Acute upper extremity arterial thrombosis and stroke in an unresected pheochromocytoma
2013; Elsevier BV; Volume: 58; Issue: 4 Linguagem: Inglês
10.1016/j.jvs.2012.12.058
ISSN1097-6809
AutoresSameer Kaiser, John Chronakos, Alan M. Dietzek,
Tópico(s)Hormonal Regulation and Hypertension
ResumoPheochromocytoma is a rare cause of hypertension in the general population. Only isolated reports show an association with acute obstructive arterial thrombosis. A 50-year-old chronically noncompliant woman with a known unresected pheochromocytoma presented to the emergency department with ataxia. Imaging confirmed a right-sided ischemic stroke. During her hospital stay, the patient developed signs consistent with acute right upper extremity ischemia resulting from occlusion in the distal right subclavian, axillary, and proximal brachial arteries. Emergent open thrombectomy was successfully performed. In patients with an unresected pheochromocytoma, one must consider acute arterial thrombosis as a rare but potentially limb-threatening and even life-threatening complication. Pheochromocytoma is a rare cause of hypertension in the general population. Only isolated reports show an association with acute obstructive arterial thrombosis. A 50-year-old chronically noncompliant woman with a known unresected pheochromocytoma presented to the emergency department with ataxia. Imaging confirmed a right-sided ischemic stroke. During her hospital stay, the patient developed signs consistent with acute right upper extremity ischemia resulting from occlusion in the distal right subclavian, axillary, and proximal brachial arteries. Emergent open thrombectomy was successfully performed. In patients with an unresected pheochromocytoma, one must consider acute arterial thrombosis as a rare but potentially limb-threatening and even life-threatening complication. Pheochromocytoma is a rare cause of hypertension in the general population, representing <0.2% of cases.1Pacak K. Linehan W.M. Eisenhofer G. Walther M.M. Goldstein D.S. Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma.Ann Intern Med. 2001; 134: 315-329Crossref PubMed Scopus (484) Google Scholar The classic triad presentation consists of headaches, diaphoresis, and palpitations. Although most do not present with this triad, paroxysmal hypertension is found in ∼50% of patients. Major complications, including papilledema, hypertensive emergency, and cardiomyopathy, are the result of elevated blood pressure and catecholamine excess. Numerous published reports have documented the association of pheochromocytoma with the development of systemic and intracardiac thrombi.2Zhou W. Ding S.F. Concurrent pheochromocytoma, ventricular tachycardia, left ventricular thrombus, and systemic embolization.Intern Med. 2009; 48: 1015-1019Crossref PubMed Scopus (19) Google Scholar, 3Hou R. Leathersich A.M. Ruud B.T. Pheochromocytoma presenting with arterial and intracardiac thrombus in a 47-year-old woman: a case report.J Med Case Rep. 2011; 5: 310Crossref PubMed Scopus (11) Google Scholar, 4Brauchlin A.E. Rudiger A. Bächli E.B. Schmid C. Maggiorini M. Portal vein thrombosis and liver failure in a patient with pheochromocytoma crisis.Am J Emerg Med. 2009; 27: 630.e3-630.e5Abstract Full Text Full Text PDF Scopus (8) Google Scholar, 5Mrdovic I. Perunicic J. Asanin M. Matic M. Vasiljevic Z. Ostojic M. Transient left ventricular apical ballooning complicated by a mural thrombus and outflow tract obstruction in a patient with pheochromocytoma.Tex Heart Inst J. 2008; 35: 480-482PubMed Google Scholar, 6Kota S.K. Jammula S. Meher L.K. Modi K.D. Pheochromocytoma with inferior vena cava thrombosis: An unusual presentation.J Cardiovasc Dis Res. 2012; 3: 160-164Abstract Full Text PDF PubMed Scopus (4) Google Scholar, 7Dagartzikas M.I. Sprague K. Carter G. Tobias J.D. Cerebrovascular event, dilated cardiomyopathy, and pheochromocytoma.Pediatr Emerg Care. 2002; 18: 33-35Crossref PubMed Scopus (31) Google Scholar, 8Stevenson S. Ramani V. Nasim A. Extra-adrenal pheochromocytoma: an unusual case of deep venous thrombosis.J Vasc Surgery. 