An unusual presentation of pheochromocytoma accompanied by catecholamine-induced cardiomyopathy

Abstract

Pheochromocytomas are catecholamine-secreting tumours arising from chromaffin cells in the adrenal medulla. They are rare, with an annual incidence in Europe of 0.2 per 100 000 people.¹ Diagnosis is challenging due to their rarity and non-specific symptoms. Half are discovered incidentally on computed tomography (CT) or magnetic resonance imaging (MRI). These tumours are histologically indistinguishable from extra-adrenal catecholamine-secreting neoplasms, commonly referred to as paragangliomas. The majority of catecholamine-secreting tumours occur sporadically; however, approximately 40% are associated with hereditary syndromes. Familial cases are more likely to present with bilateral pheochromocytomas or multifocal paragangliomas. All known familial syndromes associated with these tumours follow an autosomal dominant pattern of inheritance, including Von Hippel–Lindau (VHL) syndrome, multiple endocrine neoplasia type 2 (MEN2) and neurofibromatosis type 1 (NF1). The prevalence of pheochromocytoma in individuals with these syndromes is approximately 10%–20% for VHL, 50% for MEN2 and 2%–3% for NF1. Symptoms typically include at least two of the ‘classic triad’: headache, sweating and tachycardia.² Hypertension is the most frequent symptom, although 10% of patients are normotensive.¹ Rarely, pheochromocytoma is associated with cardiomyopathy attributed to catecholamine excess (catecholamine-induced cardiomyopathy, CICM) that is similar to stress-induced cardiomyopathy (also known as takotsubo syndrome, TTS).³ Twenty-nine percent of pheochromocytomas are malignant, but the commonest causes of mortality are complications related to high circulating levels of catecholamines, including stroke, acute renal failure, ischaemic heart disease, arrhythmias, heart failure and pulmonary oedema.^{4, 5} Definitive management is by resection, requiring careful surgical technique and anaesthesia management to avoid inducing catecholamine release and subsequent uncontrolled hypertension. Principles of management of paragangliomas are the same, but anatomical location can make resection challenging. The most typical paraganglioma sites are the carotid body, jugular bulb, middle ear and vagus nerve, and lower cranial nerve deficits are frequent complications of surgery.⁶ Genetic testing is recommended for all individuals diagnosed with catecholamine-secreting tumours and is typically performed following resection and histopathological confirmation. In cases where a hereditary syndrome is identified, genetic evaluation is also indicated for first-degree relatives to facilitate early detection and management.

A 39-year-old female patient presented to the emergency department with intractable vomiting and a 2-year history of recurrent shaking episodes with palpitations, tingling in her limbs and hot flushes. Migraine associated with nausea and vomiting often followed these episodes. Episodes had increased in frequency and now occurred daily, disrupting her life as a teacher. Despite review in a neurology clinic, no diagnosis had been established. In the emergency department, she was hypotensive, and bedside echocardiogram demonstrated global hypokinesia. Initial troponin was 543 ng/L, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 689 pmol/L and an electrocardiogram (ECG) demonstrated normal sinus rhythm with no ischaemic changes. She was admitted to intensive care for treatment with dobutamine and norepinephrine. Formal transthoracic echocardiogram showed left ventricle mid-segment hypokinesia and a left ventricular ejection fraction of 33%, in keeping with mid-ventricular variant TTS (see Figure 1). Coronary angiogram was normal.

Over 2 days on intensive care, the dobutamine and norepinephrine were weaned. The episodes of shaking, vomiting, and headache continued throughout the admission, and were associated with hypertension and ventricular ectopics. Once vasopressors and inotropes were discontinued, urine metanephrines were collected and were found to be grossly elevated. Phenoxybenzamine and bisoprolol were started for suspected pheochromocytoma. Prior to discharge, repeat echocardiogram showed normokinesis of all wall segments, and an improved ejection fraction of 62%. Outpatient CT confirmed a 55 mm adrenal pheochromocytoma, and laparoscopic adrenalectomy was performed 2 months later. Histology identified a clear resection margin and a low grading of adrenal pheochromocytoma and paraganglioma (GAPP) score, indicating a well differentiated type with a low risk of malignancy.⁷ Thirteen months post-adrenalectomy, the patient reported no further episodes of shaking and associated symptoms or migraine since surgery. Plasma metanephrines were normal at 6 months and CT at 1 year showed no evidence of tumour recurrence.

We describe an atypical presentation of pheochromocytoma, with CICM and hypotension. Pheochromocytoma diagnosis requires testing for metanephrines, but multiple drugs may interfere with these. CICM presents similarly to TTS, and several echocardiographic phenotypes have been described. More cases are required to determine the association of different phenotypes with different syndromes.

The authors have no conflicts of interests or external funding to disclose.