Transient cardiogenic shock during a crisis of pheochromocytoma triggered by high-dose exogenous corticosteroids

Abstract

We report a case of a 39-year-old woman who presented to the emergency department (ED) with symptoms of pharyngitis and fever. Diagnosed with streptococcal pharyngitis, she received antibiotics and dexamethasone, and was discharged. Within 24 h she returned to the ED with signs and symptoms of an acute coronary syndrome; she was thus given β-blockers. Her coronary angiogram was normal. She developed cardiogenic shock with an ejection fraction (EF) of 10% and apical ballooning on echocardiography. Her condition improved with optimal medical therapy. Subsequent testing weeks later confirmed the presence of a pheochromocytoma. Following prazosin and an adrenalectomy, all her antihypertensive medications were weaned and her EF normalised. We believe the high-dose exogenous corticosteroids triggered a pheochromocytoma crisis. The concomitant use of β-blockers without preceding α blockade resulted in cardiovascular collapse. Pheochromocytoma crisis must be included in the differential diagnosis of any dramatic haemodynamic collapse after administration of exogenous corticosteroid or β-blockers.

Background

Pheochromocytoma crisis (PC) is an endocrine emergency with a high mortality rate. Acute onset of severe congestive heart failure as a component of PC is an unusual presentation. Several case series of pheochromocytoma patients revealed an incidence of 10% of catecholamine cardiomyopathy with the most common presenting symptoms of new onset chest pain and dyspnoea. Exogenous glucocorticoids may trigger PC. The evidence linking exogenous glucocorticoids to PC is limited to single case reports with no controlled clinical studies demonstrating the relationship.

Case presentation

A 39-year-old woman with no significant medical history, a non-smoker and non-alcoholic, presented to the emergency department (ED) with sudden onset stabbing chest pain, diaphoresis and near syncope. She had been treated in the ED earlier that day for sore throat and fever. She was diagnosed with streptococcal pharyngitis, given oral antibiotics and dexamethasone (10 mg), and discharged. During the subsequent visit, she was afebrile, tachycardic and extremely hypertensive (211/120 mm Hg). Her physical examination revealed cervical lymphadenopathy and mild neck stiffness. Her urine drug screen was negative. Initial 12-lead ECG revealed ST elevation in the inferolateral leads (figure 1). Cardiac biomarkers were significantly elevated. Troponin-I 8.030 NG/ML (Ref <0.035 NG/ML), CK-MB 23.8 NG/ML (Ref <2.4 NG/ML).

Figure 1.

Admission ECG showing ST changes mimicking acute coronary syndrome.

ST-elevation myocardial infarction was diagnosed and medical management with prasugrel, aspirin, metoprolol, heparin and morphine was initiated. The patient was then transferred to our tertiary medical centre for emergent cardiac catheterisation. Her coronary angiogram was normal. During the angiogram, she developed acute respiratory failure requiring emergent intubation. Chest X-ray revealed pulmonary oedema. An immediate bedside echocardiography showed left ventricular (LV) ejection fraction of 10–15%, severe global hypokinesis of the mid-to-distal parts of the ventricle with better contractility of the basal segments (figure 2 and video 1). Soon later, the patient progressed to cardiogenic shock that necessitated the placement of an intra-aortic balloon pump.

Figure 2.

Admission echocardiography showing apical four-chamber view of the left ventricular (LV) at end-diastole (A), and end-systole (B). Note the apical ballooning in (B). Follow-up echocardiography after 4 weeks of medical therapy showing normalised LV function and resolution of apical ballooning (C) and (D).

Video 1

Echocardiography, apical four-chamber view showing severe global hypokinesis of the mid-to-distal parts of the ventricle.

Investigations

Cardiac MRI showed severely decreased LV function with akinesis affecting the mid-to-distal segments, suggestive of stress-induced cardiomyopathy with calculated ejection fraction (EF) of 29%. Normal pericardial thickness and normal delayed hyperenhancement of the myocardium and pericardium were seen (figure 3 and video 2).

Figure 3.

Cardiac MR apical four-chamber view showing akinesis in the mid-to-distal segments.

Video 2

Cardiac MR cine with apical four-chamber view showing severely decreased left ventricular function with akinesis in the mid-to-distal segments with calculated ejection fraction of 29%.

Differential diagnosis

The coronary angiogram findings ruled out acute coronary syndrome (ACS) as a cause of the patient's presentation. Her blood, sputum and cerebrospinal fluid cultures were all negative. However, she received empiric antibiotics for possible septic shock, given her recent streptococcal pharyngitis. Myopericarditis was high on the differential but it was ruled out by cardiac MRI. PC was not considered during her hospitalisation as she was lacking classical symptoms. Eventually, her presentation was thought to be multifactorial, related to hypertensive emergency and stress-induced cardiomyopathy progressing to cardiogenic shock and pulmonary oedema.

Treatment

The patient remained in the intensive care unit on milrinone, furosemide, nipride and nitroglycerine drips. Her blood pressure was controlled over the following 72 h but she continued to have sinus tachycardia for the first 7 days from admission. She was started on a combination of carvedilol, lisinopril, spironolactone and hydralazine, with appropriate haemodynamic response and normalisation of her vital signs. On day 10 she was discharged with a LifeVest and cardiology follow-up.

Outcome and follow-up

The patient's symptoms of palpitations and chest pain persisted necessitating an ED visit 1 week after discharge, which resulted in negative work up for ACS. At her cardiology follow-up appointment she reported recurrent spells of anxiety, palpitations and diaphoresis as well as poorly controlled blood pressure (BP) despite optimal medical therapy. Screening tests for pheochromocytoma were ordered and came back positive (table 1).

Table 1.

Laboratory results confirming the diagnosis of pheochromocytoma

TEST	Value	Normal range
Plasma-free metanephrine (MN)	48	≤57 pg/mL
Plasma-free normetanephrine (NMN)	538	≤148 pg/mL
Urine 24 h vanillylmandelic acid (VMA)	7.0	≤6 mg/24 h
Total, free (MN, NMN)	586	≤205 pg/mL
Normetanephrine 24 h urine	1461	52–310 µg/24 h
Metanephrine 24 h urine	358	19–140 µg/24 h
Chromogranin A	38.0	1.9–15 ng/mL
Total metanephrines, 24 h urine	1819	95–475 µg/24 h

CT of the abdomen and pelvis with contrast showed a 2.2 cm enhancing mass of the right adrenal gland (figure 4) consistent with pheochromocytoma. The patient was started on an α-1 antagonist (prazosin) and referred to surgery. Repeat echocardiography 4 weeks after prazosin showed normal LV size and systolic function, EF 50–55% (video 3).

Figure 4.

CT scan of the abdomen and pelvis with intravenous contrast revealing 2.2 cm enhancing mass of the right adrenal gland (arrows).

Video 3

Echocardiography, apical four-chamber view showing normal left ventricular size and systolic function.

The patient underwent uncomplicated right laparoscopic adrenalectomy. The pathology report revealed a pheochromocytoma confined within the adrenal gland capsule with no histological features of malignancy. Following surgery, all the patient's symptoms had resolved. Her postoperative catecholamine levels normalised. She was gradually weaned off her antihypertensive medications and is currently taking no prescription medications. Her BP level and LV function are normal. She is following up with endocrinology clinic on a yearly basis.

Discussion

Takotsubo cardiomyopathy is a reversible cardiomyopathy that was first described in 1990 in Japan by Sato et al. This unique syndrome presents with characteristic echocardiogram findings of transient apical and midventricular akinesis or dyskinesis, and hyperkinesis of the base in the absence of obstructive coronary artery disease.^{1 2} The shape of the ventricle at end systole resembles a Japanese fisherman's octopus pot (takotsubo) from which the syndrome derives its name.³ ECG changes include either ST-segment elevation and/or T wave inversion along with moderate elevation in cardiac troponin.^4–7 Severe physical and emotional stressors have precipitated this syndrome.^{1 3}