2005; 42: 570-572Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 9Heindel S.W. Maslow A.D. Steriti J. Mashikian J.S. A patient with intracardiac masses and an undiagnosed pheochromocytoma.J Cardiothorac Vasc Anesth. 2002; 16: 338-343Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar, 10Stella P. Bignotti G. Zerbi S. Ciurlino D. Landoni C. Fazio F. et al.Concurrent pheochromocytoma, diabetes insipidus and cerebral venous thrombosis—a possible unique pathophysiological mechanism.Nephrol Dial Transplant. 2000; 15: 717-718Crossref PubMed Scopus (7) Google Scholar, 11Raghavan R. Ince P.G. Walls T.J. Gholkar A. Dark J.H. Foster J.B. Malignant cerebrovascular thromboembolization by phaeochromocytoma.Clin Neuropathol. 1995; 14: 69-71PubMed Google Scholar, 12Ku C.F. Lo C.Y. Chan W.F. Chiu S.W. Fan S.T. Lam K.S.L. Resection of phaeochromocytoma extending into the right atrium in a patient with multiple endocrine neoplasia type 2A.Hong Kong Med J. 2005; 11: 59-62PubMed Google Scholar, 13Lucon A.M. Machado M.C. Pereira M.A. Mendonca B.B. Praxedes J.N. Arap S. Surgery for adrenal tumours with thrombus in the supra-diaphragmatic infra-atrial inferior vena cava, with no cardiopulmonary bypass.BJU Int. 2004; 94: 70-73Crossref PubMed Scopus (11) Google Scholar, 14Lucon A.M. Falci Jr., R. Praxedes J.N. Machado M.C. Saldanha L.B. Machado M.M. et al.Multicentric pheochromocytoma and involvement of the inferior vena cava.Sao Paulo Med J. 2001; 119: 86-88Crossref PubMed Scopus (7) Google Scholar, 15Dural C. Bilge O. Toker A. Erbil Y. Salmaslioglu A. Ozbey N. et al.Malignant phaeochromocytoma with cavoatrial extension: transcaval removal of tumor without cardiopulmonary bypass a case report.Minerva Chir. 2010; 65: 485-488PubMed Google Scholar, 16Novick A.C. Kaye M.C. Cosgrove D.M. Angermeier K. Pontes J.E. Montie J.E. et al.Experience with cardiopulmonary bypass and deep hypothermic circulatory arrest in the management of retroperitoneal tumors with large vena caval thrombi.Ann Surg. 1990; 212: 472-476Crossref PubMed Scopus (201) Google Scholar, 17Pishdad G.R. Ventricular thrombosis in Sipple's syndrome.South Med J. 2000; 93: 1093-1095PubMed Google Scholar, 18Robert B. Chivot C. Degremont R. Trouillet N. Lafaye-Boucher N. Gondry-Jouet C. et al.Thrombosis of the superior mesenteric vein revealing an ectopic pheochromocytoma of the organ of Zuckerkandl.Diagn Interv Imaging. 2012; 93: 625-628Crossref PubMed Scopus (3) Google Scholar, 19Rötker J. Oberpennig F. Scheld H.H. Hertle L. Knichwitz G. Hammel D. Pheochromocytomas with extension into central vascular structures.Ann Thorac Surg. 1996; 61: 222-224Abstract Full Text PDF PubMed Scopus (16) Google Scholar, 20Shigemura K. Tanaka K. Arakawa S. Hara I. Kawabata G. Fujisawa M. Malignant pheochromocytoma with IVC thrombus.Int Urol Nephrol. 2007; 39: 103-106Crossref PubMed Scopus (10) Google Scholar, 21Osman Y. Haraz A. El-Mekresh M. Gomha A.M. El-Ghar M.A. Eraky I. Adrenal tumors with venous thrombosis: a single-institution experience.Urol Int. 2011; 87: 182-185Crossref PubMed Scopus (11) Google Scholar, 22Wiyono S.A. Vletter W.B. Soliman O.I. ten Cate F.J. Geleijnse M.L. Thrombus in a normal left ventricle: a cardiac manifestation of pheochromocytoma.Echocardiography. 2010; 27: 195-197Crossref PubMed Scopus (8) Google Scholar, 23Yebra Yebra M. Martín Asenjo R. Arrue I. Paz Yepes M. Bastante Valiente M.T. Prieto S. Acute myocardial ischemia and ventricular thrombus associated with pheochromocytoma.Rev Esp Cardiol. 2005; 58: 598-600Crossref PubMed Scopus (11) Google Scholar, 24Dunn C.W. Snyder W.H. Ring W.S. Latson T.W. Pheochromocytoma with extension into the inferior vena cava: a case report.Surgery. 1992; 111: 472-474PubMed Google Scholar, 25Shulkin B.L. Shapiro B. Sisson J.C. Pheochromocytoma, polycythemia, and venous thrombosis.Am J Med. 1987; 83: 773-776Abstract Full Text PDF PubMed Scopus (22) Google Scholar When present, the intracardiac thrombus serves as a nidus for emboli to the brain, kidneys, and distal extremities.2Zhou W. Ding S.F. Concurrent pheochromocytoma, ventricular tachycardia, left ventricular thrombus, and systemic embolization.Intern Med. 2009; 48: 1015-1019Crossref PubMed Scopus (19) Google Scholar, 3Hou R. Leathersich A.M. Ruud B.T. Pheochromocytoma presenting with arterial and intracardiac thrombus in a 47-year-old woman: a case report.J Med Case Rep. 2011; 5: 310Crossref PubMed Scopus (11) Google Scholar, 7Dagartzikas M.I. Sprague K. Carter G. Tobias J.D. Cerebrovascular event, dilated cardiomyopathy, and pheochromocytoma.Pediatr Emerg Care. 2002; 18: 33-35Crossref PubMed Scopus (31) Google Scholar, 9Heindel S.W. Maslow A.D. Steriti J. Mashikian J.S. A patient with intracardiac masses and an undiagnosed pheochromocytoma.J Cardiothorac Vasc Anesth. 2002; 16: 338-343Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar, 23Yebra Yebra M. Martín Asenjo R. Arrue I. Paz Yepes M. Bastante Valiente M.T. Prieto S. Acute myocardial ischemia and ventricular thrombus associated with pheochromocytoma.Rev Esp Cardiol. 2005; 58: 598-600Crossref PubMed Scopus (11) Google Scholar Of the 28 patients reported in the literature, a left ventricle thrombus was identified in only eight (Table). Inferior vena cava (IVC) thrombi were present in 13 patients, with some thrombi extending to the level of the right atrium. Of note, the IVC thrombus in 11 of these patients was due to direct tumor spread. Alternatively, only one case report has documented an association between pheochromocytoma and an isolated acute arterial thrombosis.11Raghavan R. Ince P.G. Walls T.J. Gholkar A. Dark J.H. Foster J.B. Malignant cerebrovascular thromboembolization by phaeochromocytoma.Clin Neuropathol. 1995; 14: 69-71PubMed Google Scholar We present the case of a 50-year-old woman with pheochromocytoma who developed an acute occlusive arterial thrombosis of the upper extremity.TableLiterature review of thrombotic complications of pheochromocytoma in English language journalsStudyPts, No.Age, yearsSexSize, cmThrombus locationEmboli locationTime to thrombosisHormone secretion?BP controlled?aAdequately controlled BP defined as ≤140/80 mm Hg.Anticoagulation managementCurrent150F7.8Right subclavian to radial arteryNone6 monthsYesYesIV heparinZhou2Zhou W. Ding S.F. Concurrent pheochromocytoma, ventricular tachycardia, left ventricular thrombus, and systemic embolization.Intern Med. 2009; 48: 1015-1019Crossref PubMed Scopus (19) Google Scholar143F4.0Left ventricleBilateral femoral and renal arteriesFODUYesWarfarin, urokinaseHou3Hou R. Leathersich A.M. Ruud B.T. Pheochromocytoma presenting with arterial and intracardiac thrombus in a 47-year-old woman: a case report.J Med Case Rep. 2011; 5: 310Crossref PubMed Scopus (11) Google Scholar147F8.0Left ventricle, left axillary arteryNoneFODYesYesWarfarin, clopidogrelBrauchlin4Brauchlin