Case Report  |   August 2017
Pheochromocytoma-Induced Cardiomyopathy Mimicking Acute Coronary Syndrome
Author Notes
  • Financial Disclosures: None reported. 
  • Support: None reported. 
  •  *Address correspondence to Viliane Vilcant, MBS, DO, Samaritan Medical Center, 830 Washington St, Watertown, NY 13601-4034. Email:
Article Information
Cardiovascular Disorders / Endocrinology
Case Report   |   August 2017
Pheochromocytoma-Induced Cardiomyopathy Mimicking Acute Coronary Syndrome
The Journal of the American Osteopathic Association, August 2017, Vol. 117, 537-540. doi:
The Journal of the American Osteopathic Association, August 2017, Vol. 117, 537-540. doi:
Web of Science® Times Cited: 3

Pheochromocytoma is a rare catecholamine-secreting tumor with a prevalence of 0.1% to 0.6% in hypertensive patients. The classic triad of symptoms is headache, palpitations, and diaphoresis, but clinical presentation varies greatly. Pheochromocytoma can also mimic acute coronary syndrome and heart failure. With surgical resection, appropriate preoperative medical therapy, and 10% malignancy rate, prognosis is usually good. In the present case, a patient presented to the emergency department with symptoms suggesting a non–ST-segment elevation myocardial infarction and was transferred to a tertiary medical center for a cardiac catheterization. No coronary artery disease was found. However, cardiomyopathy developed, which made pheochromocytoma difficult to diagnose at first glance.

Pheochromocytoma is a well-vascularized catecholamine-secreting tumor that arises from chromaffin cells of the adrenal medulla. These tumors are rare, with an estimated prevalence of 0.1% to 0.6% in patients with hypertension and an annual incidence of 2 to 8 cases per 1 million people.1,2 At least 10% are malignant, and 10% to 20% are familial.2,3 The mean age of diagnosis is about 40 years.3 The classic triad of symptoms is headache, palpitations, and diaphoresis; however, pheochromocytoma can be asymptomatic for years.3 Other signs and symptoms that can occur include nausea, vomiting, weight loss, shortness of breath, chest pain, tremor, hypertension, and pulmonary edema. 
In the current report, I describe the case of a patient who presented with symptoms suggestive of acute coronary syndrome. Cardiac catheterization revealed no obstructive disease, which allowed for further evaluation of symptoms leading to the diagnosis of pheochromocytoma-induced cardiomyopathy—not only a rare disease, but also a rare presentation of the disease. 
Report of Case
A 55-year-old white woman with a medical history notable for thyroid cancer (managed with thyroidectomy), subsequent hypothyroidism, and hypertension presented to the emergency department with acute symptoms of chest pain, nausea, and dizziness. The patient was diaphoretic and hypotensive, which improved after fluid resuscitation. She denied headache, palpitations, and shortness of breath. Her systolic blood pressure (mm Hg) was in the 90s, but all other vital signs were stable. Results of laboratory studies revealed elevated D-dimer of 531 ng/mL (reference range, <500 ng/mL) and elevated troponin of 2.65 ng/mL (reference range, <0.02 ng/mL). An electrocardiogram did not show any acute ST-T wave changes. With the presumed diagnosis of non–ST-segment elevation myocardial infarction, she was transferred for higher level of care. While at the tertiary medical center, she continued to have persistent chest discomfort despite administration of 0.4 mg of sublingual nitroglycerin and 4 mg of morphine. Troponin levels remained elevated. The patient was taken for cardiac catheterization with possible revascularization. An angiogram revealed anterobasal and anterolateral akinesis with an ejection fraction of 35% to 40%. No evidence of coronary artery disease was found and no intervention was indicated. Her symptoms improved, and she was discharged from the hospital 2 days after presentation with recommendation for routine follow-up. 
