Pheochromocytoma is a rare neuroendocrine tumor characterized by excessive secretion of catecholamines. Classic symptoms are tachycardia, headache, hypertension, and sweating.1 Although rare, cardiogenic shock represents a severe complication, and in that case, the timing of tumor resection is challenging.2 We report the case of a patient who developed a severe catecholamine-induced cardiomyopathy secondary to a pheochromocytoma. Despite significant cardiac recovery, the patient remained in respiratory failure with hemoptysis and bilateral pleural effusions. The resolution of these symptoms seemed to accelerate following surgical resection of the tumor, performed several weeks after the initial episode. Mr B is a 53-year-old man with no previous cardiovascular history (except varicose vein stripping) and no known endocrine disorders. He presented to the emergency department with abdominal pain, headache, dysuria, asthenia, and diaphoresis. An injected abdominopelvic computed tomography (CT) scan showed a large left adrenal nodule. Finally, the thoracic CT scan showed ground-glass opacities with an interlobular thickening, compatible with pulmonary edema. The patient was dyspneic and hypoxic (saturation of peripheral oxygen around 65%) despite the use of a high oxygen concentration mask, and his lower limbs became mottled. The patient was then orally intubated and mechanically ventilated. Blood tests showed troponin I, 112464.4 ng/L; N-terminal pro brain natriuretic peptide, 4441 pg/mL; creatinine, 228 µg/L; lactate, 8.4 mmol/L; and kaliemia, 3.4 mmol/L. Transthoracic echocardiography (TTE) showed an altered left ventricular ejection fraction (LVEF) of approximatively 10%, with an enlarged left ventricle. Takotsubo syndrome (TTS) was suspected. Dobutamine and norepinephrine were introduced and gradually increased, but the patient remained hemodynamically unstable, so an extracorporeal life support (ECLS) was implemented. Subsequently, we noticed an improvement in his hemodynamic status, with an ECLS output of 4 L/min. Antibiotics were started due to an important vasoplegia. At the beginning of the intensive care unit (ICU) stay, cardiac and respiratory functions improved enough to remove the ECLS after 6 days. At the same time, dobutamine was decreased and stopped after 10 days of administration, but norepinephrine was maintained. A coronarography ruled out coronary disease. Blood tests supported a pheochromocytoma, showing positive results: normetanephrine, 26,806 nmol/24 h; metanephrine, 101,088 nmol/24 h, and 3-methoxytyramine, 3816 nmol/24 h. Subsequently, he developed several ventilator-associated pneumonias, with septic shocks. This precluded the use of alpha- and beta-blockers, which were essential to prepare the patient for surgery and prevent perioperative hemodynamic complications. Consequently, the pheochromocytoma resection was delayed. At the metabolic level, the patient initially showed an improvement in acute kidney injury, but along with septic shocks, he had a new deterioration, up to kidney disease improving global outcomes 3 (creatinine: 384 µmol/L), requiring renal replacement therapy. This was associated with proteinuria (2.01 g/L) and hypoproteinemia (47 g/L). A myelogram excluded a hemophagocytic syndrome. He also presented continuous bilateral pleural effusions, needing multiple thoracic drainages, with large amounts of citrine fluid drained, up to 3 L/d (Fig. 1). The biochemical tests of these pleural effusions were in favor of a transudate (protein: 10.2 g/L). At the same time, hemoptoic secretions appeared, while he did not present hypertension (even needing sometimes a vasopressor support) or a hemostasis disorder. A thorough search for signs of vasculitis was conducted, and the results of the blood tests did not support the diagnosis.Figure 1.: Evolution of pleural effusions from admission to day 50 (the arrow indicates the surgical resection). ICU, intensive care unit.We performed a bronchoalveolar lavage, but it showed only red blood cells (74,400/mm3). The bronchoscopy revealed active bleeding in the posterior segment of the right upper lobar bronchus (B2), and an embolization stopped the hemorrhage, resulting in only minor hemoptoic secretions during the following week. During this time, the patient’s cardiac function improved, but it was not fully normalized, and a TTE performed at day 35 showed a LVEF of 30% with low left ventricle filling pressure. He also had pulmonary edema, showed by daily radiographies and by a CT scan performed at day 22. The enhancement of the patient’s hemodynamic status enabled the initiation of an alpha-blocker (Urapidil) 29 days after the admission and a beta-blocker (Esmolol) 37 days after the admission. Surgery of the pheochromocytoma was performed 41 days after the admission in critical care unit. Surgery was performed without incident or hypertensive crisis. The pathological analysis confirmed a pheochromocytoma. Interestingly, the patient presented no more hemoptysis and a substantial drop in pleural effusions after the removal (Fig. 1). A CT scan carried out 46 days after admission revealed 2 pleuro-pulmonary abscesses related to drainages. Extubation occurred 63 days after admission. After 81 days of stay, Mr B was discharged from the ICU. A TTE performed at day 85 showed a LVEF of 36%. Then, the patient went to a rehabilitation center, and he recovered a good cardiac function (LVEF at day 111 = 50%). At day 134, the patient had a