Phaeochromocytoma is a secreting neuroectodermic tumour of which 85% are located in the suprarenal area. The commonest manifestations are paroxysmal or sustained arterial hypertension associated with or without the conventional triad of headaches, sweating and palpitations. Many cases are described in the literature where the symptoms may be deceptive, diverse, and the diagnosis often delayed [1–30]. Diagnosis can be made when complications occur, e.g. when necrosis of the tumour occurs [5,6,10,13,19,21]. We describe a case of an undetected adrenal phaeochromocytoma mimicking acute pyelonephritis at the stage of necrosis.
A 30-year-old man was admitted to the urological surgical unit with suspected acute right pyelonephritis. He gave a 9-year history of arterial hypertension, controlled with perendopril and verapamil. He had had a short admission to the medical emergency unit 6 years previously for severe headache and an influenza-like syndrome. The presenting symptoms began the day before his admission to hospital. He developed abdominal pain, vomiting, polyuria, dysuria and a fever. Clinical examination at that time revealed tenderness in the right lumbar fossa, profuse sweating, and a pyrexia of 37.8°C. Arterial pressure was 180/90 mmHg and heart rate pulse was 96 beats min–1. He had discontinued his antihypertensive medication during the previous 36 h. At admission, the clinical picture persisted with increased tachycardia and some crepitations were heard at the lung bases. The patient was conscious and fairly restless. Arterial pressure was 120/65 mmHg although no antihypertensive medication had been administered. There was moderate dypsnoea without cyanosis. The electrocardiogram revealed a sinus tachycardia (180 beats min–1) but no evidence of myocardial ischaemia or left ventricular hypertophy. Urinanalysis revealed neither leukocytes nor nitrites. The patient’s respiratory status deteriorated rapidly with severely disturbed arterial blood–gases (PCO2=3.9 kPa; PO2=5.8 kPa breathing oxygen 8 L min–1 by facemask). The patient was transferred to the intensive care unit where assisted ventilation of the lungs was initiated. Persistant tachycardia required treatment with amiodarone; β-adrenoceptor blocking agents were not used because of haemodynamic instability. Shortly afterwards arterial pressure decreased to 70/45 mmHg and central venous pressure was 3.5 cmH2O. A diagnosis of septic shock associated with urinary tract infection was made. The patient was given 500 mL of hydroxyethyl starch and inotropic support infusions were started (dobutamine 6 μg kg–1 min–1 and norepinephrine 0.08 μg kg–1 min–1). Extensive purple mottling of the skin and a generalized vasoconstriction developed. Biochemical investigations were compatible with an inflammatory syndrome and also demonstrated a metabolic acidosis, severe hypoxia, acute renal failure and raised cardiac enzymes (Table 1). Chest radiography showed a diffuse pulmonary infiltration (‘white lung’). Blood–gas analysis (FiO2/PaO2 < 70) and radiological findings confirmed an acute adult respiratory distress syndrome (ARDS) which could not be improved despite the administration of inhaled nitric oxide (PCO2= 6.1 kPa, PO2=7.6 kPa with 15 ppm nitric oxide).
Abdominal ultrasound undertaken to confirm acute pyelonephritis surprisingly revealed a right necrotic-centred suprarenal mass of 8-cm diameter. There were no signs of gut or urinary pathology. A diagnosis of phaeochromocytoma was made. Anuria prevented the titration of catecholaminergic urinary derivatives. Transoesophageal echocardiography was unavailable. Transthoracic echocardiography revealed septal hypokinaesia without underlying cardiomyopathy or any suggestion of infectious myocarditis. Proper assessment of ejection fraction was hampered by the tachycardia. During this examination the patient sustained a cardiac arrest (ventricular fibrillation); defibrillation was ineffective, asystole developed, and the patient died within 2 h after his admission to the intensive care unit (ICU). The rapid deterioration and the priority given to ultrasound examination prevented right cardiac catheterization. A post-mortem examination confirmed the existence of a right necrotic-centred adrenal phaeochromocytoma (Fig. 1). The histological examination of the myocardial samples showed an inflammatory reaction of the interstitium with a predominance of mast cells and eosinophils associated with a moderate impairment of the myocardial fibres (Figs 2 and 3). The same, but less numerous, inflammatory elements were detected in the lung samples. Extensive oedema of the pulmonary alveoli was associated with centres of haemorrhagic suffusion and a considerable congestion of the septal vessels.
Phaeochromocytoma is most often detected during routine investigation of arterial hypertension . The symptoms can be deceptive and presentation can be atypical (Table 2). Thus, some phaeochromocytoma that had previously remained occult could present as acute, life-threatening cardiovascular failure. Emergency presenting features include acute heart failure, myocardial infarct, abdominal emergency due to haemorrhagic tumour rupture, pulmonary oedema or intraoperative cardiac dysrhythmia [2,6,7,14,15,20]. Occasionally, the diagnosis is established only after death .
In the present case, the patient had been treated for 9 years for hypertension. His previous history reveals few symptoms and limited interventions by a few physicians. An abdominal ultrasound (which is an easy and low-cost procedure) would have been sufficient to demonstrate the tumour in this patient and allow its surgical removal in optimal conditions with a reduced operative mortality risk .
