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CASE REPORT
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Paraganglioma-induced Alveolar Hemorrhage Yosuke Makuuchi 1, Mikio Wada 1, Atsushi Kawashima 1, Yu Kataoka 1, Masahito Miyahara 2, Masatomi Ikusaka 2 and Keizo Kagawa 1
Abstract A 21-year-old man twice developed sudden dyspnea during running examinations for promotion. Chest computed tomography (CT) revealed lobular ground-glass opacity and centrilobular shadows bilaterally. The bronchoscopy findings were consistent with alveolar hemorrhage, and echocardiography showed severe hypokinesia a few hours later. A mass was subsequently identified along the abdominal aorta on enhanced CT and iodine-131 metaiodobenzylguanidine scintigraphy. Catecholamine oversecretion, which was later confirmed, may have increased the pulmonary vein pressure, thus resulting in the development of an alveolar hemorrhage, and damaged the cardiac muscles as manifested by hypokinesia. Since the patient had not previously developed alveolar hemorrhage during usual exercise, emotional stress superimposed on the physical activity may have triggered the paraganglioma to secrete excessive catecholamines, thus resulting in the observed symptoms. Key words: alveolar hemorrhage, paraganglioma, catecholamine oversecretion (Intern Med 54: 487-489, 2015) (DOI: 10.2169/internalmedicine.54.2304)
Introduction Diffuse alveolar hemorrhage is a life-threatening syndrome that may cause respiratory failure. Histologically, alveolar hemorrhage can be classified into three types: 1) pulmonary capillaritis, 2) diffuse alveolar damage, including that associated with connective tissue disease, vasculitis, infection and drug intoxication and 3) bland pulmonary hemorrhage without inflammation (1). There are only a few reports of the onset of alveolar hemorrhage following exercise (2, 3) or induced by pheochromocytoma (4-7). However, the mechanisms underlying the development of alveolar hemorrhage remain unclear. We herein report a case of exercise-induced alveolar hemorrhage resulting from excessive emotional stress, which led to catecholamine oversecretion from a paraganglioma and the consequent development of symptoms.
Case Report A 21-year-old male self-defense force member visited our emergency room with sudden chest pain and hemoptysis
that occurred during a running examination for a promotion. His blood pressure on arrival was 140/80 mmHg, with a pulse rate of 90/min, respiratory rate of 42/min and oxygen saturation of 84% without oxygen therapy. Coarse crackles were audible bilaterally during breathing. Blood test findings (e.g., coagulation, inflammation and immune reactions) were normal. A chest X-ray showed bilateral infiltrative shadows, and computed tomography (CT) revealed lobular groundglass opacity and centrilobular shadows (Fig. 1). Although the possibility of acute congestive heart failure was considered, an electrocardiogram and transthoracic echocardiography revealed no abnormalities. We therefore suspected alveolar hemorrhage and transferred the patient to a higher level medical institution. Although the bronchoalveolar lavage fluid was bloody, which supported our diagnosis, we were unable to determine the cause of the patient’s symptoms. Several hours after admission, his blood pressure suddenly dropped, and echocardiography demonstrated severe cardiac wall motion abnormalities, including a left ventricular dimension diastolic/systolic of 52 mm/42 mm and ejection fraction of 35%, with the absence of valvular disease. These abnormalities improved the next day, and the patient’s respiratory condition
１
General Internal Medicine, Fukuchiyama City Hospital, Japan and ２Department of General Medicine, Chiba University Hospital, Japan Received for publication December 12, 2013; Accepted for publication July 13, 2014 Correspondence to Dr. Mikio Wada, [email protected]
487
Intern Med 54: 487-489, 2015
DOI: 10.2169/internalmedicine.54.2304
Figure 1. Image showing bilateral lobular ground-glass opacity and centrilobular shadows.
Figure 3. Image showing an intense uptake on iodine-131 MIBG scintigraphy.
recovered within a few days. He was discharged on day 5 of hospitalization. Despite concerns that the alveolar hemorrhage may recur with exercise, he continued training uneventfully. Five months after discharge, the patient was brought to our emergency room with dyspnea that had presented during another running examination for a promotion. Unlike the first visit, no hemoptysis was observed. His blood pressure was 101/45 mmHg, with a pulse rate of 65/min and his oxygen saturation 100% with 12 L of oxygen. The results of blood tests were again normal. The patient’s breath sounds, chest X-ray and CT findings were similar to those noted on the first visit. Echocardiogram revealed slight mitral regurgitation. These imaging findings and the patient’s medical history led us to suspect recurrence of alveolar hemorrhage. His blood pressure subsequently dropped temporarily after admission; however, he recovered within a few days and was discharged before receiving a final diagnosis. We conferred with other institutions regarding the cause
Figure 2. Image showing a mass along the abdominal aorta (white arrowheads).