A.E. Rudiger A. Bächli E.B. Schmid C. Maggiorini M. Portal vein thrombosis and liver failure in a patient with pheochromocytoma crisis.Am J Emerg Med. 2009; 27: 630.e3-630.e5Abstract Full Text Full Text PDF Scopus (8) Google Scholar151M8.0Portal veinNone4 yearsYesNoIV to unknown oral agentMrdovic5Mrdovic I. Perunicic J. Asanin M. Matic M. Vasiljevic Z. Ostojic M. Transient left ventricular apical ballooning complicated by a mural thrombus and outflow tract obstruction in a patient with pheochromocytoma.Tex Heart Inst J. 2008; 35: 480-482PubMed Google Scholar153FULeft ventricleNoneFODYesUIV heparin, aspirinKota6Kota S.K. Jammula S. Meher L.K. Modi K.D. Pheochromocytoma with inferior vena cava thrombosis: An unusual presentation.J Cardiovasc Dis Res. 2012; 3: 160-164Abstract Full Text PDF PubMed Scopus (4) Google Scholar148M7.6IVC, right atriumNoneFODYesNoIV heparin, warfarinDagartzikas7Dagartzikas M.I. Sprague K. Carter G. Tobias J.D. Cerebrovascular event, dilated cardiomyopathy, and pheochromocytoma.Pediatr Emerg Care. 2002; 18: 33-35Crossref PubMed Scopus (31) Google Scholar113M8.5Left ventricleMultiple cerebral emboliFODYesNoTPAStevenson8Stevenson S. Ramani V. Nasim A. Extra-adrenal pheochromocytoma: an unusual case of deep venous thrombosis.J Vasc Surgery. 2005; 42: 570-572Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar146M9.0Left femoral veinNoneFODYesNoLMWH, warfarinHeindel9Heindel S.W. Maslow A.D. Steriti J. Mashikian J.S. A patient with intracardiac masses and an undiagnosed pheochromocytoma.J Cardiothorac Vasc Anesth. 2002; 16: 338-343Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar149M10Three left ventricle massesRight cerebral and cerebellar arteries, splenic artery, right femoral arteryFODYesNoIV heparin, aspirinStella10Stella P. Bignotti G. Zerbi S. Ciurlino D. Landoni C. Fazio F. et al.Concurrent pheochromocytoma, diabetes insipidus and cerebral venous thrombosis—a possible unique pathophysiological mechanism.Nephrol Dial Transplant. 2000; 15: 717-718Crossref PubMed Scopus (7) Google Scholar138M4-5Cerebral venous thrombosisNoneFODYesUOral agent (U)Raghavan11Raghavan R. Ince P.G. Walls T.J. Gholkar A. Dark J.H. Foster J.B. Malignant cerebrovascular thromboembolization by phaeochromocytoma.Clin Neuropathol. 1995; 14: 69-71PubMed Google Scholar156M10Right innominate and left common carotid arteriesNoneFODUUUKu12Ku C.F. Lo C.Y. Chan W.F. Chiu S.W. Fan S.T. Lam K.S.L. Resection of phaeochromocytoma extending into the right atrium in a patient with multiple endocrine neoplasia type 2A.Hong Kong Med J. 2005; 11: 59-62PubMed Google Scholar121F12IVC, right atriumbRepresents direct tumor extension.NoneFODYesNoNoneLucon13Lucon A.M. Machado M.C. Pereira M.A. Mendonca B.B. Praxedes J.N. Arap S. Surgery for adrenal tumours with thrombus in the supra-diaphragmatic infra-atrial inferior vena cava, with no cardiopulmonary bypass.BJU Int. 2004; 94: 70-73Crossref PubMed Scopus (11) Google Scholar343M10.6IVCbRepresents direct tumor extension.NoneFODUUU46M8IVCbRepresents direct tumor extension.NoneUUU24F5.5IVCbRepresents direct tumor extension.NoneUUULucon14Lucon A.M. Falci Jr., R. Praxedes J.N. Machado M.C. Saldanha L.B. Machado M.M. et al.Multicentric pheochromocytoma and involvement of the inferior vena cava.Sao Paulo Med J. 2001; 119: 86-88Crossref PubMed Scopus (7) Google Scholar143M6.5IVCbRepresents direct tumor extension.NoneFODYesYesNoneDural15Dural C. Bilge O. Toker A. Erbil Y. Salmaslioglu A. Ozbey N. et al.Malignant phaeochromocytoma with cavoatrial extension: transcaval removal of tumor without cardiopulmonary bypass a case report.Minerva Chir. 2010; 65: 485-488PubMed Google