Case of pheochromocytoma mimicking MINOCA

Abstract

We present a 52-year-old woman who was admitted to the emergency department with a short history of palpitations, sweating and nausea. An electrocardiogram (ECG) that was performed suggested inferolateral ischaemia with a significant troponin rise. The patient underwent an invasive coronary angiogram that showed mild non-obstructive coronary disease. She was thus given a provisional diagnosis of myocardial infarction with non-obstructive arteries (MINOCA), treated as an acute coronary syndrome (ACS) and subsequently discharged home. The patient represented within 72 hours with a recurrence of symptoms and a further troponin rise. While on the ward severe recurrent orthostatic hypertensive episodes were noted. Further investigations revealed increased urinary and plasma metanephrines, increased plasma catecholamines and imaging revealed a left adrenal 5.7 cm mass, demonstrating probable pheochromocytoma. The patient was treated with curative surgery. This case highlights the importance of thorough history-taking in patients with atypical symptoms for acute coronary syndrome and diagnosed with MINOCA.

Background

Pheochromocytomas are rare tumours of the adrenal gland that arise from chromaffin cells in the adrenal medulla. Patients classically present with palpitations, sweating, headaches and paroxysmal hypertension. Pheochromocytomas are estimated to account for up to 0.1% of new cases of hypertension per year.¹ However, the non-specific and heterogeneity of symptoms may lead to a delay in the diagnosis.

The biochemical diagnosis of pheochromocytoma is suggested by elevated measurements of urine metanephrines and total plasma metanephrines. Further abdominal imaging is required in order to localise the tumour. Such imaging studies include CT, MRI and positron emission tomography (PET). Imaging should be done only after the biochemical confirmation of the pheochromocytoma and exlcusion of potential false positives.²

Pheochromocytomas exert their effect by secreting predominantly the hormones epinephrine and norepinephrine, which stimulate adrenergic receptors, including those within the cardiovascular system. Patients with pheochromocytoma can present with a number of cardiovascular complications such as arrhythmia, hypotension, shock, myocardial ischaemia, cardiomyopathy, aortic dissection, transient ischaemic attack and stroke. These complications make these tumours potentially lethal if not diagnosed and treated appropriately.

In this case report, we present a case of pheochromocytoma mimicking a myocardial infarction (MI) with non-obstructive arteries (MINOCA). The diagnosis of a MINOCA requires (1) the diagnosis of MI; (2) evidence of non-obstructive coronary arteries on invasive coronary angiography) and (3) no clinically overt specific cause for the acute presentation.

It is, thus, important to investigate and identify the underlying cause of a MINOCA, particularly in the context of an atypical history for acute coronary syndrome (ACS).

Case presentation

A 52-year-old woman presented to the emergency department with a short history of palpitations, sweating and nausea. She was referred by the general practitioner after a significant troponin rise in her bloods. She was previously diagnosed with essential hypertension and type II diabetes mellitus and was taking bisoprolol, amlodipine and metformin accordingly. She had also been seen in the emergency department a year ago with similar symptoms and had been investigated with ambulatory Holter monitoring and thyroid function tests with no abnormalities found. No family history of cardiovascular disease was noted. She was otherwise generally fit and well, a non-smoker and teetotal.

On admission, physical examination of the cardiovascular and respiratory systems was unremarkable, except for a resting blood pressure (BP) of 182/62 mm Hg. The index 12-lead ECG that was performed showed widespread ST/T changes in II, III, aVF (augmented Vector Foot), and V4-V6 leads (figure 1). Initial blood tests were normal except a significantly raised high-sensitivity troponin I with serial values of 450 ng/L and 103 ng/L (gender-based normal <15 ng/L). Therefore, she was diagnosed with a suspected ACS and was commenced on treatment as per local hospital guidelines. An inpatient invasive coronary angiogram that was performed within 24 hours, showed non-obstructed coronary arteries and only mild diffuse coronary disease (figure 2). Inpatient echocardiography showed moderate concentric LV hypertrophy with normal systolic function, no regional wall motion abnormality and no valvular disease (figure 3). The provisional clinical diagnosis was MINOCA and the patient was discharged home with secondary prevention medication for ACS and optimised antihypertensive treatment including amlodipine 5 mg, bisoprolol 5 mg and ramipril 5 mg once daily.

Figure 1.

12-lead ECGs (upper and lower panels) demonstrating T wave inversion in leads II, III, aVF, V4–V6 on index admission (upper panel) and showing resolved ischaemia following the second admission (lower panel). aVR, augmented Vector Right; aVL, augmented Vector Left; aVF, augmented Vector Foot.

Figure 2.

Still frames from the invasive coronary angiogram (left and right panels) showing mild diffuse coronary disease but non-obstructed coronary arteries. LCA, left coronary artery; RCA, right coronary artery.

Figure 3.

Still frame of a transthoracic echocardiogram, parasternal long axis view, demonstrating moderate concentric LV hypertrophy. LV, left ventricle.

Forty-eight hours following discharge, the patient represented to the emergency department with recurrent symptoms of palpitations, sweating, dizziness and vomiting. Clinical examination including observations, blood investigations and a series of electrocardiograms were normal (figure 1). However, a new troponin rise of 372 ng/L was noted in comparison to a final level of 103 ng/L recorded at the end of her index admission. The patient was admitted for further investigations.