of the alveolar hemorrhage in this case. Nevertheless, no differential diagnoses other than acute heart failure without valvular disease were made. Enhanced CT disclosed a mass in the abdominal aorta (Fig. 2). We therefore considered the possibility of the abrupt onset of left heart failure due to catecholamine oversecretion, and consequently confirmed an intense uptake in the mass on iodine-131 metaiodobenzylguanidine (MIBG) scintigraphy (Fig. 3). Two months after the second attack, the oversecretion of catecholamines, except for epinephrine, was confirmed on a 24-hour urine test: epinephrine, 0.008 mg/day (normal range: 0.003-0.04 mg/ day); norepinephrine, 1.75 mg/day (normal range: 0.0310.160 mg/day); and dopamine, 1.26 mg/day (normal range: 0.280-1.10 mg/day). During hospitalization for these tests, the patient exhibited no symptoms and was confirmed to not have hypertension or diabetes. The final diagnosis was a symptomatic paraganglioma; After we told the diagnosis of “paraganglioma” to the patient, it came to our attention that his father was operated on for paraganglioma seven years ago as his family medical history. The current patient’s paraganglioma was surgically removed, and his condition has since remained satisfactory.
Discussion The present case relates to bland pulmonary hemorrhage with a hemodynamic cause resulting from paraganglioma. Alveolar hemorrhage may be triggered by infectious and/or connective tissue diseases, as well as other causes. However, the possibility of an infectious or connective tissue disease was excluded in the present case based on the patient’s test results. A diagnosis of valvular disease was also excluded, given the results of echocardiography performed after the patient’s symptoms improved. Not all patients with pheochromocytoma, including our patient, exhibit continuous hypertension (8-11). Excessive catecholamine secretion can induce sudden blood pressure elevation, which in turn can lead to temporal left ventricular
488
Intern Med 54: 487-489, 2015
DOI: 10.2169/internalmedicine.54.2304
wall motion deficiency (5, 9, 10, 12). The present patient displayed transient cardiac wall motion abnormalities a few hours after the onset of symptoms. Hard exercise and sudden blood pressure elevation have the potential to increase the pulmonary vein pressure and pulmonary wedge pressure (13, 14). In rabbit models, an increased capillary pressure has been shown to induce alveolar hemorrhage (15). Therefore, the combination of excessive catecholamine secretion and exercise may trigger the development of lung edema. Emotional stress has also been reported to increase catecholamine secretion (16). Catecholamine-producing tumors, such as pheochromocytomas, secrete excessive amounts of catecholamines in response to stress resulting from exercise and/or emotional excitation (17). The present patient’s symptoms did not develop during routine selfdefense force training, but rather occurred during two separate examinations for promotion, suggesting that extreme emotional stress may have played a role in the pathogenesis in this case. Indeed, the patient did not have an underlying heart disease, although he suffered from transient cardiac insufficiency during both examinations. The above observations suggest the presence of catecholamine oversecretion due to excessive emotional stress superimposed on heavy exercise, which subsequently induced an abrupt increase in the pulmonary venous pressure associated with alveolar hemorrhage in this patient with paraganglioma. The authors state that they have no Conflict of Interest (COI).
References 1. Lara AR, Schwarz MI. Diffuse alveolar hemorrhage. Chest 137: 1164-1171, 2010. 2. Weiler-Ravell D, Shupak A, Goldenberg I, et al. Pulmonary oedema and haemoptysis induced by strenuous swimming. BMJ
311: 361-362, 1995. 3. Ghio AJ, Ghio C, Bassett M. Exercise-induced pulmonary hemorrhage after running a marathon. Lung 184: 331-333, 2006. 4. Frymoyer PA, Anderson Hr GH, Blair DC. Hemoptysis as a presenting symptom of pheochromocytoma. J Clin Hypertens 2: 6567, 1986. 5. Yoshida T, Ishihara H. Pheochromocytoma presenting as massive hemoptysis and acute respiratory failure. Am J Emerg Med 27: 626.e3-626.e4, 2009. 6. Kimura Y, Ozawa H, Igarashi M, et al. A pheochromocytoma causing limited coagulopathy with hemoptysis. Tokai J Exp Clin Med 30: 35-39, 2005. 7. Bourvis N, Fartoukh M, Christin-Maitre S, François T, Parrot A, Mayaud C. Intra-alveolar hemorrhage revealing pheochromocytoma. Rev Pneumol Clin 62: 43-48, 2006 (in French, Abstract in English). 8. Werbel SS, Ober KP. Pheochromocytoma. Update on diagnosis, localization, and management. Med Clin North Am 79: 131-153, 1995. 9. Rosas AL, Kasperlik-Zaluska AA, Papierska L, Bass BL, Pacak K, Eisenhofer G. Pheochromocytoma crisis induced by glucocorticoids: a report of four cases and review of the literature. Eur J Endocrinol 158: 423-429, 2008. 10. Jang SY, Yang DH, Lee SH, et al. Recurrent catecholamineinduced cardiomyopathy in a patient with a pheochromocytoma. Korean Circ J 39: 254-257, 2009. 11. Sukor N, Saidin R, Kamaruddin NA. Epinephrine-secreting pheochromocytoma in a normotensive woman with adrenal incidentaloma. South Med J 100: 73-74, 2007. 12. Wu XM, Chen JJ, Wu CK, Lin LY, Tseng CD. Pheochromocytoma presenting as acute myocarditis with cardiogenic shock in two cases. Intern Med 47: 2151-2155, 2008. 13. Harvey RM, Enson Y, Ferrer MI. A reconsideration of the origins of pulmonary hypertension. Chest 59: 82-94, 1971. 14. Zavorsky GS, Milne EN, Lavorini F, et al. Interstitial lung edema triggered by marathon running. Respir Physiol Neurobiol 190: 137-141, 2014. 15. West JB, Tsukimoto K, Mathieu-Costello O, Prediletto R. Stress failure in pulmonary capillaries. J Applied Physiol 70: 1731-1742, 1991. 16. Kurita A, Takase B, Ishizuka T. Disaster and cardiac disease. Anadolu Kardiyol Derg 1: 101-106, 2001. 17. Young WF Jr. Pheochromocytoma: 1926-1993. Trends in Endocrinol Metab 4: 122-127, 1993.
Ⓒ 2015 The Japanese Society of Internal Medicine http://www.naika.or.jp/imonline/index.html
489
CASE REPORT
□
Paraganglioma-induced Alveolar Hemorrhage Yosuke Makuuchi 1, Mikio Wada 1, Atsushi Kawashima 1, Yu Kataoka 1, Masahito Miyahara 2, Masatomi Ikusaka 2 and Keizo Kagawa 1
Abstract A 21-year-old man twice developed sudden dyspnea during running examinations for promotion. Chest computed tomography (CT) revealed lobular ground-glass opacity and centrilobular shadows bilaterally. The bronchoscopy findings were consistent with alveolar hemorrhage, and echocardiography showed severe hypokinesia a few hours later. A mass was subsequently identified along the abdominal aorta on enhanced CT and iodine-131 metaiodobenzylguanidine scintigraphy. Catecholamine oversecretion, which was later confirmed, may have increased the pulmonary vein pressure, thus resulting in the development of an alveolar hemorrhage, and damaged the cardiac muscles as manifested by hypokinesia. Since the patient had not previously developed alveolar hemorrhage during usual exercise, emotional stress superimposed on the physical activity may have triggered the paraganglioma to secrete excessive catecholamines, thus resulting in the observed symptoms. Key words: alveolar hemorrhage, paraganglioma, catecholamine oversecretion (Intern Med 54: 487-489, 2015) (DOI: 10.2169/internalmedicine.54.2304)
Introduction Diffuse alveolar hemorrhage is a life-threatening syndrome that may cause respiratory failure. Histologically, alveolar hemorrhage can be classified into three types: 1) pulmonary capillaritis, 2) diffuse alveolar damage, including that associated with connective tissue disease, vasculitis, infection and drug intoxication and 3) bland pulmonary hemorrhage without inflammation (1). There are only a few reports of the onset of alveolar hemorrhage following exercise (2, 3) or induced by pheochromocytoma (4-7). However, the mechanisms underlying the development of alveolar hemorrhage remain unclear. We herein report a case of exercise-induced alveolar hemorrhage resulting from excessive emotional stress, which led to catecholamine oversecretion from a paraganglioma and the consequent development of symptoms.
Case Report A 21-year-old male self-defense force member visited our emergency room with sudden chest pain and hemoptysis
that occurred during a running examination for a promotion. His blood pressure on arrival was 140/80 mmHg, with a pulse rate of 90/min, respiratory rate of 42/min and oxygen saturation of 84% without oxygen therapy. Coarse crackles were audible bilaterally during breathing. Blood test findings (e.g., coagulation, inflammation and immune reactions) were normal. A chest X-ray showed bilateral infiltrative shadows, and computed tomography (CT) revealed lobular groundglass opacity and centrilobular shadows (Fig. 1). Although the possibility of acute congestive heart failure was considered, an electrocardiogram and transthoracic echocardiography revealed no abnormalities. We therefore suspected alveolar hemorrhage and transferred the patient to a higher level medical institution. Although the bronchoalveolar lavage fluid was bloody, which supported our diagnosis, we were unable to determine the cause of the patient’s symptoms. Several hours after admission, his blood pressure suddenly dropped, and echocardiography demonstrated severe cardiac wall motion abnormalities, including a left ventricular dimension diastolic/systolic of 52 mm/42 mm and ejection fraction of 35%, with the absence of valvular disease. These abnormalities improved the next day, and the patient’s respiratory condition
１
General Internal Medicine, Fukuchiyama City Hospital, Japan and ２Department of General Medicine, Chiba University Hospital, Japan Received for publication December 12, 2013; Accepted for publication July 13, 2014 Correspondence to Dr. Mikio Wada, [email protected]
487
Intern Med 54: 487-489, 2015
DOI: 10.2169/internalmedicine.54.2304
Figure 1. Image showing bilateral lobular ground-glass opacity and centrilobular shadows.
Figure 3. Image showing an intense uptake on iodine-131 MIBG scintigraphy.
recovered within a few days. He was discharged on day 5 of hospitalization. Despite concerns that the alveolar hemorrhage may recur with exercise, he continued training uneventfully. Five months after discharge, the patient was brought to our emergency room with dyspnea that had presented during another running examination for a promotion. Unlike the first visit, no hemoptysis was observed. His blood pressure was 101/45 mmHg, with a pulse rate of 65/min and his oxygen saturation 100% with 12 L of oxygen. The results of blood tests were again normal. The patient’s breath sounds, chest X-ray and CT findings were similar to those noted on the first visit. Echocardiogram revealed slight mitral regurgitation. These imaging findings and the patient’s medical history led us to suspect recurrence of alveolar hemorrhage. His blood pressure subsequently dropped temporarily after admission; however, he recovered within a few days and was discharged before receiving a final diagnosis. We conferred with other institutions regarding the cause
Figure 2. Image showing a mass along the abdominal aorta (white arrowheads).
of the alveolar hemorrhage in this case. Nevertheless, no differential diagnoses other than acute heart failure without valvular disease were made. Enhanced CT disclosed a mass in the abdominal aorta (Fig. 2). We therefore considered the possibility of the abrupt onset of left heart failure due to catecholamine oversecretion, and consequently confirmed an intense uptake in the mass on iodine-131 metaiodobenzylguanidine (MIBG) scintigraphy (Fig. 3). Two months after the second attack, the oversecretion of catecholamines, except for epinephrine, was confirmed on a 24-hour urine test: epinephrine, 0.008 mg/day (normal range: 0.003-0.04 mg/ day); norepinephrine, 1.75 mg/day (normal range: 0.0310.160 mg/day); and dopamine, 1.26 mg/day (normal range: 0.280-1.10 mg/day). During hospitalization for these tests, the patient exhibited no symptoms and was confirmed to not have hypertension or diabetes. The final diagnosis was a symptomatic paraganglioma; After we told the diagnosis of “paraganglioma” to the patient, it came to our attention that his father was operated on for paraganglioma seven years ago as his family medical history. The current patient’s paraganglioma was surgically removed, and his condition has since remained satisfactory.
Discussion The present case relates to bland pulmonary hemorrhage with a hemodynamic cause resulting from paraganglioma. Alveolar hemorrhage may be triggered by infectious and/or connective tissue diseases, as well as other causes. However, the possibility of an infectious or connective tissue disease was excluded in the present case based on the patient’s test results. A diagnosis of valvular disease was also excluded, given the results of echocardiography performed after the patient’s symptoms improved. Not all patients with pheochromocytoma, including our patient, exhibit continuous hypertension (8-11). Excessive catecholamine secretion can induce sudden blood pressure elevation, which in turn can lead to temporal left ventricular
488
Intern Med 54: 487-489, 2015
DOI: 10.2169/internalmedicine.54.2304
wall motion deficiency (5, 9, 10, 12). The present patient displayed transient cardiac wall motion abnormalities a few hours after the onset of symptoms. Hard exercise and sudden blood pressure elevation have the potential to increase the pulmonary vein pressure and pulmonary wedge pressure (13, 14). In rabbit models, an increased capillary pressure has been shown to induce alveolar hemorrhage (15). Therefore, the combination of excessive catecholamine secretion and exercise may trigger the development of lung edema. Emotional stress has also been reported to increase catecholamine secretion (16). Catecholamine-producing tumors, such as pheochromocytomas, secrete excessive amounts of catecholamines in response to stress resulting from exercise and/or emotional excitation (17). The present patient’s symptoms did not develop during routine selfdefense force training, but rather occurred during two separate examinations for promotion, suggesting that extreme emotional stress may have played a role in the pathogenesis in this case. Indeed, the patient did not have an underlying heart disease, although he suffered from transient cardiac insufficiency during both examinations. The above observations suggest the presence of catecholamine oversecretion due to excessive emotional stress superimposed on heavy exercise, which subsequently induced an abrupt increase in the pulmonary venous pressure associated with alveolar hemorrhage in this patient with paraganglioma. The authors state that they have no Conflict of Interest (COI).
References 1. Lara AR, Schwarz MI. Diffuse alveolar hemorrhage. Chest 137: 1164-1171, 2010. 2. Weiler-Ravell D, Shupak A, Goldenberg I, et al. Pulmonary oedema and haemoptysis induced by strenuous swimming. BMJ
311: 361-362, 1995. 3. Ghio AJ, Ghio C, Bassett M. Exercise-induced pulmonary hemorrhage after running a marathon. Lung 184: 331-333, 2006. 4. Frymoyer PA, Anderson Hr GH, Blair DC. Hemoptysis as a presenting symptom of pheochromocytoma. J Clin Hypertens 2: 6567, 1986. 5. Yoshida T, Ishihara H. Pheochromocytoma presenting as massive hemoptysis and acute respiratory failure. Am J Emerg Med 27: 626.e3-626.e4, 2009. 6. Kimura Y, Ozawa H, Igarashi M, et al. A pheochromocytoma causing limited coagulopathy with hemoptysis. Tokai J Exp Clin Med 30: 35-39, 2005. 7. Bourvis N, Fartoukh M, Christin-Maitre S, François T, Parrot A, Mayaud C. Intra-alveolar hemorrhage revealing pheochromocytoma. Rev Pneumol Clin 62: 43-48, 2006 (in French, Abstract in English). 8. Werbel SS, Ober KP. Pheochromocytoma. Update on diagnosis, localization, and management. Med Clin North Am 79: 131-153, 1995. 9. Rosas AL, Kasperlik-Zaluska AA, Papierska L, Bass BL, Pacak K, Eisenhofer G. Pheochromocytoma crisis induced by glucocorticoids: a report of four cases and review of the literature. Eur J Endocrinol 158: 423-429, 2008. 10. Jang SY, Yang DH, Lee SH, et al. Recurrent catecholamineinduced cardiomyopathy in a patient with a pheochromocytoma. Korean Circ J 39: 254-257, 2009. 11. Sukor N, Saidin R, Kamaruddin NA. Epinephrine-secreting pheochromocytoma in a normotensive woman with adrenal incidentaloma. South Med J 100: 73-74, 2007. 12. Wu XM, Chen JJ, Wu CK, Lin LY, Tseng CD. Pheochromocytoma presenting as acute myocarditis with cardiogenic shock in two cases. Intern Med 47: 2151-2155, 2008. 13. Harvey RM, Enson Y, Ferrer MI. A reconsideration of the origins of pulmonary hypertension. Chest 59: 82-94, 1971. 14. Zavorsky GS, Milne EN, Lavorini F, et al. Interstitial lung edema triggered by marathon running. Respir Physiol Neurobiol 190: 137-141, 2014. 15. West JB, Tsukimoto K, Mathieu-Costello O, Prediletto R. Stress failure in pulmonary capillaries. J Applied Physiol 70: 1731-1742, 1991. 16. Kurita A, Takase B, Ishizuka T. Disaster and cardiac disease. Anadolu Kardiyol Derg 1: 101-106, 2001. 17. Young WF Jr. Pheochromocytoma: 1926-1993. Trends in Endocrinol Metab 4: 122-127, 1993.
Ⓒ 2015 The Japanese Society of Internal Medicine http://www.naika.or.jp/imonline/index.html
489
![[Alveolar hemorrhage].](/assets/img/hold.png)
