Thinking Outside the Heart: Pheochromocytoma as a Rare Cause of Dilated Cardiomyopathy

A 42-year-old woman presented to the emergency department with a 2-week history of progressive dyspnea. She also described paroxysmal episodes of palpitations, sweating, and nervousness within the last few months. Physical examination revealed jugular venous engorgement, painful hepatomegaly, and bilateral lung crackles. An electrocardiogram showed sinus tachycardia, narrow QRS complexes, and lateral T-wave inversion. N-terminal pro brain natriuretic peptide (NT-proBNP) was elevated at 5738 pg/mL (reference range <125 pg/mL). A transthoracic echocardiogram revealed a dilated left ventricle with severe systolic dysfunction and moderate secondary mitral regurgitation. As part of the diagnostic workup, cardiac magnetic resonance (CMR) imaging and endomyocardial biopsy were performed. CMR imaging demonstrated a dilated left ventricle with a severely depressed left ventricular ejection fraction, diffuse myocardial edema on T2-weighted sequences, and septal midwall late gadolinium enhancement. A thorough physical examination was performed due to persistent right-sided abdominal discomfort, and an abdominal mass was palpated. This was subsequently assessed by abdominal ultrasound, which identified a right adrenal lesion. The previous CMR images were revisited and confirmed the presence of the mass, which was characterized by hyperintensity on T2-weighted sequences and early enhancement of the first-pass perfusion sequence, suggestive of a solid lesion. An abdominal computed tomography scan was carried out to assist with surgical planning, and this identified a 4-cm heterogeneous right-sided adrenal tumor (Figure A). Given the clinical and imaging data, pheochromocytoma was suspected. Endocrine function testing was performed and showed elevated levels of urine metanephrines and normetanephrine (2303 ug/L and 6911 ug/L, respectively, with normal reference range from 0.0 to 0.0), diagnostic of pheochromocytoma. Regarding the endomyocardial biopsy, myocardial fat infiltration was found, with subtle areas of fibrosis and findings suggestive of chronic myocarditis, as macrophages and CD3+ lymphocytes were identified using immunohistochemistry techniques (Figure B). Clinical evolution during the admission was favorable. Pharmacological alpha-blockade was initiated, in addition to low-dose metoprolol and eplerenone. Finally, successful laparoscopic right adrenalectomy was performed 1 month later, and the alpha-blocker was withheld and low-dose ramipril started. A histological study of the tumor demonstrated an adrenal neoplasia consistent with pheochromocytoma (Figures C and D). Three months after surgery, the patient remained in New York Heart Association functional class I, and N-terminal pro brain natriuretic peptide levels dropped to 165 pg/mL. A transthoracic echocardiogram was performed and showed complete normalization of the left ventricular ejection fraction and left ventricular volumes and correction of secondary mitral regurgitation. Likewise, metanephrine levels returned to the normal range. Pheochromocytoma is a rare neuroendocrine tumor, characterized by the secretion of catecholamines, originating from chromaffin cells of the adrenal medulla or extra-adrenal paraganglia.1Lenders JW Eisenhofer G Mannelli M Pacak K. Phaeochromocytoma.Lancet. 2005; 366: 665-675Abstract Full Text Full Text PDF PubMed Scopus (1325) Google Scholar These tumors often induce alterations in myocardial structure and function, and various cardiac pathologies have been described, including cardiac hypertrophy, stress-induced cardiomyopathy, myocarditis, and dilated cardiomyopathy.2Japp AG Gulati A Cook SA Cowie MR Prasad SK. The diagnosis and evaluation of dilated cardiomyopathy.J Am Coll Cardiol. 2016; 67: 2996-3010Crossref PubMed Scopus (258) Google Scholar,3Ferreira VM Marcelino M Piechnik SK et al.Pheochromocytoma is characterized by catecholamine-mediated myocarditis, focal and diffuse myocardial fibrosis, and myocardial dysfunction.J Am Coll Cardiol. 2016; 67: 2364-2374Crossref PubMed Scopus (105) Google Scholar The cardiac effects of pheochromocytoma go beyond the influence of hypertension alone, as long-term elevation of catecholamines leads to downregulation of β-adrenergic receptors, inducing impaired function of cardiomyocytes.3Ferreira VM Marcelino M Piechnik SK et al.Pheochromocytoma is characterized by catecholamine-mediated myocarditis, focal and diffuse myocardial fibrosis, and myocardial dysfunction.J Am Coll Cardiol. 2016; 67: 2364-2374Crossref PubMed Scopus (105) Google Scholar Our patient did not present with hypertension, even prior to the initiation of treatment, and it is known that 10% of patients may have normal blood pressure. In addition, catecholamines can alter the extracellular matrix with collagen deposition and subsequent myocardial fibrosis, which can be detected by late gadolinium enhancement-CMR imaging in a significant proportion of patients with pheochromocytoma.3Ferreira VM Marcelino M Piechnik SK et al.Pheochromocytoma is characterized by catecholamine-mediated myocarditis, focal and diffuse myocardial fibrosis, and myocardial dysfunction.J Am Coll Cardiol. 2016; 67: 2364-2374Crossref PubMed Scopus (105) Google Scholar This case illustrates the pathophysiology of catecholamine-induced cardiac toxicity secondary to pheochromocytoma as a rare but potentially reversible cause of dilated cardiomyopathy. Multimodality imaging has a significant role in the diagnosis of cardiomyopathies. Nevertheless, in parallel to the use of imaging techniques, clinical suspicion and a thorough physical examination are vital to establish the correct diagnosis because the classic symptom triad of headache, palpitations, and diaphoresis are often absent in most patients.