The cardiovascular manifestations indicate the severity of the phaeochromocytoma. Arterial hypertension results from the stimulation of the β- 1 adrenergic receptors of the smooth vascular muscle and can lead to hypertensive cardiomyopathy. Regardless of hypertension, a sustained catecholaminergic stimulation can cause a ‘catecholamine-induced myocarditis’. This has the feature of a dilated cardiomyopathy with multifocal necrosis and intracellular excess of calcium  that can lead to acute cardiac failure and improves with removal of the tumour [2,8,30]. In the present case, neither the absence of dilated cardiac cavities and subnormal ejection fraction assessed by transthoracic echocardiography, nor the autopsy findings suggested a pre-existing cardiomyopathy. Unfortunately, the absence of haemodynamic data – that might have been obtained from right cardiac catheterization – made it difficult to determine the physiopathological pattern of the cardiorespiratory failure. The pseudo clinical septic shock considered would probably have been reviewed in favour of cardiogenic shock [13,14]. The necrosis of the tumour explains the pseudo-infectious clinical picture (pain, fever, chills) and the biochemical results (polymorpholeukocytosis, rise of C-reactive proteins, hyperfibrinogenemia). Its severity indicates a very bad prognosis [6,15,16,30]. Tumour necrosis and tumour manipulation by palpation are known to induce a massive release of catecholamines, thus increasing the incidence of dysrhythmias which led to the patient’s death [7,16,20]. Moreover, tachycardia entails a significant fall in the venous return, which potentates heart failure and leads to an abrupt rise in the myocardial oxygen demand. Dysrhythmia may have been exacerbated by severe hypoxia and myocardial vasoconstriction. A spasm of the small intramyocardial vessels after the massive release of catecholamines might explain the absence of myocardial ischaemia on electrocardiography and histological findings from myocardial samples . The predominance of mast cells and eosinophils in the area of the interstitial oedema indicates a vascular origin for the inflammatory reaction. The normally inhibiting activity of β- 2 adrenoceptor agonists on the mast cell degranulation is probably reduced by the prolonged exposure to catecholamines, thus inducing a desensitization of the receptors [32,33]. Moreover, β- 1 adrenergic receptor stimulation has been shown to induce a mast cell degranulation that leads to marked increase of vascular permeability [34,35]. In other respects, hypoxia generates the liberation of vasoconstrictive substances by the endothelial cells. Likewise, endothelin is released after the activation of the endothelial receptors by catecholamines and is increased in some instances of cardiovascular failure . All these mechanisms may have generated a vasospasm of the microcirculation, particularly the myocardial one, that originated an ‘acute catecholamine myocarditis’. Nevertheless, an abrupt rise in afterload, after a hypertensive peak due to the catecholamine release, might also explain the occurrence of pulmonary oedema. Although data preceding the cardiopulmonary signs do not favour this hypothesis, the intermittent measurement of arterial pressure made it possible to miss a diagnosis of paroxysmal hypertension. Most probably the pulmonary oedema resulted from a pulmonary vasospasm induced by the catecholamine release due to tumour necrosis. The intense sympathetic stimulation generates an opening of the pulmonary capillaries and an alveolar flooding causing a so-called neurogenic pulmonary oedema [2,29].
Early surgery remains the single definitive therapy able to stop the lesional process due to the chronic exposure to catecholamines . The risk of surgery is reduced by preventive and curative medical treatment that includes α- or β-adrenoceptor blocking drugs, calcium inhibitors or sodium nitroprusside. These agents make it possible to control hypertension and the cardiac manifestations generated by the phaeochromocytoma during the perioperative period . In fortuitously detected cases the problem is more delicate. Thus, in our patient cardiogenic shock with multiorgan failure and ARDS resulted in a rapidly deteriorating prognosis: the patient’s state was severely compromised within 2 h of admission by the onset of fatal dysrhythmia. Surgery could, therefore, not be considered. In the context of controlled multiorgan failure, a surgical intervention was planned 36 h after admission at the earliest . Some patients could, therefore, benefit from surgical treatment under cover of massive doses of inotropic drugs. In other cases, the insertion of an intra-aortic balloon pump was necessary to optimize surgical treatment, especially when the massive release of catecholamines generates a receptor desensitization that reduces the effectiveness of the vasopressive treatment . Unfortunately, the rapid deterioration of the patient also prevented this alternative approach.
Although the surgical and perioperative management of cases of phaeochromocytoma has made undeniable headway, patients presenting with acute cardiovascular complications still have a high mortality rate. Fatal outcome is more likely when there is underlying myocardial impairment or tumour necrosis that results in intense catecholamine release and tissue hypoxemia. Even though the management of a phaeochromocytoma presents extremely high morbidity and mortality criteria when acute complications occur, curative surgical treatment must be proposed. However, this can only be considered after haemodynamic control with inotropic drugs, monitoring by pulmonary artery flotation catheter and/or the insertion of an intra-aortic balloon pump. An early diagnosis is of cardinal significance to improve the therapeutic management of patients with phaeochromocytoma. Therefore, arterial hypertension of the young subject must be thoroughly investigated. Nevertheless, atypical presentations of phaeochromocytoma will continue to confront clinicians with difficulties.
We thank Professor J. M. Vetter, Institut d’Anatomie Pathologique, Hôpitaux Universitaires de Strasbourg, for providing histological data and photographs.
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