Scholar117M10IVC, right atriumbRepresents direct tumor extension.NoneFODYesUNoneNovick16Novick A.C. Kaye M.C. Cosgrove D.M. Angermeier K. Pontes J.E. Montie J.E. et al.Experience with cardiopulmonary bypass and deep hypothermic circulatory arrest in the management of retroperitoneal tumors with large vena caval thrombi.Ann Surg. 1990; 212: 472-476Crossref PubMed Scopus (201) Google Scholar1UUUIVCbRepresents direct tumor extension.NoneUUUUPishdad17Pishdad G.R. Ventricular thrombosis in Sipple's syndrome.South Med J. 2000; 93: 1093-1095PubMed Google Scholar118F8Left ventricleNoneFODYesUURobert18Robert B. Chivot C. Degremont R. Trouillet N. Lafaye-Boucher N. Gondry-Jouet C. et al.Thrombosis of the superior mesenteric vein revealing an ectopic pheochromocytoma of the organ of Zuckerkandl.Diagn Interv Imaging. 2012; 93: 625-628Crossref PubMed Scopus (3) Google Scholar143M7Superior mesenteric veinNoneFODYesUYes, U medRötker19Rötker J. Oberpennig F. Scheld H.H. Hertle L. Knichwitz G. Hammel D. Pheochromocytomas with extension into central vascular structures.Ann Thorac Surg. 1996; 61: 222-224Abstract Full Text PDF PubMed Scopus (16) Google Scholar251M4.3IVCbRepresents direct tumor extension.NoneFODYesUNone58FUIVC, right atriumbRepresents direct tumor extension.None2 yearscAt 2 years after resection of primary tumor, patient developed metastatic disease and venous thrombosis.UUNoneShigemura20Shigemura K. Tanaka K. Arakawa S. Hara I. Kawabata G. Fujisawa M. Malignant pheochromocytoma with IVC thrombus.Int Urol Nephrol. 2007; 39: 103-106Crossref PubMed Scopus (10) Google Scholar161M6IVCbRepresents direct tumor extension.NoneFODYesUNoneOsman21Osman Y. Haraz A. El-Mekresh M. Gomha A.M. El-Ghar M.A. Eraky I. Adrenal tumors with venous thrombosis: a single-institution experience.Urol Int. 2011; 87: 182-185Crossref PubMed Scopus (11) Google Scholar2UMUAdrenal and renal veinNoneUUUUUMUAdrenal and renal veinNoneUUUUWiyono22Wiyono S.A. Vletter W.B. Soliman O.I. ten Cate F.J. Geleijnse M.L. Thrombus in a normal left ventricle: a cardiac manifestation of pheochromocytoma.Echocardiography. 2010; 27: 195-197Crossref PubMed Scopus (8) Google Scholar143MULeft ventricleNoneFODUYesYes, U medYebra Yebra23Yebra Yebra M. Martín Asenjo R. Arrue I. Paz Yepes M. Bastante Valiente M.T. Prieto S. Acute myocardial ischemia and ventricular thrombus associated with pheochromocytoma.Rev Esp Cardiol. 2005; 58: 598-600Crossref PubMed Scopus (11) Google Scholar159M3.5Left ventricleLeft cerebral emboliFODYesNoHeparinDunn24Dunn C.W. Snyder W.H. Ring W.S. Latson T.W. Pheochromocytoma with extension into the inferior vena cava: a case report.Surgery. 1992; 111: 472-474PubMed Google Scholar157M10IVCbRepresents direct tumor extension.NoneFODYesYesNoneShulkin25Shulkin B.L. Shapiro B. Sisson J.C. Pheochromocytoma, polycythemia, and venous thrombosis.Am J Med. 1987; 83: 773-776Abstract Full Text PDF PubMed Scopus (22) Google Scholar132MUIVC, right common femoral and inferior epigastric veinsNone21 yearsdPatient with polycythemia and recurrent metastatic pheochromocytoma (first diagnosed 21 years prior).UYesIV heparin, warfarinBP, Blood pressure; F, female; FOD, found on diagnosis of tumor; IV, intravenous; IVC, inferior vena cava; LMWH, low-molecular-weight heparin; M, male; Pts, patients; tPA, tissue plasminogen activator; U, unknown.a Adequately controlled BP defined as ≤140/80 mm Hg.b Represents direct tumor extension.c At 2 years after resection of primary tumor, patient developed metastatic disease and venous thrombosis.d Patient with polycythemia and recurrent metastatic pheochromocytoma (first diagnosed 21 years prior). Open table in a new tab BP, Blood pressure; F, female; FOD, found on diagnosis of tumor; IV, intravenous; IVC, inferior vena cava; LMWH, low-molecular-weight heparin; M, male; Pts, patients; tPA, tissue plasminogen activator; U, unknown. A 50-year-old woman presented to the emergency department with ataxia. The physical examination found a severely elevated blood pressure (BP) of 200/130 mm Hg and fluctuating weakness in the left upper and lower extremities. She had been diagnosed 6 months earlier with a 7.8-cm pheochromocytoma in the left adrenal gland. At the time of diagnosis, 24-hour urine studies demonstrated elevated metanephrines (55,467 μg) and normetanephrines (19,043 μg). In addition, plasma metanephrines and normetanephrines were elevated at 82nM (normal <0.5nM) and 96nM (normal <0.5nM), respectively. Analysis of a percutaneous biopsy specimen confirmed the diagnosis of pheochromocytoma. The patient left the hospital 4 days earlier, against medical advice, after being admitted for a hypertensive emergency. During the prior admission, she was being kept in the hospital to maintain control of her BP before a planned resection of her tumor. The patient was chronically noncompliant with medical therapy, which resulted in multiple previous admissions for acute hypertensive emergency that delayed a safe resection of the tumor. At the time of this admission, she had not been taking her prescribed antihypertensive medications. Her comorbidities included hypertrophic cardiomyopathy, seizures, and bipolar disorder. Computed tomography (CT) scans and magnetic resonance imaging (MRI) confirmed a right-sided ischemic stroke in the paramedian parietal lobe. A carotid duplex examination at the time of admission demonstrated 16% to 49% stenoses bilaterally. An echocardiogram performed 3 days later showed a hyperdynamic left ventricle with an ejection fraction of 70% to 75% and no evidence of a ventricular thrombus. While she was in the hospital, a change in mental status coinciding with a systolic BP of 250 mm Hg required the patient to be intubated for airway protection and to be transferred to the intensive care unit. The BP was subsequently brought under control using a continuous labetalol infusion. Six hours later, the patient's right arm was noted to be cold. Further examination demonstrated a lack of pulses in the right radial, ulnar, brachial, and axillary arteries. Duplex imaging confirmed an acute occlusive thrombus in the distal subclavian, axillary, and proximal brachial arteries. After an evaluation by the neurology team and a discussion of further management, the patient received a bolus of heparin, and an intravenous heparin infusion was started. An emergent open thrombectomy was performed under general anesthesia. A right brachial artery cutdown was performed, and a #3 Fogarty catheter was passed up to the level of the axillary artery. Brisk, pulsatile flow was noted after the thrombus was removed. The thrombectomy was extended distally to the level of the radial artery. No angiography was performed because of new-onset renal failure. At the end of the procedure, there was return of a strong palpable pulse. Intravenous heparin was continued postoperatively. Four days later, the patient became unresponsive, prompting a repeat CT scan, which demonstrated a large nonhemorrhagic infarct in the right middle cerebral artery distribution. Because no family members were involved and a conservator had not yet been appointed, a decompressive hemicraniectomy was performed for evidence of impending herniation. Although the patient's mental status improved, during the following weeks, she remained hemiplegic and showed no improvement in ventilator status. Given her terminal condition, the decision was made to withdraw support, and the patient subsequently died. The diagnosis of pheochromocytoma is challenging because the symptoms can be episodic and the overall incidence and index of suspicion is low. In most instances, BP control is achieved by α blockade and the causative tumor is resected. The complications resulting from catecholamine excess are usually seen in those patients with a prolonged workup before diagnosis or unresected disease. This was particularly evident in our patient, who repeatedly was noncompliant with outpatient BP management. In extreme cases, one can consider admission to the hospital and even intravenous medication use to obtain BP control before surgery. However, as our patient demonstrated, even that strategy can fail if a patient does not wish to comply with the recommendations of his or her physicians to undergo resective surgery. One of the more common complications noted in previous reports is the development of cardiomyopathy. In addition to catecholamine-induced cardiomyopathy, dilated and Takotsubo cardiomyopathy have also been reported.26Lin P.C. Hsu J.T. Chung C.M. Chang S.T. Pheochromocytoma underlying hypertension, stroke, and dilated cardiomyopathy.Tex Heart Inst J. 2007; 34: 244-246PubMed Google Scholar, 27Chia P.L. Foo D. Tako-tsubo cardiomyopathy precipitated by pheochromocytoma crisis.Cardiol J. 2011; 18: 564-567Crossref PubMed Scopus (16) Google Scholar Of those, only a small fraction are found to have an intracardiac thrombus, the major risk being subsequent embolization to the brain, kidneys, and lower extremities.2Zhou W. Ding S.F. Concurrent pheochromocytoma, ventricular tachycardia, left ventricular thrombus, and systemic embolization.Intern Med. 2009; 48: 1015-1019Crossref PubMed Scopus (19) Google Scholar, 3Hou R. Leathersich A.M. Ruud B.T. Pheochromocytoma presenting with arterial and intracardiac thrombus in a 47-year-old woman: a case report.J Med Case Rep. 2011; 5: 310Crossref PubMed Scopus (11) Google Scholar, 7Dagartzikas M.I. Sprague K. Carter G. Tobias J.D. Cerebrovascular event, dilated cardiomyopathy, and pheochromocytoma.Pediatr Emerg Care. 2002; 18: 33-35Crossref PubMed Scopus (31) Google Scholar, 9Heindel S.W. Maslow A.D. Steriti J. Mashikian J.S. A patient with intracardiac masses and an undiagnosed pheochromocytoma.J Cardiothorac Vasc Anesth. 2002; 16: 338-343Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar, 23Yebra Yebra M. Martín Asenjo R. Arrue I. Paz Yepes M. Bastante Valiente M.T. Prieto S. Acute myocardial ischemia and ventricular thrombus associated with pheochromocytoma.Rev Esp Cardiol. 2005; 58: 598-600Crossref PubMed Scopus (11) Google Scholar An examination of the existing literature on thrombotic complications of pheochromocytomas reveals several notable observations. First, the first major thrombotic event in 78% of the patients occurred coincident with the time of tumor discovery. Second, of the thrombi that do develop, 75% are located in the IVC or the heart, or both. Further, of the 13 instances involving the IVC, 11 were due to direct tumor expansion. Most of the thrombi were treated with systemic anticoagulation. Finally, we note that the tumors in these studies are quite large, ranging in size from 3.5 to 10.6 cm, with only five being <6 cm. Pheochromocytomas classically follow the “Rule of 10s”; that is, 10% are bilateral, 10% are malignant, 10% are pediatric cases, 10% are extra-adrenal, and 10% are familial. Although increasing size is often associated with an increased risk of malignancy, in tumors with local disease only, a larger size does not necessarily correlate with a higher likelihood of malignancy.28Shen W.T. Sturgeon C. Clark O.H. Duh Q.Y. Kebebew E. Should pheochromocytoma size influence surgical approach? A comparison of 90 malignant and 60 benign pheochromocytomas.Surgery. 2004; 136: 1129-1137Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar Venous thromboembolic disease is well described in pheochromocytoma patients, but only one previous published report showed an association with acute arterial thrombi.11Raghavan R. Ince P.G. Walls T.J. Gholkar A. Dark J.H. Foster J.B. Malignant cerebrovascular thromboembolization by phaeochromocytoma.Clin Neuropathol. 1995; 14: 69-71PubMed Google Scholar When looking at all causes of large-vessel arterial occlusive disease, an association has been shown with inflammatory conditions, such as Buerger disease and fibromuscular dysplasia, but the overall incidence is low and the presentation is not that of an acutely ischemic limb. In addition, acute arterial ischemia affecting the upper extremity is uncommon, occurring in only 10% to 20% of patients with acute arterial limb ischemia. Studies have demonstrated that excess catecholamines can directly contribute to hypercoagulability.29Squizzato A. Van Zaane B. Gerdes V.E. Büller H.R. The influence of pituitary, adrenal, and parathyroid hormones on hemostasis and thrombosis.Semin Thromb Hemost. 2011; 37: 41-48Crossref PubMed Scopus (10) Google Scholar, 30Haft J.I. Kranz P.D. Albert F.J. Fani K. Intravascular platelet aggregation in the heart induced by norepinephrine. Microscopic studies.Circulation. 1972; 46: 698-708Crossref PubMed Scopus (102) Google Scholar Data from ex vivo and numerous animal models demonstrate inducible platelet aggregation resulting from catecholamine infusion. Researchers in the United Kingdom demonstrated that norepinephrine resulted in platelet aggregation in two phases.31O'Brien J.R. Some effects of adrenaline and antiadrenaline compounds on platelets in vitro and in vivo.Nature. 1963; 200: 763-764Crossref PubMed Scopus (206) Google Scholar, 32O'Brien J.R. Variability in the aggregation of human platelets by adrenaline.Nature. 1964; 202: 1188-1190Crossref PubMed Scopus (47) Google Scholar Initially, the aggregation is reversible but becomes irreversible after stimulated release of adenosine diphosphate. The platelet aggregation is severe enough to cause myocardial infarction and necrosis. Administration of drugs inhibiting platelet aggregation prevents the formation of thrombus, which further prevents development of myocardial necrosis. The high catecholamine state in patients with pheochromocytoma can be very problematic. Complications, including cardiomyopathy, myocardial infarction, and stroke, have been described. We present a patient who developed an acute upper extremity arterial thrombosis that required emergent intervention. Although this was likely due to platelet aggregation stimulated by a surge in catecholamine levels, we cannot rule out the possibility of an embolus from a cardiac thrombus that was not visualized on the echocardiogram. This complication is rare, given that most patients undergo pheochromocytoma tumor resection before encountering the multiple problems that our recalcitrant patient did. It is important to remember that in patients with an unresected pheochromocytoma, acute arterial thrombosis, although rare, can occur. In addition, when an acute arterial thrombosis occurs, particularly in an unusual location, as it did in our patient, an undiagnosed pheochromocytoma should be part of the differential diagnosis.
Referência(s)