Seven days after hospital discharge, the patient presented to the emergency department again with symptoms of atypical chest pain with associated nausea and diaphoresis. In addition, she reported shortness of breath, headache, and blurry vision. Physical examination revealed elevated blood pressure and occasional tachycardia, but all other findings were benign. Chest radiograph showed perihilar and lower base opacities suggestive of pulmonary edema and pulmonary congestion. With these additional symptoms and findings, computed tomography of the abdomen was ordered, the results of which revealed an 8.5-cm solid ovoid mass in the right adrenal gland (Figure). Laboratory data revealed a plasma metanephrine level of 247 pg/mL (reference range, 0-62 pg/mL); plasma normetanephrine, 1710 pg/mL (reference range, 0-145 pg/mL); urinary metanephrine, 852 μg/24 h (reference range, 45-290 μg/24 h); and 24-hour urine normetanephrine, 2916 μg/24 h (reference range, 82-500 μg/24 h). With evidence of biochemical pheochromocytoma and a right adrenal mass, she was referred to a surgeon for resection and discharged from the hospital. In the interim, she began phenoxybenzamine therapy (10 mg twice daily), which was well tolerated. After 3 days, a β blocker (metoprolol, 12.5 mg daily) was added to better control her tachycardia. One week after her second presentation to the emergency department, the adrenal mass was surgically removed and the patient had an uneventful recovery. Repeated echocardiogram 1 month after surgery showed resolution of all wall motion abnormalities and preserved left ventricular ejection fraction. Her hypertension also resolved and her blood pressure medications were discontinued. 
Abdominal computed tomographic image revealed a solid ovoid mass (8.5 × 7.9 cm) in the right adrenal gland of a patient presenting with symptoms suggestive of a non–ST-segment elevation myocardial infarction.
Abdominal computed tomographic image revealed a solid ovoid mass (8.5 × 7.9 cm) in the right adrenal gland of a patient presenting with symptoms suggestive of a non–ST-segment elevation myocardial infarction.
Patients with pheochromocytoma excrete excess amounts of epinephrine, norepinephrine, and dopamine in the urine, causing them to have symptoms that can be constant or episodic. Hypertension develops as a result of the overdrive of the sympathetic system, which causes excessive catecholamine release. Diagnosis of pheochromocytoma is thus typically confirmed biochemically with measurements of urinary and plasma metanephrine and catecholamines, with localization of the mass achieved by means of magnetic resonance imaging or computed tomography.1,3 Once confirmed and located, standard treatment is complete surgical resection. Surgical survival rates are 98% to 100%.1 An α-adrenergic blocker (typically phenoxybenzamine) is usually given 7 to 10 days before the operation to normalize blood pressure and expand the contracted blood volume.1 After adequate α blockade, β blockade is initiated 2 to 3 days preoperatively to help control tachycardia. Osteopathic physicians may be able to use osteopathic manipulative treatment to normalize sympathetic outflow and remove any restriction to the parasympathetic activity. Craniosacral manipulation and treatment of the patient's atlantooccipital and cervical regions can be used to balance the autonomic nervous system and alter vagal response while awaiting surgical intervention. 
Clinical presentation of pheochromocytoma can mimic acute coronary syndrome, but coronary arteriography typically reveals no obstructive disease.4-6 Electrocardiographic abnormalities in pheochromocytoma may include ST-segment elevations, T-wave inversions, and abnormal Q waves; however, in many cases, electrocardiogram results may be normal.7,8 Troponin levels are usually elevated, but elevations are mild. Rarely, pheochromocytoma is associated with a transient cardiomyopathy that is similar to stress-induced (takotsubo) cardiomyopathy, as it was in this case. In contrast to acute coronary syndrome, stress-induced cardiomyopathy goes beyond a single coronary artery perfusion area.7 Several mechanisms have been proposed for stress-induced cardiomyopathy, including direct catecholamine toxicity to the myocytes causing nonischemic myocardial stunning,9 excess sympathetic activation leading to necrosis, diffuse coronary vasospasm, microvascular impairment of the coronary arteries, and impaired fatty acid metabolism. Catecholamine-induced cardiotoxicity and microvasculature dysfunction are the most supported theories.7 
In the catecholamine-induced cardiotoxicity theory, a decline in myocyte contractile function occurs due to catecholamines inducing β2-coupling from the Gs protein to the Gi protein.7,10 The rationale is that a switch to the Gi protein protects the myocytes from the strong stimulation of the Gs protein, which causes apoptosis.7 However, this switch is negatively inotropic,7 which causes hypokinesis of the heart muscle. In stress-induced cardiomyopathy, this effect is greatest at the apical myocardium, where the β-adrenoceptor density is the highest. The phosphatidyl inositol 3-kinase-protein kinase B (PI3K/Akt) signaling pathway, which has antiapoptotic effects, is then activated, which leads to switching from the Gi protein back to the Gs protein and thus accounts for transient left ventricular dysfunction.7,10 The other most supported theory—microvasculature dysfunction—proposes that stress-induced cardiomyopathy is caused by abnormalities in endothelium-dependent vasodilation, leading to excessive vasoconstriction and impaired myocardial perfusion.10 
In the present case, the patient developed nonischemic cardiomyopathy leading to heart failure, and echocardiogram revealed anterobasal and anterolateral akinesis with moderate left ventricular systolic dysfunction. In stress-induced cardiomyopathy, there is typically hypokinesis or akinesis of the mid and apical segments and hyperkinesis of the basal segments.11 However, there is also a basal type of stress-induced cardiomyopathy in which hypokinesis of the basal segment exists (known as atypical cardiomyopathy or inverted takotsubo cardiomyopathy). An even rarer focal or localized type also exists that causes dysfunction of the anterolateral segment.12 The cardiomyopathy in this case would fit into the focal type, but stress-induced cardiomyopathy cannot be diagnosed in the setting of pheochromocytoma. In both diagnoses, the catecholamine cardiotoxic effects are parallel. 