Reversible cardiomyopathy associated with pheochromocytoma is a recognised but uncommon entity. Before Sato coined the phrase ‘tako-tsubo’, an earlier report of reversible LV dysfunction associated with pheochromocytoma described the apical ballooning appearance, similarly seen in takotsubo, on echocardiogram.^{1 8} According to Mayo Clinic criteria, the presence of pheochromocytoma excludes the diagnosis of takotsubo syndrome.⁹ However, there is an increasing number of published case reports that describe takotsubo-like cardiomyopathy in the setting of pheochromocytoma.¹⁰ The pathophysiology of stress-induced cardiomyopathy and pheochromocytoma-induced cardiomyopathy is believed to be mediated by catecholamines.^5–7 Excessive epinephrine has a negatively inotropic effect via G-coupled protein changes. The G-coupled proteins that drive β₂-adrenoreceptor function switch from a positively inotropic Gs to negatively inotropic Gi.¹¹ The pathological changes to the apical myocardium are attributed to higher density of β₂-adrenoreceptors at this location.³ This process is called ‘stimulus trafficking’. Apical and mid-wall hypokinesis with resultant hypercontractile basal myocardium cause LV outflow tract obstruction.³

The prevalence of pheochromocytoma in the general population is estimated to be 0.3–1.9%.^{12 13} Its diverse manifestations can make the diagnosis difficult, especially when classic symptoms are absent.¹⁴

PC is considered an endocrine emergency with reported mortality as high as 85%.^15–17 Acute onset of severe congestive heart failure as a component of PC is an unusual presentation. Several case series of pheochromocytoma patients revealed an incidence of 10% of catecholamine-induced cardiomyopathy, with the most common presenting symptoms of new onset chest pain and dyspnoea.¹⁸ Surgical manipulation of the pheochromocytoma, general anaesthesia and trauma are known causes of acute hypertensive events in these patients.¹⁹ Additionally, exogenous glucocorticoids may trigger PC, as in our case. The evidence linking exogenous glucocorticoids to PC is limited to single case reports with no controlled clinical studies demonstrating the relationship clearly.¹⁵

Physiologically, glucocorticoids influence catecholamine production and potentiate its action on the heart and peripheral vessels. Glucocorticoids induce catecholamine biosynthetic enzymes such as tyrosine hydroxylasc, dopamine ß-hydroxylasc and phenylethanolamine N-methyltransferase.^{15 20} A series of 11 cases of PC related to administration of exogenous glucocorticoids demonstrated a time lag of 5–36 h between steroid administration and the development of symptoms. In 2 out of 11 patients, fatal outcomes were related to the administration of glucocorticoids. Eight patients developed either heart failure or cardiogenic shock and of these, two required mechanical cardiac assist devices to survive. Chest pain, severe hypertension and headache were the most common symptoms on presentation. Dexamethasone and βmethasone caused the most serious reactions.¹⁵

Initiation of β-blocker therapy without preceding α-blockade may precipitate haemodynamic collapse in patients with pheochromocytoma. Non-selective β blockade leads to the loss of β₂-receptor-mediated vasodilation compounded by unopposed α-receptor stimulation. Resultant vasoconstriction, arterial hypertension and increased afterload cause myocardial dysfunction and pulmonary oedema.¹⁴

After successful surgery, catecholamine excretion returns to normal in about 2 weeks and should be measured to ensure complete tumour removal. Catecholamine excretion should be assessed at the reappearance of suggestive symptoms or yearly if the patient remains asymptomatic.²¹

We believe our patient had an underlying pheochromocytoma that had never previously been diagnosed; the high dose of exogenous corticosteroids triggered the PC and the concomitant administration of β-blockers exacerbated the crisis, resulting in cardiovascular collapse and pulmonary oedema.

Learning points.

• Surges in catecholamine levels as a response to sudden shock, fright or danger, are believed to be responsible for the mechanism of takotsubo cardiomyopathy syndrome. However, a functioning adrenal tumour secreting excessive amounts of catecholamines can cause a similar entity called takotsubo-like or cathecolamine-induced cardiomyopathy.

• Pheochromocytoma crisis (PC) must be included in the differential diagnosis of any dramatic haemodynamic collapse after administration of exogenous corticosteroid or β-adrenergic blockade agents especially when echocardiography demonstrates findings similar to takotsubo cardiomyopathy.

• The measurement of blood and urinary catecholamines should be strongly considered in patients with cardiogenic shock in the absence of other causes of heart failure.

• Adequate α-adrenergic blockade and subsequent β-blockade followed by excision of the tumour is the standard of PC therapy. Recovery of the cardiomyopathy may take place either spontaneously or preoperatively during aggressive medical management.

• After surgical resection of benign pheochromocytoma, catecholamine levels should be assessed at the reappearance of suggestive symptoms or yearly if the patient remains asymptomatic.