follow-up consultation that showed a good muscular and respiratory recovery, and a normal pressure profile. Pheochromocytomas are rare neuroendocrine tumors, belonging to the group of pheochromocytomas and paragangliomas, and represent 80%–85% of this group. The incidence of diagnosed pheochromocytomas is increasing and is estimated around 0.5 per 100,000 person-years.3 The incidence in a hypertensive population is about 0.1%–0.6%.4 Pheochromocytomas are known to synthesize catecholamines (essentially epinephrine for 80% and norepinephrine for 20%) via the adrenal medulla. Catecholamines bind to alpha and beta receptors, explaining the symptomatology of pheochromocytomas: activation of alpha receptors increases blood pressure via a peripheral vasoconstriction, and stimulation of beta receptors has a chronotrope and an inotrope effect on the heart, along with sweating. Sometimes, a high level of catecholamines can lead to more severe cardiovascular symptoms: hypertensive crisis, tachyarrhythmia, and myocardiopathy as TTS.5 TTS occurs in 8%–11% of pheochromocytoma cases.5 It is characterized by a left ventricular dysfunction presenting as apical ballooning, with no argument for an acute myocardial infarction.6 In case of pheochromocytoma, the physiopathology seems to be explained by an imbalance between the myocardial oxygen uptake and demand.5 It can be extremely severe and can lead to cardiogenic shock, needing sometimes ECLS.7 We described a case of severe TTS due to a pheochromocytoma, with long-term complications. The history of this patient was not typical: although he had a headache and diaphoresis, he never had hypertension (even during the tumor removal). The issue was, in fact, a hypotension, which required a vasopressor support and delayed the administration of alpha- and beta-blockers. Other cases of pheochromocytoma-induced TTS have been reported.2 Some patients presented symptoms similar to Mr B, such as headache and diaphoresis, with cardiogenic shock,2 sometimes requiring ECLS.7 Others had pheochromocytoma with hemoptysis8,9 or pulmonary edema,10 but we found no case combining pheochromocytoma, TTS, hemoptysis, and pleural effusions. Hemoptysis presented by Mr B has not been explained by any autoimmune pathology. The way pheochromocytomas can lead to hemoptysis (excluding left ventricular failure and hypertensive pulmonary edema) is not well known, but pulmonary hypertension, endothelial dysfunction,8 and abnormal clotting11 could play a role. In most cases, as with our patient, removal of the tumor is followed by cessation of hemoptysis. Persistent pleural effusion was another complication. Numerous etiological pathways have been investigated. There was no argument for an autoimmune etiology. Hypoproteinemia caused by proteinuria could have led to a decrease in the oncotic pressure, and thus generate pleural effusion. Proteinuria has yet been described in patients with a pheochromocytoma12 and may be due to acute tubular necrosis caused by sudden blood pressure changes or to glomerular injuries. An alternative hypothesis is pulmonary fluid overload, as pheochromocytomas have been shown to induce pulmonary edema.10 In this case, cardiac dysfunction could not explain the symptoms fully because left ventricle filling pressure remained low. Catecholamines could play a direct role in the pulmonary vascular bed,10 but this pathway remains unclear. In our case, the sudden decrease after the pheochromocytoma removal lends support to this hypothesis. Finally, our patient had a cardiac dysfunction until the resection, which could explain the hemodynamic instability observed during all his stay in ICU and (at least partly) both effusions and hemoptysis. The pheochromocytoma-induced TTS seems to differ from other TTS because the underlying cause remains until the resection, with a continuous excessive amount of catecholamines. Studies have established that pheochromocytomas can cause chronic cardiomyopathies13 and that resection improves the LVEF for more than 90% of pheochromocytoma-induced cardiomyopathies.2 Optimal timing of surgery remains debated, and several approaches have been outlined, ranging from the emergency resection to the delayed resection.14 In case of a severe cardiac failure, a delayed surgery seems a good way to optimize the hemodynamic status, allowing the preparation with alpha- and beta-blockers before the surgery.15 In any case, even if the symptoms can improve with time, the resection should always be considered because of the impact on cardiac recovery. We described a case of a patient with a pheochromocytoma, presenting with cardiac failure, hemoptysis, and pleural effusions. The rapid improvement of the patient’s cardiac and pulmonary conditions after the tumor removal may suggest the potential involvement of pheochromocytoma in these clinical manifestations. Conflict of interest statement The authors declare no conflict of interest. Author contributions Crouzet A and Morel J wrote the article. Other authors reviewed the article. Funding None. Ethical approval of studies and informed consent The study followed the principles of the Declaration of Helsinki as revised in 2013. This study was approved by the Ethics Committee “Terre d’Éthique” of the Universitary Hospital of Saint-Étienne (IRBN1782025/CHUSTE, 05/11/25), and written informed consent was obtained from the patient. Acknowledgements None.
Crouzet et al. (Mon,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: