E-Poster Presentation 63rd Endocrine Society of Australia Annual Scientific Meeting 2020

Case report

A 40-year-old man (MO) was admitted to the hospital with severe shortness of breath after experiencing several days of upper respiratory tract symptoms. He did not have other past medical history and was well and active. MO was a cigarette smoker and occasionally smoked marijuana which helped to manage his anxiety.

On arrival to the emergency department, MO was hypoxic with low oxygen saturations (60%), tachycardia (pulse 120 regular) with a blood pressure of 160/90mmHg.The clinical examination revealed respiratory distress, reduced air entry to lungs without hepato-splenomegaly or pitting oedema consistent with acute cardiac failure. The electrocardiogram showed sinus tachycardia with ST elevation in anterolateral leads (image 1). An emergency cardiac echocardiogram showed globally reduced left ventricular contractility with an ejection fraction of 10%. The initial troponin was 15000. The working diagnosis was a cardiogenic shock from myopericarditis.MO was admitted to the ICU for close observation and management.

A dobutamine infusion was administered to improve cardiac contractility. The patient was also treated with broad-spectrum antibiotics for a possible respiratory infection. A viral swab was positive for picornavirus, which raised the possibility of a viral myopericarditis. MO had a fast recovery and was soon transferred to a non-acute ward.

The repeat echocardiogram showed improved left ventricular contractility with an improved ejection fraction of 40%. MO was started on enalapril and bisoprolol for heart failure. His blood pressure remained elevated, and plasma catecholamines were requested as part of secondary screening which were elevated (noradrenalin 49.9nmol/L {ref 0.1 - 6.3}, adrenaline 24.9nmol/L {ref 0.1 - 6.3}, normetanephrine 11.748nmol/L {ref<0.670}, metanephrine 14.20nmol/L {ref< 0.447} (chart 1 and table 1). MO remained well, and the blood pressure normalised without further intervention. He was discharged following repeat collection of urine and plasma for catecholamines (results were pending) with an outpatient adrenal CT scan and endocrine follow-up.

MO remained asymptomatic with normal clinic blood pressure. The repeat catecholamines were elevated. The abdominal CT scan showed a left-sided adrenal mass (image 2).MO was readmitted for staging and preparation for surgery. A 68Ga-DOTATATE PET/CT showed a large dotatate avid left adrenal lesion consistent with pheochromocytoma. No extra-adrenal lesions were identified (image 3).

The case was discussed in the MDT meeting, and a decision was made for urgent surgery. The patient was commenced on phenoxybenzamine and high salt intake. The enalapril was discontinued. The patient underwent laparoscopic adrenalectomy eight weeks post initial presentation. The histology confirmed a 48 mm pheochromocytoma.

The patient is being followed up in the endocrinology outpatient clinic and is doing well. The post-surgery echocardiogram showed full recovery of cardiac function with an ejection fraction of 40%. The repeat catecholamines were normal, and the screening for genes associated with pheochromocytoma was (RET, SDHG, VHL) negative.

Discussion

Significant stress, such as burns, sepsis, surgery, or trauma, can raise plasma catecholamine levels. Following stress, the pituitary-adrenal axis and sympathetic division of the autonomic nervous system are activated, which promotes exocytosis of catecholamine-filled vesicles to plasma⁵.

Catecholamines have multisystem actions. Their actions on the cardiovascular system regulate blood pressure by contracting the smooth muscle in the vasculature (via alpha-1 receptors) and enhance contractility of cardiac muscle (via beta-1 receptors)¹. As a result, catecholamines are implicated in a multitude of diseases, including cardiogenic and non-cardiogenic shock. The levels of a physiological rise in plasma catecholamine during stress have not been quantified, and no studies are available comparing the difference between physiological and pathological release.

Most patients with a pheochromocytoma will present with clinical symptoms of diaphoresis, palpitations, and headaches, but our patient did not have any such symptoms². The only relevant symptom was intermittent anxiety experienced for the past four months which settled with smoking marijuana. Also, the patient had a full recovery and remained asymptomatic following the initial admission and maintained a normal blood pressure which raised the question if it was, in fact, the stress from cardiac disease and assay interference of dobutamine infusion was responsible to the initial rise of the catecholamines. Studies show, heart failure with dilated cardiomyopathy can increase plasma catecholamines more than ten folds^{7, 8}. However, measuring plasma catecholamines in patients with cardiogenic shock is challenging since exogenous catecholamines are frequently used in the treatment⁹.

Catecholamine induced cardiomyopathy in the setting of pheochromocytoma is an unusual clinical entity. The overwhelming effect of catecholamines results in vasoconstriction of small arterioles and also cause a direct toxic effect on the myocardium. The majority of patients with pheochromocytoma have other associated symptoms of raised catecholamines³.

The key to management of catecholamine-induced cardiomyopathy associated with pheochromocytoma is early intervention with surgical excision, which can result in complete reversibility of the myocardial dysfunction⁶.There are case reports of the use of phosphodiesterase 3 inhibitors while waiting for surgery (ref). Such inhibitors enhance peripheral vasodilatation and cardiac contractility by increasing cyclic Adenosine Monophosphate (cAMP) activity and thereby increasing calcium influx into the cardiac sarcoplasmic reticulum⁴.

This case highlights the highly variable presentation of pheochromocytoma and the importance of a broad understanding of possible presentations since it is imperative to diagnose and intervene early.

Take-home points

• Plasma catecholamines can rise following significant stress and can be affected by many medications.
• Pheochromocytoma can present as catecholamine’s induced cardiac myopathy without any other symptoms in an otherwise well patient.
• Early intervention with surgery can rapidly and completely reverse catecholamine-induced cardiac disease.