Left Ventricular Thrombus and Embolic Stroke Caused by a Functional Paraganglioma

Pheochromocytoma and functional paraganglioma are uncommon causes of secondary hypertension. In rare instances, these catecholamine‐secreting tumors present as atypical and dramatic symptoms without clear history of hypertension. We describe here LV thrombus and embolic stroke caused by a functional paraganglioma.

Case History

A 49‐year‐old Caucasian man was admitted for elective transesophageal echocardiography to examine whether he had a patent foramen ovale. One month before this admission, the patient had flu‐like symptoms, left upper quadrant abdominal pain, and constipation for 2 weeks. He then developed a 1‐minute episode of garbled speech and left upper extremity weakness that lasted for 24 hours. He was admitted into another hospital. An abdominal computed tomography (CT) scan revealed a large left retroperitoneal mass and multiple left renal infarcts. A head CT suggested stroke. Since the renal and brain infarcts suggested an embolic etiology, transthoracic echocardiography was performed, which detected a 1.3×1.9 cm mobile mass in the mid left ventricle apparently attached to the interventricular septum (Figure 1, Left). Also noted was reduction of left apical wall motion. Transesophageal echocardiography was performed at the other hospital without complications and confirmed the transthoracic findings. On electrocardiography (ECG), the patient exhibited a prolonged QT interval and diffuse T‐wave abnormalities especially on the precordial leads without evidence of atrial fibrillation (Figure 1, Right). Troponin levels were mildly elevated to 0.07 ng/mL (normal <0.05 ng/mL). Coronary angiography revealed normal coronary arteries. He was anticoagulated with heparin, then warfarin and enoxaparin, and was treated with metoprolol due to the abnormal ECG findings. On repeat echocardiography and cardiac magnetic resonance imaging (MRI) 2 to 3 weeks later, the left ventricular (LV) mass was not seen, but LV systolic function was still abnormal, with an ejection fraction of 47%. The distal left ventricle and apex thickened during diastole but moved dyskinetically during early systole.

Figure 1.

 (Left) Left ventricular mass identified on transthoracic echocardiography. The mobile pedunculated mass measured 1.3×1.9 cm (arrow). (Right) A representative electrocardiogram at initial presentation. It showed diffuse T‐wave abnormalities especially on the precordial leads and prolonged QT interval with a QTc of 507 milliseconds.

Paraganglioma was not considered for the retroperitoneal mass. CT‐guided core biopsy was performed without complication and pathologic examination initially suggested metastatic carcinoma. Combined positron emission tomography/CT identified the retroperitoneal mass as the only lesion that avidly took up fluorodeoxyglucose. Later, re‐examination at this hospital revealed histology consistent with paraganglioma. Repeat MRI studies confirmed earlier results (Figure 2, Top). The patient’s blood pressure was reportedly normal and he denied a history of headache, palpitations, sweating, lightheadedness, or chest pain. The paraganglioma was considered functionally inactive, and markers for functional paraganglioma were ordered. He had not been treated with an α‐blocker. His medical history included decreased exercise tolerance for a year. Multiple family members had history of cancer but none had a history of endocrine neoplasia. Physical examination was only remarkable for blood pressure of 148/90 mm Hg and a 2/6 midsystolic murmur.

Figure 2.

 (Top) Magnetic resonance images of abdomen and brain. (A) A heterogeneously enhancing left retroperitoneal mass measuring 7.7×5.2×7.7 cm (arrow). (B) A wedge‐shaped area of left renal cortical hypoperfusion (arrow). (C) An infarct in the right cerebellum (arrow). (Bottom) Paraganglioma before (left) and after (right) resection. The paraganglioma (thick arrow) invaded the renal vein (thin arrow).

Due to the absence of significant hypertension, the patient was tentatively diagnosed with a nonfunctional paraganglioma and possible paradoxical embolism and admitted for an elective transesophageal echocardiogram to examine whether he had a patent foramen ovale. The etiology of abnormal cardiac findings was not clear. The transesophageal echocardiogram with bubble study did not find any intraventricular mass or evidence of a right‐to‐left shunt. At the end of the procedure, the patient became markedly hypertensive with blood pressures as high as 240/120 mm Hg. In addition, he experienced severe headache, photophobia, and vomiting. He was treated with multiple antihypertensive medications including nitroglycerin, esmolol, amlodipine, and phenoxybenzamine. Plasma normetanephrine was extremely elevated at 55.9 nmol/L (normal <0.9 nmol/L) and plasma metanephrine was normal at 0.29 nmol/L (normal <0.5 nmol/L). Chromogranin levels were 145.4 ng/mL (normal <36.4 ng/mL). Hypercoagulability panel was remarkable only for mildly elevated anticardiolipin IgG. The patient was prepared preoperatively with phenoxybenzamine, labetalol, and intravenous fluid and underwent resection of the paraganglioma with an in‐continuity left nephrectomy (as the tumor invaded the renal vein) (Figure 2, Bottom). The postoperative period was uneventful except for mild orthostatic hypotension. The plasma metanephrine levels, ECG, and echocardiographic findings returned to normal.

Discussion

In this report we describe LV thrombus as a complication of a functional paraganglioma. Paragangliomas are tumors derived from paraganglia tissue within the autonomic nervous system. Most abdominal paragangliomas are derived from sympathetic paraganglia and tend to be functional in that they secrete catecholamines. ¹ Functional paragangliomas are morphologically and functionally similar to pheochromocytomas, which are paragangliomas derived from the adrenal medulla. They are well known to cause cardiovascular complications including hypertension, stroke, cardiomyopathy, and cardiogenic shock. ² The cardiomyopathy caused by a pheochromocytoma or a functional paraganglioma resembles stress‐induced cardiomyopathy (Takotsubo cardiomyopathy) since both types of cardiomyopathy are associated with catecholamine excess. ³ , ⁴

To our knowledge, only 3 cases of LV thrombus associated with a pheochromocytoma have been reported in the English literature. ⁵ , ⁶ , ⁷ One case describes an 18‐year‐old woman with multiple endocrine neoplasia type 2 who had both medullary thyroid carcinoma and pheochromocytoma. ⁵ Her LV thrombus was incidentally identified and she exhibited normal LV function and wall motion. The other 2 cases and our case share common features, which are summarized in the Table. ⁶ , ⁷ All 3 patients were middle‐aged men with an apparently isolated pheochromocytoma or functional paraganglioma. They presented with varied symptoms such as pneumonia, embolic stroke, and paroxysmal spells. Two patients had history of hypertension while our patient did not. None were previously suspected to harbor a pheochromocytoma or a functional paraganglioma. Catecholamine‐secreting tumors were considered only after hypertensive crisis. All patients developed an embolic stroke during their clinical course. Abnormal ECG findings in the 3 patients were remarkably similar with diffuse T‐wave abnormalities and prolonged QT interval, suggesting repolarization defects. The patients all exhibited LV wall motion abnormalities and decreased ejection fraction with normal coronary arteries, consistent with Takotsubo cardiomyopathy or its variants. Their catecholamine‐secreting tumors were rather sizable and produced a large amount of catecholamine. Remarkably, all cardiac abnormalities reverted to normal after tumor resection.

Table.

 Comparison of 3 Cases of Left Ventricular Thrombus and Embolic Stroke Associated With Pheochromocytoma or Functional Paraganglioma

	Heindel et al 6	Yebra Yebra et al 7	Buchbinder et al (Current Case)
Age, y	49	59	49
Sex	Male	Male	Male
Presentation	Pneumonia	Paroxysm	Abdominal pain, Dysphasia, Weakness
History of hypertension	Yes	Yes	No
Embolic stroke	Yes	Yes	Yes
Electrocardiography findings
QT interval	Not described	Prolonged	Prolonged
T wave	Diffuse T‐wave changes	T‐wave inversion	T‐wave inversion
LV function
Wall motion	Diffuse hypokinesis	Apical akinesia	Mild hypokinesis
Ejection fraction	40%–50%	25%	47%
Recovery after tumor resection	Complete	Complete	Complete
LV thrombus
Number	3	1	1
Morphology	Mobile, pedunculated	Adhering	Mobile, pedunculated
Size, cm	0.5–1.0	0.6×3.0	1.3×1.9
Position	Apex	Apex, posterior wall	Interventricular septum
Response to anticoagulation	Resolved	Resolved	Resolved
Coronary angiography	Normal	Normal	Normal
Underlying tumor	Pheochromocytoma	Pheochromocytoma	Functional paraganglioma
How diagnosis was invoked	Hypertensive crisis during surgery to remove LV masses	Hypertension and paroxysm	Hypertensive crisis during transesophageal echocardiogram
Tumor
Size, cm	10	3.5	7.7×5.2×7.7
Side	Left	Left	Left
Biochemical markers	Elevated	Elevated	Elevated

Abbreviation: LV, left ventricular.

These cases illustrate the natural history of LV thrombus in patients with pheochromocytoma or functional paraganglioma. It tends to occur in middle‐aged men with left‐sided, large catecholamine‐secreting tumors. Cardiogenic embolism causes significant neurologic and other visceral damages. Unlike the LV thrombus seen in patients with common LV dysfunction, ⁸ the LV thrombus in patients with a functional paraganglioma is not associated with ischemic cardiomyopathy or LV enlargement. Rather, it is associated with abnormalities of LV wall motion and repolarization. The mechanisms for LV thrombus formation are likely related to abnormal blood flow pattern as in Takotsubo cardiomyopathy. ⁹ , ¹⁰ The LV thrombus is amenable to anticoagulation therapy and the underlying cardiomyopathy is completely reversible following tumor resection. We therefore recommend a high index of clinical suspicion of a functional paraganglioma in all patients with an LV mass and abnormalities in LV wall motion and repolarization. Conversely, an LV mass in patients with catecholamine‐secreting tumors and diffuse T‐wave abnormalities is probably a thrombus and a trial of anticoagulation should be instituted, which can potentially prevent cardiogenic embolism.

In summary, our case and 2 similar cases in the English literature establish a clinical syndrome of LV thrombus in patients with a pheochromocytoma or a functional paraganglioma. These catecholamine‐secreting tumors should be suspected in patients with an LV mass and specific ECG and echocardiographic abnormalities. Conversely, LV thrombus should be screened for in patients with these tumors and the appropriate ECG findings. As pheochromocytoma and functional paraganglioma are treatable diseases and the embolic damage of LV thrombus is potentially preventable, it is important to consider this clinical syndrome in their differential diagnosis.