Once diagnosis is confirmed and surgical resection is performed, cardiomyopathy usually resolves.1 Stable patients are often treated with diuretics, angiotensin-converting enzyme inhibitors, and β blockers, which is the standard drug therapy regimen for heart failure. Anticoagulation therapy could be considered in patients with hypokinesia until the contractility of the heart muscle is restored.7 Systolic function typically recovers in 1 to 4 weeks. Patients should have annual biochemical screening to assess for metastatic disease and recurrence or delayed appearance of primary tumors.1 Recurrence is more likely in patients with familial pheochromocytoma, familial paraganglioma, right adrenal tumors, and extra-adrenal tumors. Patients with a risk for recurrence may take a β blocker or combined α and β blocker indefinitely. 
Pheochromocytoma may be associated with familial syndromes such as multiple endocrine neoplasia (MEN), von Hippel-Lindau disease, and neurofibromatosis type I,13 making diagnosis even more important. The patient in the present case had a history of thyroid cancer; however, it was not the medullary type, which is most commonly associated with MEN. Patients with pheochromocytoma associated with genetic disorders usually present at a younger age. It occurs in 50% of patients with MEN type 2, 20% to 30% of those with von Hippel-Lindau disease, and about 1% of patients with neurofibromatosis type I.3 A medical history of hyperparathyroidism or elevated calcium levels should prompt a suspicion of MEN type 2A, and a history of mucocutaneous neuromas or musculoskeletal abnormalities should prompt an evaluation for MEN type 2B. Likewise, screening for von Hippel-Lindau disease should be considered in patients with a history of paraganglioma, hemangioblastoma, retinal angioma, or clear cell renal carcinoma. Screening for neurofibromatosis type I should be performed in patients with a history of neurofibromas, café au lait spots, inguinal/axillary freckling, or iris hamartomas. These disorders are autosomal dominant, and genetic testing is usually considered if patients have pheochromocytoma at a young age, bilateral adrenal pheochromocytoma, a first-degree relative with pheochromocytoma, paragangliomas,1 or other clinical signs of the aforementioned genetic disorders. 
Pheochromocytoma can have variable presentations, including acute myocardial infarction, heart failure, hypertensive emergency, and anxiety. The cardiomyopathy that develops can resemble the presentation of acute coronary syndrome. Once acute coronary syndrome has been ruled out, pheochromocytoma should be included in the differential diagnosis. Cardiomyopathy and congestive heart failure are the symptomatic presentations of pheochromocytoma that are most frequently unrecognized by physicians.1 Therefore, when patients have uncontrolled hypertension, physicians should keep this condition in mind. Pheochromocytoma is rare, and most people who are tested biochemically do not have it. However, the present case reminds physicians to be aware of its many presentations to allow for early diagnosis and treatment before cardiac complications arise. 
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Suh IW, Lee CW, Kim YH, et al.   Catastrophic catecholamine-induced cardiomyopathy mimicking acute myocardial infarction, rescued by extracorporeal membrane oxygenation (ECMO) in pheochromocytoma. J Korean Med Sci. 2008;23(2):350-354. [CrossRef] [PubMed]
Sanchez-Recalde A, Costero O, Oliver JM, Iborra C, Ruiz E, Sobrino JA. Pheochromocytoma-related cardiomyopathy: inverted takotsubo contractile pattern. Circulation. 2006;113(17):e738-e739. [CrossRef] [PubMed]
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Abdominal computed tomographic image revealed a solid ovoid mass (8.5 × 7.9 cm) in the right adrenal gland of a patient presenting with symptoms suggestive of a non–ST-segment elevation myocardial infarction.
Abdominal computed tomographic image revealed a solid ovoid mass (8.5 × 7.9 cm) in the right adrenal gland of a patient presenting with symptoms suggestive of a non–ST-segment elevation myocardial infarction.