Investigations

During her hospital stay, it was noted that the patient would become symptomatic with palpitations, sweating and nausea whenever standing up and going to the toilet. These were associated with an increase in blood pressure, and transient readings up to 283/153 mm Hg. The above episodes in addition to the history of recurrent palpitations in the community, raised the clinical suspicion of an underlying pheochromocytoma. Further investigations revealed raised plasma and urinary catecholamines. Plasma metadrenaline and normetadrenaline were also elevated at 29 798 pmol/L (normal value <510 pmol/L) and 30 835 pmol/L (normal value <1180 pmol/L), respectively. CT demonstrated a unilateral left suprarenal 5.8×5.6 cm heterogeneous well-defined mass arising from the lateral limb of the left adrenal gland. MRI confirmed a left adrenal 5.7 cm well-defined isolated heterogenous mass with intracellular fat characteristic of adrenal adenoma (figure 4). No focal invasion, enlarged locoregional lymph nodes or metastasis were found. Renal artery stenosis was also excluded. The above in the context of positive urine and plasma catecholamines is consistent with a diagnosis of pheochromocytoma.

Figure 4.

Abdominal MRI transverse (upper and lower left panels) and coronal slices (upper and lower right panels) demonstrating a left adrenal mass (highlighted with red false colour) measuring 5.7 cm.

Treatment

She was medically stabilised with improved symptoms using the non-competitive alpha-adrenergic and beta-adrenergic receptor blockers (phenoxybenzamine and propranolol, respectively) and was referred for curative surgery.

Outcome and follow-up

The patient underwent a left laparoscopic adrenalectomy with histopathological confirmation of the diagnosis, and both the operation and postoperative course were uncomplicated. The patient recovered fully with no clinical or biochemical sequelae. She returned back to normal activities 5 weeks after the surgery and remains under the clinical follow-up.

Discussion

MINOCA is clinically defined by the presence of the universal acute MI criteria, absence of obstructive coronary artery disease (defined as ≥50% stenosis on invasive angiography), and no cause for the clinical presentation at the time of angiography.³

MINOCA is currently a working diagnosis that requires the identification of an underlying cause.⁴ Potential coronary causes include type 1 MI or ACS due to coronary spasm, coronary microvascular dysfunction, plaque erosion, coronary embolus and spontaneous coronary dissection. Myocardial disorders, such as myocarditis, takotsubo cardiomyopathy and other cardiomyopathies, non-cardiac causes such as pulmonary embolism and renal impairment and other causes of type 2 MI, are included in the current differential of MINOCA.³

Type 2 MI is an umbrella term used to describe the troponin release due to myocardial cell injury secondary to supply-demand mismatch, in this case caused by sudden excessive secretion of catecholamines by the pheochromocytoma in the context of left ventricular hypertrophy.⁵

Pheochromocytomas are not listed currently as one of the causes of MINOCA. There are, however, several cases of underlying pheochromocytoma associated with MINOCA noted in the literature.^6–9 This condition should, therefore, be included in the broad differential diagnosis for MINOCA and is an important diagnosis as it is associated with cardiomyopathy, arrhythmia and sudden cardiac death.

Imaging is fundamental to the final diagnosis and management of neuroendocrine tumours such as pheochromocytomas and paragangliomas. The former originates from the adrenal medulla, the latter from the sympathetic and parasympathetic nerves. Following the arousal of clinical suspicion and positive biochemical tests, anatomical imaging is first used to detect and locate pheochromocytomas.¹⁰ Abdominal sonography, CT and MRI can be used, the latter two cross-sectional techniques being the most sensitive. CT is the most frequent imaging method employed, as it can detect adrenal pheochromocytomas larger than 5–10 mm with sensitivity >95% and it is widely available.¹¹ MRI is more sensitive and allows for superior soft-tissue characterisation as well as having the benefits of being free of ionising radiation and can be used in cases where there is a history of adverse reaction to iodinated contrast medium.¹¹ After anatomical imaging, confirmation of the source of the increased production of catecholamines and detection of extra-adrenal tumours, metastases and recurrent disease can be obtained with functional imaging.¹⁰ This carries the advantage of confirming the pathophysiological basis of disease and performing whole body imaging. I¹²³-meta-iodobenzylguanidine scintigraphy is the most frequent technique used and is considered the ‘gold standard’ with high specificity and sensitivity, relatively low exposure to ionising radiation, wide availability and low cost. PET using isotopes such as 18F-FDG (fluorodeoxyglucose 18F)or F-DOPA (fluorodopa) and somatostatin receptor imaging have even greater sensitivity compared with MIBG for metastases and are alternative methods of functional imaging than can be employed where high clinical and biochemical suspicion remains and the MIBG is negative.¹¹

Our case illustrates that there is potential for pheochromocytoma crises to mimic an acute type 2 MI and should be considered in the presence of unexplained or atypical findings for ACS. The presence of pre-existing essential hypertension does not exclude the possibility of concomitant secondary hypertension particularly in the context of paroxysmal hypertension. The key to diagnosis, is a high index of clinical suspicion. In this way patients may be diagnosed earlier.

Learning points.

• Pheochromocytomas are rare tumours which present with a variety of non-specific symptoms which may mislead the clinician and delay the diagnosis.

• Patients who present with troponin rise and unexplained myocardial infarction with non-obstructive arteries (MINOCA) should be investigated in depth for an underlying diagnosis, based on the clinical context.

• Pheochromocytoma crisis should be included in the differential diagnosis for MINOCA.

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