past medical record of pheochromocytoma status postsuccessful surgical adrenalectomy many years ago, and she came to the emergency department with angina symptom. As first presentation of acute coronary syndrome via symptoms, electrocardiographic change, and elevated cardiac biomarkers, she underwent coronary angiography. No significant coronary occlusion but regional wall motion abnormality was found. However, a big adrenal mass in the left abdomen and multiple hepatic radiolucent lesions were detected accidentally by the meanwhile computed tomography that supposed to rule out the acute aortic syndrome. Recurrent pheochromocytoma with cathecholamine-related stress cardiomyopathy was confirmed thereafter. Apical ballooning syndrome (ABS), also called stress cardiomyopathy or Tokotsubo cardiomyopathy, is not a rare condition at emergency department. It counts for 0.7% to 2.5% of patient who suspected of acute coronary syndrome (ACS). And almost 90% of them are female with a triggering event [1]. Conversely, the cathecholamine-secreting pheochromocytoma is relatively rare, and it would act as a similar mechanism to ABS that may lead to transient left ventricular systolic dysfunction and mimics ACS [2, 3]. A 54-year-old woman came to the emergency department with intermittent chest tightness, severe cold sweating, upper back pain, and palpitation that persisted for at least 2 days. Initial physical examination revealed alert consciousness but lethargy, tachycardia, and mildly elevated blood pressure. She has had medical history of pheochromocytoma of the left adrenal gland status postsurgical resection 13 years ago. No other remarkable systemic disease could be traced except for stage I hypertension without medical control for 1 to 2 years. The electrocardiogram revealed sinus tachycardia, pathologic Q wave, ST-segment elevation, and biphasic T wave over the leads V1 to V3 with no reciprocal change. Preliminary echocardiography was performed with regional wall motion abnormality over the apical and midseptal wall of left ventricle with depressed systolic function (the ejection fraction estimated to be 40%). The symptoms persisted even with antiangina therapy, and the cardiac biomarkers were mildly elevated. Under the impression of ACS, considering acute anteroseptal ST-segment elevation myocardial infarction, the cardiac catheteriza0735-6757/© 2014 Elsevier Inc. All rights reserved.
tion with coronary angiography was performed with no significant coronary stenosis found. The left ventriculography confirmed the abnormal finding of echocardiography that formed a ballooning pattern (Fig. 1). The computed tomography of chest and abdomen, which ordered for ruling out acute aortic syndrome, accidentally, detected 1 large mass over the left adrenal site and multiple masses over the lobes of liver in the meantime. With past medical record of adrenal tumor, recurrence of the pheochromocytoma with distant metastases was highly suspected. In the coming days of hospitalization, tissue biopsy of hepatic mass was performed and concluded neuroendocrine tumor. The value of 24-hour urine vanillylmandelic acid was extremely high (70 mg/24 hours; normal reference,: 1.0-7.5mg/24 hours). With the finding above, diagnosis of recurrence of the pheochromocytoma, left adrenal gland with distant metastases to the liver was made. The following echocardiography after 7 days showed total recovery of the left ventricular systolic function without regional wall motion defect (Fig. 2). With the dynamic regression of the function, stress cardiomyopathy with ABS was confirmed. Pheochromocytomas are cathecholamine-secreting neuroectodermal tumors and surgically curable. However, they could also be lethal if the diagnosis is not early made. The incidence is approximately 1 to 8/million in general population. They are commonly arising from adrenal medulla and could be single, multiple, or extraadrenal. [2, 4] The mortality rate had been declined (1.7%-2%) due to much more understanding of the cathecholamine physiology [1, 2]. Patients may present with general symptoms, such as palpitation, pulsatile hypertension, pallor, headache, cold sweating, and anxiety. Most patients with pheochromocytomas have normal left ventricular systolic function, but around 10% of them may present with cathecholamine-related cardiomyopathy [5]. The mechanisms of the transient systolic dysfunction are still uncertain. The hypothesis includes oversecreting cathecholamine, epinephrine, and especially, the norepinephrine that would induce microvascular dysfunction, multiple epicardial spasm, and direct impact of the cardiac myocytes. The high-circulating level of norepinephrine would trigger a switch in intracellular signal trafficking in ventricular myocytes, from β2 adrenergic receptor G stimulatory protein to β2 adrenergic receptor G inhibitory protein. The switch is supposed to protect the myocytes from proapoptotic effect, which might be induced by intense activation of β-adrenoceptor and hence leads to a negatively inotropic effect [6, 7, 8]. It is most apparent in the anterior wall and apical septum rather than the basal part of left ventricle. Thus, ABS happens and may mimic ACS clinically diagnosed at emergency department by typical angina, electrocardiographic ST-segment change, and elevated cardiac biomarker. The abnormal motion of myocardium would return to normal status within days to weeks, in a similar manner of myocardial stunning that is induced by true coronary stenosis.
311.e4
T.-H. Yang, W.-C. Tsai / American Journal of Emergency Medicine 33 (2015) 311.e3–311.e5
personal or family history. With early diagnosis, the primary pheochromocytoma is a surgically curable disease. But if delayed, it leads to high mortality rate. Tsung-Han Yang, MD Division of Cardiology Department of Internal Medicine Kaohsiung Armed Forces General Hospital, Tsoying Branch Kaohsiung, Taiwan Division of Cardiology, Department of Internal Medicine Tri-Service General Hospital National Defense Medical Center Taipei, Taiwan Wei-Che Tsai, MD Division of Cardiology, Department of Internal Medicine Tri-Service General Hospital, National Defense Medical Center Taipei, Taiwan Corresponding author. No. 325, Sec.2, Cheng-gong Rd. Neihu District, Taipei City 114, Taiwan (ROC) E-mail address: [email protected]
Fig. 1. Left ventriculography in end-systolic phase showed normal systolic function in basal part of ventricle but severely hypokinetic in middle and apical segments, which seems ballooning.
The test with highest sensitivity for diagnosis of pheochromocytoma is to measure the plasma level of free metanephrines (99%), and the specificity was highest with urinary vanillylmandelic acid (95%) [9]. Elective surgery is the best and curable way in the primary pheochromocytoma and even with malignancy. But, in latter, the recurrence and metastases may occur years after. In our patient, the metastatic tumors could be treated with iodine 131 metaidobenzylguanidine therapy or chemotherapy for the relief of the symptom. However, the overall prognosis and response to therapy are poor [10]. In patients presenting ABS at emergency department, especially without emotional or physical stress, prompt investigations of possible neuroendocrine tumors are always necessary even without previous
A
http://dx.doi.org/10.1016/j.ajem.2014.08.010
References [1] Pilgrim Thomas M, Wyss Thomas R. Takotsubo cardiomyopathy or transient left ventricular apical ballooning syndrome: a systematic review. Int J Cardiol 2008; 124(3):283–92. [2] Subramaniam Rajeshwari. Pheochromocytoma—current concepts in diagnosis and management. Trends Anaesth Crit Care 2011;1(2):104–10. [3] Galetta F, Franzoni F, Bernini G, Poupak F, Carpi A, Cini G, et al. Cardiovascular complications in patients with pheochromocytoma: a mini-review. Biomed Pharmacother 2010;64(7):505–9. [4] Sutton MG, Sheps SG, Lie JT. Prevalence of clinically unsuspected pheochromocytoma. Review of a 50-year autopsy series. Mayo Clin Proc 1981;56(6):354–60.
B
C
D
Fig. 2. Echocardiography. Hypokinesia in apical and middle wall of left ventricle during the end-systole phase (parasternal long axis view [A], apical 4-chamber view [B]). C and D, Recovery of the systolic function with no regional motion abnormality.
T.-H. Yang, W.-C. Tsai / American Journal of Emergency Medicine 33 (2015) 311.e3–311.e5 [5] Park JH, Kim KS, Sul JY, Shin SK, Kim JH, Lee JH, et al. Prevalence and patterns of left ventricular dysfunction in patients with pheochromocytoma. J Cardiovasc Ultrasound 2011;19(2):76–82. [6] Lyon Alexander R, Rees Paul SC, Prasad Sanjay, Poole-Wilson Philip A, Harding Sian E. Stress (Takotsubo) cardiomyopathy—a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat Clin Pract Cardiovasc Med 2008;5(1):23–9. [7] Gianni Monica, Dentali Francesco, Maria Grandi Anna, Sumner Glen, Hiralal Rajesh, Lonn Eva. Apical ballooning syndrome or takotsubo cardiomyopathy: a systematic review. Eur Heart J 2006;27:1523–9.
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[8] Bybee Kevin A, Kara Tomas, Prasad Abhiram, Lerman Amir, Barsness Greg W, Scott Wright R, et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med 2004;141(11):858–65. [9] Lenders Jacques WM, Pacak Karel, Walther McClellan M, Marston Linehan W, Mannelli Massimo, Friberg Peter, et al. Biochemical diagnosis of pheochromocytoma: which test is best. JAMA 2002;287(11):1427–34. [10] Schlumberger M, Gicquel C, Lumbroso J, Tenenbaum F, Comoy E, Bosq J, et al. Malignant pheochromocytoma: clinical, biological, histologic and therapeutic data in a series of 20 patients with distant metastases. J Endocrinol Invest 1992;15(9):631–42.
