Extra-adrenal pheochromocytoma presenting as inverse takotsubo-pattern cardiomyopathy treated with surgical resection

Abstract

Pheochromocytoma is a rare catecholamine-secreting tumour that is typically located in the adrenal medulla or along the sympathetic ganglia. The typical symptoms are episodic in nature and include tachycardia, sweating and headache. These tumours can present as transient, reversible cardiomyopathy similar to takotsubo cardiomyopathy (TCM). TCM is characterised by transient hypokinesis of the left ventricular apex and is typically induced by emotional stress. We describe the case of a 26-year-old woman with a medical history significant for headaches who presented initially to her family physician with nausea, vomiting, headache and hypertension. She was started on lisinopril 10 mg daily. One week later, she presented to the emergency department with substernal severe chest pressure. Her troponin level was elevated. Coronary angiogram showed normal coronary arteries and left ventriculogram showed inverse TCM pattern. Serum catecholamines were very elevated confirming pheochromocytoma. She was successfully treated with alpha-blockers followed by surgical resection.

Background

Pheochromocytoma is a rare catecholamine-secreting tumour that is typically located in the adrenal medulla or along the sympathetic ganglia. The typical symptoms are episodic in nature and include tachycardia, sweating and headache. These tumours have been reported to cause transient, reversible cardiomyopathy similar to takotsubo cardiomyopathy (TCM).¹ Typical TCM is characterised by a transient hypokinesis of the left ventricular (LV) apex and is typically induced by emotional stress. It commonly manifests in older women and tends to resolve within days to week. Coronary spasm, coronary microvascular dysfunction, catecholamine toxicity and myocarditis are suggested as potential contributing factors to development of TCM.²

Case presentation

We describe the case of a 26-year-old woman with a medical history significant for headaches who presented initially to her primary care physician with nausea, vomiting, headache and hypertension in August of 2017. She was started on lisinopril 10 mg daily with temporary resolution of her symptoms. She is a non-smoker and drinks alcohol socially. She denies any relevant family history. One week later, she reported substernal severe chest pain and was taken to an outside hospital emergency room. Her serum troponin level and creatinine were very elevated. An ECG showed 2 mm ST depressions in V3–V6. An urgent coronary angiogram showed normal coronary arteries with evidence of inverse TCM (ITCM) on left ventriculogram (figure 1). She was then transferred to our hospital where a right heart catheterisation showed normal filling pressures and cardiac index. She was found to be febrile on hospital transfer 39.6° C (103.3 °F) and was started on broad-spectrum antibiotics. Her respiratory status worsened and she did not respond to supplemental oxygen. She was intubated and placed on mechanical ventilation (figure 2). A transthoracic echocardiogram showed unusual pattern of regional LV systolic dysfunction with mild to moderately reduced left ventricular ejection fraction (LVEF) at 38%. All basal and mid LV segments appeared severely hypo kinetic with preservation of the apical segments consistent with ITCM. Due to intermittent left-sided abdominal pain, the patient underwent CT of abdomen/pelvis that showed a large mixed solid/cystic mass within the left retroperitoneal space arising from the left adrenal gland measuring 12.5×6.3×6 cm (figure 3). Endocrine surgery was consulted for evaluation of the adrenal mass. A 24-hour urinary cortisol, plasma renin, plasma aldosterone and 5-hydroxyindoleacetic acid were ordered in addition to serum and urine metanephrines with a strong suspicion for pheochromocytoma. The results of serum metanephrine and normetanephrine were abnormally high at 1.80 and >50, respectively. The patient was started on a slow titration of phenoxybenzamine (up to 60–100 mg daily) 10 days prior to surgery followed by metoprolol tartrate. She then underwent an open adrenalectomy. During surgery, she experienced some haemodynamic instability, with systolic blood pressure as high as 180 mm Hg and as low as 40 mm Hg, despite aggressive phenoxybenzamine therapy. A splenectomy was also performed due to bleeding of an unknown aetiology from the spleen. The patient tolerated the procedure well overall with minimal blood loss. Her antihypertensives were stopped postoperatively and did not need to be restarted prior to hospital discharge.

Figure 1.

Left ventriculogram showing inverse takotsubo-pattern cardiomyopathy.

Figure 2.

Chest X-ray showing pulmonary oedema with an endotracheal tube in good position. AP, anteroposterior.

Figure 3.

CT scan of the abdomen showing a large left retroperitoneal mass measuring 12.5×6.3×6 cm.

Outcome and follow-up

The patient is symptom free with normal blood pressure at 1-year outpatient follow-up. Her echocardiogram revealed normalisation of her ejection fraction with no wall motion abnormalities.

Discussion

Pheochromocytoma is a catecholamine-producing neuroendocrine tumour, most commonly associated with episodes of headaches, sweating and tachycardia. Excess catecholamines have been shown to cause reversible cardiomyopathy similar to stress-induced cardiomyopathy. Although the pathogenesis of pheochromocytoma-induced cardiomyopathy is not clear yet, it is proposed that catecholamines result in vasoconstriction and spasm of small arterioles and the metabolites cause direct toxic effects on the myocardium via free radical damage.³ It is of utmost importance to recognise pheochromocytoma as the cause of cardiomyopathy and early intervention is essential to improve mortality from acute pulmonary oedema.⁴ The first description of TCM was described in 88 patients in Japan, where patients had transient apical ballooning without significant coronary stenosis.⁵ A small proportion of similar TCM cases may be secondary to pheochromocytoma. There are reports of complete reversibility of the myocardial dysfunction in as early as 8 days after treatment with alpha-blockers. In another case report of cardiomyopathy induced by pheochromocytoma, the abnormally low ejection fraction normalised after medical treatment with captopril alone for 1 week followed by combination of captopril and phenoxybenzamine for another week.⁶ In our case, the patient was treated with phenoxybenzamine prior to surgical removal of the tumour with reversal of her symptoms.

Our case also highlights the pitfalls in not making the diagnosis of pheochromocytoma right away in a patient with non-ischaemic cardiomyopathy. Screening all patients with idiopathic cardiomyopathy for catecholamine excess is likely to lead to many false positive results and therefore is not a solution to this problem. It is important to establish a high index of suspicion for pheochromocytoma prior to further diagnostic workup. A high index of suspicion that increases the pretest probability of pheochromocytoma includes: younger age, genetic predisposition to pheochromocytoma, presence of adrenergic symptoms, blood pressure anomalies, TCM and radiological characteristics of pheochromocytoma.⁷ The ITCM makes this case one with a high index of suspicion for further workup of pheochromocytoma.

Learning points.

• Pheochromocytoma is a catecholamine-producing neuroendocrine tumour that can rarely present as inverse takotsubo cardiomyopathy.

• Aggressive blood pressure control preoperatively can be achieved with alpha-blockers such as phenoxybenzamine.

• Surgical resection of the neuroendocrine tumour at a specialised centre is key to achieve complete cure.