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Pheochromocytoma Presenting as Fever of Unknown Origin

Published:November 18, 2010DOI:https://doi.org/10.1016/j.amjmed.2010.05.031
      To the Editor:
      A 57-year-old man transferred to our coronary care unit for a non-ST elevation myocardial infarction complicated by acute decompensated systolic heart failure. His medical history included obesity, obstructive sleep apnea, hypertension, hyperlipidemia, tobacco use, and a 3-month history of fever of unknown origin. Prior investigation through serial outpatient visits to multiple providers was remarkable for a right adrenal “incidentaloma” with elevated erythrocyte sedimentation rate and high-sensitivity C-reactive protein. The patient was placed on a therapeutic trial of steroids for his fevers.
      Following a single dose of steroids and a salty meal, he immediately felt feverish and developed new dyspnea at rest. He went on to experience a nonradiating pressure in his mid-sternum, along with nausea, pallor, and presyncope.
      He presented to his local Emergency Department with a temperature of 37.8°C (100.0°F), blood pressure of 204/118 mm Hg, pulse of 130 beats per minute, respiratory rate of 40 breaths per minute, and an oxygen saturation of 88% on 4 L/min of supplemental oxygen. Serial electrocardiograms identified dynamic inferolateral ST depressions that improved with blood pressure control. Cardiac biomarkers were elevated and increasing (peak creatine kinase-MB 13.9 ng/mL [reference ≤5]; peak troponin I 4.84 ng/mL [≤0.012]). Chest radiograph showed bilateral infiltrates, and transthoracic echocardiogram revealed a dilated left ventricle with global hypokinesis and an estimated ejection fraction of 20%.
      Medical management of his acute coronary syndrome and diuresis improved his clinical status over 3 days, at which point he transferred to our institution. Coronary angiography demonstrated nonobstructive coronary disease. Given his overall presentation, including fever of unknown origin, adrenal mass, and paroxysmal hypertensive crises, pheochromocytoma was considered. Free normetanephrine returned 4.82 nmol/L (reference <0.90, Mayo Medical Laboratories, Rochester, MN) and metanephrine 4.03 nmol/L (<0.50), establishing, with 100% specificity,
      • Pacak K.
      • Eisenhofer G.
      • Ahlman H.
      • et al.
      Pheochromocytoma: recommendations for clinical practice from the First International Symposium October 2005.
      the diagnosis of pheochromocytoma, a catecholamine-secreting chromaffin cell tumor.
      We postulated that an endogenous catecholamine surge, combined with exogenous corticosteroid intake and salt ingestion, had increased his volume and afterload, causing demand ischemia then cardiopulmonary decompensation. Intriguingly, his left heart normalized in size and function 5 days after his initial presentation, raising the possibility of catecholamine-induced myocardial stunning, and thus overlap from a mechanistic perspective with Takotsubo cardiomyopathy.
      • Ramaraj R.
      • Sorrell V.L.
      • Marcus F.
      • Alpert J.S.
      Recently defined cardiomyopathies: a clinician's update.
      Repeat abdominal computed tomography confirmed the patient's 4.5-cm right adrenal tumor, and although there were small left renal lesions, functional imaging by 123I-labeled meta-iodobenzylguanide scan demonstrated abnormal uptake in the right adrenal only (Figure). The patient was prepared for surgery with phenoxybenzamine and metoprolol for pharmacologic blockade, titrated to orthostasis, and intravenous saline infusion to minimize volume-related fluctuations. Although the modern surgical approach is generally laporoscopic,
      • Pacak K.
      • Eisenhofer G.
      • Ahlman H.
      • et al.
      Pheochromocytoma: recommendations for clinical practice from the First International Symposium October 2005.
      open surgery was performed due to significant fibrosis from prior abdominal surgery. Adrenalectomy was successful; histopathology revealed a well-circumscribed tumor of chromaffin cells (Figure), and follow-up plasma free metanephrines normalized.
      Figure thumbnail gr1
      FigureCase patient's coronal 123I-labeled meta-iodobenzylguanide scan (right panel) demonstrating an isolated right adrenal pheochromocytoma with photomicrograph at 40× magnification of hematoxylin and eosin-stained chromaffin cells (left panel).
      Our understanding of pheochromocytomas has evolved considerably since the first case description by Felix Fränkel in 1886.
      • Fränkel F.
      Ein Fall von doppelseitigem, völlig latent verlaufenen Nebennierentumor und gleichzeitiger Nephritis mit Veränderungen am Circulationsapparat und Retinitis.
      In 2005, worldwide pheochromocytoma experts convened in Bethesda, Maryland to evaluate the state of evidence on this rare disease.
      • Pacak K.
      • Eisenhofer G.
      • Ahlman H.
      • et al.
      Pheochromocytoma: recommendations for clinical practice from the First International Symposium October 2005.
      The report provided general management recommendations and emphasized individualized care, given that pheochromocytoma presents heterogeneously. Such heterogeneity is amplified by the present case, which adds to prior atypical descriptions of pheochromocytoma with new cardiomyopathy,
      • Fränkel F.
      Ein Fall von doppelseitigem, völlig latent verlaufenen Nebennierentumor und gleichzeitiger Nephritis mit Veränderungen am Circulationsapparat und Retinitis.
      • Desai A.S.
      • Chutkow W.A.
      • Edelman E.
      • Economy K.E.
      • Dec Jr, G.W.
      Clinical problem-solving A crisis in late pregnancy.
      while taking the novel clinical angle of fever of unknown origin. The delay in diagnosis in this case and the unfortunate reality that pheochromocytoma is diagnosed at autopsy in half of cases
      • Pacak K.
      • Eisenhofer G.
      • Ahlman H.
      • et al.
      Pheochromocytoma: recommendations for clinical practice from the First International Symposium October 2005.
      stress the need for increased appreciation for the variability in clinical patterns of presentation, particularly because pheochromocytoma is a curable disease when detected early.

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