Postpartum pheochromocytoma-induced takotsubo syndrome

Abstract

A postpartum patient with acute-onset dyspnoea and hypotention, associated with reduced left ventricular function requiring intensive blood pressure control, was initially misdiagnosed as having peripartum cardiomyopathy. Her clinical symptoms rapidly resolved. Echocardiography revealed reversible left ventricular dysfunction with apical ballooning and coronary angiography was normal. Based on these findings, we diagnosed takotsubo syndrome. Over the next two months, the patient experienced repeated bouts of elevated sympathetic activity. On workup, we found an adrenal mass and elevated urine metanephrines. After adrenalectomy, histology confirmed pheochromocytoma. Our patient had the rare diagnosis of postpartum pheochromocytoma-induced takotsubo syndrome.

Background

Acute-onset dyspnoea in a peripartum woman can be caused by a wide range of disorders, challenging both obstetricians and internists. Takotsubo syndrome, typically seen in postmenopausal women, is a rare but important aetiology of peripartum left heart failure. The more common differential diagnoses include peripartum cardiomyopathy, acute myocarditis, acute myocardial infarction or dilated cardiomyopathy. Pheochromocytoma during the pregnancy or peripartum is even more rare with an estimated prevalence of one in 50 000–54 000,¹ but essential to diagnose as it is life-threatening and requires specific blood pressure management. Catecholamine-induced cardiomyopathy occurrs in 8%–11% in patients with pheochromocytoma.² Takotsubo syndrome, a form of catecholamine-induced cardiomyopathy, accounts for 40%–46% of cases of acute catecholamine cardiomyopathy associated with pheochromocytoma.^{3 4} Few cases during the postpartum have been published in the literature.

Case presentation

A previously healthy 34-year-old woman presented with acute dyspnoea 2 hours after uneventful vaginal delivery of a full-term infant. She developed dyspnoea, nausea, vomiting and diaphoresis on micturition. She denied headache, chest pain or palpitations. She appeared ill, with a temperature of 36.4°C, blood pressure 90/60 mm Hg, pulse 120 per minute and respiratory rate 21 per minute. Oxygen saturation was 97% on 6 L of oxygen. There was no goitre or jugular venous distension. The heart examination revealed a regular tachycardia with no murmurs and lung auscultation was normal. Laboratory studies showed a troponin level of 1.14 ng/mL (reference range: 0–0.014 ng/mL). Serum electrolytes were normal. Her chest radiograph showed bilateral diffuse ground grass opacities. ECG showed sinus tachycardia with diffuse ST elevation on precordial leads (figure 1). Echocardiography demonstrated diffuse hypokinesis with apical ballooning. There was no right heart dysfunction, valvular disease or pericardial effusion (video 1, figure 2). Emergency coronary angiography showed normal coronary arteries. She responded to intravenous dobutamine and carperitide in the intensive care unit. On hospital day 2, repeat echocardiography showed improved left ventricular function. Over the next 2 months after discharge, she experienced bouts of non-exertional dyspnoea and palpitations with cold sweats. Echocardiography showed normal left ventricular function, but a cystic mass of the left adrenal gland was seen.

Figure 1.

ECG at presentation showed sinus tachycardia with diffuse ST elevation on precordial leads.

Video 1.

Download video file ^{(332.9KB, mp4)}

DOI: 10.1136/bcr-2020-240098.video01

Figure 2.

(A) Diastole, (B) systole.

Investigations

Contrasted tomography of the adrenal revealed a 10 cm cystic mass with a fluid collection(figure 3). In this patient, 24-hour urine total metanephrine measurement, a reliable screening test for pheochromocytoma,⁵ was 23.5 mg/day (reference range: 0.04–0.19 mg/day).

Figure 3.

CT scan of abdomen with contrast showed a 10 cm cystic mass with a fluid collection (arrow heads).

Differential diagnosis

The differential diagnosis of postpartum acute dyspnoea and ST-T changes on ECG includes pulmonary embolism, amniotic fluid embolism, spontaneous coronary artery dissection, myocardial infarction, peripartum cardiomyopathy and takotsubo syndrome. Reversible hypokinesis and apical ballooning on echocardiography associated with normal coronary angiography suggested takotsubo syndrome. Takotsubo syndrome and adrenal mass, associated with signs and symptoms of hyperadrenergic state, suggested pheochromocytoma.

Treatment

Doxazosin was started and a surgical left adrenalectomy was performed. Histology showed small nests of tumour cells surrounded by sustentacular cells, confirming the diagnosis of pheochromocytoma (figure 4).

Figure 4.

Pathology of left adrenal surgical specimen showed small nests of tumour cells surrounded by sustentacular cells.

Outcome and follow-up

The diagnosis of takotsubo syndrome with pheochromocytoma was made. Postoperative course was uncomplicated. At the 1-year follow-up visit, she remained symptom-free. Repeated history taking confirmed no family history of pheochromocytoma and paraganglioma. Germline mutation genetic testing was negative.

Discussion

A previously healthy 34-year-old woman presented with postpartum cardiogenic shock with reduced left ventricular function which was ultimately diagnosed as pheochromocytoma-induced takotsubo syndrome. This case posed challenges in two aspects: postpartum takotsubo syndrome and subsequent recurrent sympathetic activation resulting from pheochromocytoma. There is scarce literature describing how these two critical conditions can be linked in the peripartum period.

Takotsubo syndrome affects mainly elderly women and is often triggered by an emotional exposure or a physical stress.⁶ Takotsubo syndrome may manifest with chest pain, symptoms of heart failure and ST-T changes which mimic acute coronary syndrome, accompanied by focal left ventricular dysfunction and abnormal cardiac enzymes.² It is difficult to differentiate peripartum cardiomyopathy and takotsubo syndrome in pregnancy, as the latter often develops during peripartum.⁷

In this case, postpartum takotsubo syndrome was initially suspected. However, recurrent symptoms suggestive of sympathetic activation and the incidental finding of an adrenal mass on imaging prompted us to evaluate for pheochromocytoma. Imaging and pathology of the pheochromocytoma showed intratumoural haemorrhage, which may have intensified the catecholamine surge.³

The incidence of pheochromocytoma is about 0.8 per 100 000 person-years.⁸ Pheochromocytoma can occur at any age, but it is most common in the fourth to fifth decade and is equally common in men and women.⁹ Pheochromocytoma is very rare in pregnant women, with an estimated prevalence of 1 in 50 000–54 000.¹ Episodic headache, sweating and tachycardia are the classic triad of symptoms.¹⁰ Hypertension can be either persistent or paroxysmal. The clinical features of pheochromocytoma are associated with catecholamine secretion. During the pregnancy, a surge of catecholamines can be caused by increased abdominal pressure, uterine contraction and delivery. Peripartum pheochromocytoma is difficult to diagnose because its clinical picture mimics that of pre-eclampsia.¹¹ Maternal and fetal mortality from pheochromocytoma is high in pregnancies, especially when not diagnosed until childbirth, and is reported to be 8% and 17%, respectively.¹²

Three patterns of cardiomyopathy in pheochromocytoma have been reported: takotsubo syndrome, dilated cardiomyopathy and hypertrophic cardiomyopathy.² