미만성폐포출혈로발현한갈색세포종 1 예 울산대학교의과대학강릉아산병원 1 영상의학교실, 2 내과학교실류대식 1, 정형주 2, 김미혜 2, 정복현 2 A Case of Pheochromocytoma that Initially Presented as Diffuse Alveolar Hemorrhage Dae Sick Ryu, M.D. 1, Hyoung Chu Joung, M.D. 2, Mi Hye Kim, M.D. 2, Bock Hyun Jung, M.D. 2 Departments of 1 Radiology, 2 Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea A pheochromocytoma is a neuroectodermal tumor that originates from the chromaffin cells of the sympathetic system. Typical symptoms or signs are periodic attacks of paroxysmal hypertension, spell, palpitation, headache and sweating. However, the clinical presentation is quite variable. Therefore, an atypical clinical presentation sometimes makes a diagnosis difficult. Hemoptysis as a presenting symptom is very rare in pheochromocytoma. We recently experienced a patient with diffuse alveolar hemorrhage due to pheochromocytoma. A chest PA showed diffuse consolidation and ground glass opacities in both lungs. A chest CT showed diffuse consolidation and ground glass opacities in the central, middle and lower portion predominance of the lungs, sparing the costophrenic angles and apices of the lungs. In Korea, a case of pheochromocytoma that presented initially as massive hemoptysis due to diffuse alveolar hemorrhage has not been previously reported. We report the case with a review of the literature. (Tuberc Respir Dis 2008;64:52-56) Key Words: Hemoptysis, Pheochromocytoma, Computed tomography 서 갈색세포종은신경외배엽에서분화된크롬친화성세포에서발생하는종양으로여러가지카테콜라민을분비함으로써그증세를일으킨다. 전형적인증상으로주기적인발작성고혈압, 두통, 심계항진, 발한등을보이는데이외에도합병증으로인한뇌혈관질환, 심근경색, 임신중독증등으로인한증상을나타내는경우도있다. 드물게객혈, 전신발작등비전형적인증세를보이는경우에는진단에어려움을겪는다. 이종양은드문질환이나치료가될수있는이차성고혈압의한원인으로정확한진단과치료가이루어지지않으면발작적인고혈압의발생으로신경학적또는심혈관계합병증으로치명적인결과를초래할수 Address for correspondence: Bock Hyun Jung, M.D. Department of Internal Medicine, Gangneung Asan Hospital, 415, Bangdong-ri, Sacheon-myeon, Gangneung 210-711, Korea Phone: 82-33-610-3139, Fax: 82-33-641-8130 E-mail: jbh@gnah.co.kr Received: Dec. 11, 2007 Accepted: Jan. 18, 2008 론 있다. 갈색세포종을포함한크롬친화세포증에의한객혈은매우드물며, 지금까지문헌에약 6예만이보고되었다 1-6. 저자들은미만성폐포출혈양상의대량객혈을주소로내원한환자에서흉부전산화단층촬영및생화학적검사로갈색세포종으로확진된 1예를경험하여고해상전산단층촬영 (HRCT) 의소견을포함하여문헌고찰과함께보고하는바이다. 증례환자 : 김, 45세여자주소 : 내원하루전부터시작된객혈현병력 : 내원 20년전부터개인병원에서고혈압진단을받고항고혈압제를복용중이었으며일년전부터간헐적인호흡곤란이있었고한달전에기침과함께약 20 cc의객혈을한적이있었으며, 내원하루전부터 500 cc 이상의객혈을보여본원응급실을통해입원하였다. 과거력 : 20년전에고혈압을진단받았고, 15년전에충수절제술을받았다. 52
Tuberculosis and Respiratory Diseases Vol. 64. No. 1, Jan. 2008 Figure 1. (A) Chest PA shows ground glass opacities and consolidation (short arrow) in the central, mid/lower lung predominance, sparing costophernic angles and apices (long arrow) in the both lungs with hypertensive heart configuration. (B) Follow up Chest PA show complete disappearance of the infiltration at both lung field. 이학적소견 : 내원시급성병색을보였고, 혈압은 230/150 mmhg, 호흡수 28회 / 분, 체온 36.4 o C, 맥박은분당 95회였고규칙적이었다. 의식은명료하였으나경미한호흡곤란, 기침시흉통과소량의황색객담이있었다. 흉곽의변형은없었고대칭적인팽창을보였고양측하폐야에서거친호흡음과수포음이들렸다. 약간의구토증상을호소하였으나복부의이학적소견은정상이었다. 사지의부종은없었고신경학적검사에서이상소견은없었다. 검사실소견 : 말초혈액검사에서백혈구수 11,300/mm 3, 혈색소 13.1 g/dl, 혈소판수는 286,000/mm 3 이었고, 대기중시행한동맥혈가스분석상 ph 7.42, PaCO2 35.8 mmhg, PaO2 66.8 mmhg, 산소포화도 92.9% 였다. 혈청생화학검사는 lactate dehydrogenase (LDH) 694 IU/L으로약간증가된소견이외의다른특이사항이없었으며, 혈액응고검사에서 prothrombin time 97.6% (1.02 INR), activated partial thromboplastin time 28.4초로정상이었다. 혈청항핵항체, 류마티스인자, 항중성구세포질항체 (ANCA) 및항인지질항체 (antiphospholipid antibody) 검사도모두음성이었다. 방사선검사소견 : 내원당시흉부방사선촬영상고혈압성심장형태와함께양폐의중하엽의폐문주위로간유리음영과경결성병변이보였고폐첨과늑골횡격막각에는병변이침범되지않는특징적인소견이관찰되었다 (Figure 1A). 응급심초음파검사상고혈압성심비대이외 Figure 2. HRCT shows multifocal patchy consolidation (arrow head) with surrounding ground glass opacities in the central distribution of the both upper lobes and lower lobes. 심부전소견은없었다. 고해상전산단층촬영에서양폐의중심성부위에다발성의간유리음영과경결이관찰되었다 (Figure 2). 조영증강전산단층촬영에서좌측부신에약 6.5 7 cm크기의석회화와괴사조직을포함하는원형의종괴가보였다 (Figure 3). 이종괴는중등도조영증강을보이는과혈관성병변으로좌측신장을후방으로밀고있었다. 53
DS Ryu et al: Pheochromocytoma initially presented as diffuse alveolar hemorrhage Figure 3. Contrast-enhanced CT shows 6.5 7 cm sized round mass (arrow) with calcification and necrosis in the left adrenal gland, showing with moderate enhancement displacing left kidney posteriorly. 핵의학소견 : Iodine-131 metaiodobenzylguanidine (MIBG) scintigraph 에서좌측부신의 6.5 cm 크기의영역에섭취율이증가하여갈색세포종에합당한소견을보였다 (Figure 4). 치료및경과 : 내원시시행한흉부전산화촬영상부신종양과악성고혈압으로갈색세포종의증하에알파및베타아드레날린차단제를포함한항고혈압제를사용하여적극적으로혈압을조절하고대증요법으로치료후다량의객혈소견은호전되었고일주일후촬영한단순흉부사진에서내원당시보였던간유리음영및경결성병변은완전히사라졌다 (Figure 1B). 입원중시행한 24시간소변내에피네프린 143μg/day, 노르에피네프린 2,266μg/day, 메타네프린 6,545μg/day 으로모두증가되어있었고, MIBG scan에서좌측부신동위원소습취율의증가소견을보여갈색세포종확진하에수술적치료를권유하였으나환자가수술적치료를강력히거부하여외래에서항고혈압제를투약하기로하고퇴원하였다. 이후객혈의재발소견은없었고 1년후시행한전산단층촬영과핵의학검사에서종괴의크기는변함이없는상태로현재외래에서혈압조절과함께추적관찰중이다. 고 미만성폐포출혈에의한대량객혈의원인은매우다양하다. 대부분은종양과관련이없는굿파스처증후군 (Goodpasture s syndrome), 항중성구세포질항체와연관 찰 Figure 4. Iodine-131 metaiodobenzylguanidine (MIBG) scintigraphy shows increased uptake (arrow) in the left adrenal gland area. 된소혈관염, 교원성혈관질환, 특발성폐혈철소침착증, 응고장애및다양한약물과독소로인하여발생할수있다 7. 그러나종양의직접적인폐전이로인한출혈이외에종양에의해미만성폐출혈이발생하는경우는매우드물며신경외배엽종양중심한고혈압으로인한폐정맥압의갑작스러운상승으로폐출혈을일으키는갈색세포종이대표적이다 1-6. 갈색세포종은크롬친화성세포로부터카테콜라민을분비하는종양이다. 치료하지않은크롬친화세포종은심부정맥과악성고혈압으로인해사망을초래할수있다. 90% 이상은부신에서발생하고갈색세포종이라불리며, 복강내에서 98% 이상발생한다. 부신이외에서발생하는크롬친화세포종은대동맥복측면에산재해있는교감신경계방절의크롬친화세포에서발생하며부신경절종 (paraganglioma) 로불린다. 갈색세포종의진단은합당한생화학검사소견, 임상소견과함께영상소견으로할수있다. 임상발현은치료에반응하지않는발작성고혈압, 심계항진, 두통과발한등의증상을보인다. 생화학검사는혈청메타네프린과 24시간요카테콜라민수치가정상의두배이상의증가를보인다. 조직검사는갑작스러운고혈압으로사망을초래할수있으므로피해야한다. 갈색세포종은고형의과혈관성종괴로서조영증강전산단층촬영에서조영증강이매우잘되는고형종괴지만내부에지방, 석회화와괴사에의해다양한조영증강형태를보일수있다. 핵의학검사인 I-131 혹은 I-123 MIBG scintigraphy는 100% 특이도를보여갈색세포종을확진할수있다 8. 54
Tuberculosis and Respiratory Diseases Vol. 64. No. 1, Jan. 2008 입원당시환자는임상소견, 생화학적검사및영상소견으로갈색세포종으로진단하였다. 환자는수술적치료를거부하여병리소견을얻지못하였으나생화학검사및핵의학검사에서갈색세포종으로진단하는데문제는없었으며영상소견및추적검사에서더이상의객혈은없었고종양의크기도변화가없었다. 갈색세포종환자에서객혈은주로고혈압의발작동안에발생한다. 갑작스러운혈압상승을일으키는카테콜라민분비는폐부종과폐출혈을일으킬수있다. 갈색세포종에서객혈이발생하는기전으로는증가된 thrombin-antithrombin III complex (TAT), prothrombin fragment factor 1 과 2에의해응고연속단계 (cascade) 의활성화가출혈을일으킬수있으며, 증가된혈청 von Willebrand factor (vwf) 에의한혈관내피세포및혈소판자극에의해서도출혈이올수있다 2. 갈색세포종을포함한크롬친화세포종에의한객혈은매우드물어국내에서도객혈을동반한갈색세포종에관한증례보고가 Jung 등 6 이보고한바있으나본증례와달리내원시심한심부전에동반된 10 20 cc 정도의소량의객혈이치료도중에발생한경우로서본증례는응급실내원시고혈압이동반되었으나심부전의소견없이미만성폐포출혈양상의대량객혈을주소로내원한경우로객혈의발생양상과발생기전이서로다를것으로사료된다. 급성폐포출혈의영상은그원인에상관없이거의동일하며폐경결성 (airspace consolidation) 양상을보인다 7. 특이하게특발성폐혈철소침착증인경우는장기간에걸친반복성출혈로인해간질성섬유화를초래한다. 작은크기의경결은폐소포성크기에서부터공기기관지음영을보일정도의광범위경결을보인다. 폐경결은광범위하게산재될수도있으나, 특징적으로폐중하엽부위의폐문중심성분포를보이며폐첨과늑횡격막각의부위는보통침범하지않는다. 폐경결이사라지는속도는폐부종과폐렴의호전되는속도의중간정도인 2 3일내에사라진다. 급성기에는전산단층촬영상경결과간유리음영을보이고수일후에는혈철소를잡아먹은대식세포가간질에침착되므로소엽간중격이두꺼워지고조각보이불모양 (crazy-paving appearance) 을보일수있다 9-12. 저자의예는급성기에영상을얻어소엽간중격이두꺼워지거나조각보이불모양은관찰되지않았다. 전산단층영상에서폐포출혈, 폐염및 ARDS 을포함한투과성폐부종의감별진단은쉽지않으나, 갈색세포종에의한고혈압성폐포출혈에서는병변부위가특징적으로 폐문부위중하엽에호발하고폐첨과늑횡격막각을침범하지않는소견으로전산단층촬영이감별에도움이될수있다. 결론적으로저자들은갈색세포종에의한객혈을경험하였고전산단층촬영영상에서폐문주위중하엽에국한된간유리음영과경결을보이는병변의위치와모양으로갈색세포종에의한미만성폐포출혈을진단하는데도움을받았으며, 드물지만갈색세포종을포함한신경외배엽종양도미만성폐포출혈을일으키는질환의감별에고려되어야할것으로사료된다. 참고문헌 1. Frymoyer PA, Anderson GH Jr, Blair DC. Hemoptysis as a presenting symptom of pheochromocytoma. J Clin Hypertens 1986;2:65-7. 2. Kimura Y, Ozawa H, Igarashi M, Iwamoto T, Nishiya K, Urano T, et al. A pheochromocytoma causing limited coagulopathy with hemoptysis. Tokai J Exp Clin Med 2005;30:35-9. 3. Colas JL. Paroxysmal hypertension with haemoptysis due to a retroperitoneal paraganglioma. East Afr Med J 1965;42:535-40. 4. Iino S, Nagashima N, Akiba H, Ban Ymiyamoto M. Hemoptysis and palpitation (with hypertension): pheochromocytoma. Nippon Rinsho 1975;Spec No:918-9, 1394-5. 5. Bourvis N, Fartoukh M, Christin-Maitre S, Francois T, Parrot A, Mayaud C. Intra-alveolar hemorrhage revealing pheochromocytoma. Rev Pneumol Clin 2006;62: 43-8. 6. Jung YS, Kim JG, Song SK, Kwon SK, Choi YS, Jang TW, et al. A case of pheochromocytoma accompanied with hemoptysis. Kosin Med J 2000;15:103-7. 7. Amstrong P, Wilson AG, Dee P, Hansell DM. Imaging of disease of the chest. 3rd ed. London: Mosby; 2000. p. 582-6. 8. Blake MA, Kalra MK, Maher MM, Sahani DV, Sweeney AT, Mueller PR, et al. Pheochromocytoma: an imaging chameleon. Radiographics 2004;24:S87-99. 9. Albelda SM, Gefter WB, Epstein DM, Miller WT. Diffuse pulmonary hemorrhage: a review and classification. Radiology 1985;154:289-97. 10. Rossi SE, Erasmus JJ, Volpacchio M, Franquet T, McAdams HP. Crazy-paving pattern at thin-section CT of the lungs: radiologic-pathologic overview. Radiographics 2003;23:1509-19. 55
DS Ryu et al: Pheochromocytoma initially presented as diffuse alveolar hemorrhage 11. Primack SL, Miller RR, Müller NL. Diffuse pulmonary hemorrhage: clinical, pathologic, and imaging features. AJR Am J Roentgenol 1995;164:295-300. 12. Webb WR, Müller NL, Naidich DP. High resolution CT of the lung. 3rd ed. Philadelphia: Lippincott Willams & Wilkins; 2001. p. 408-9. 56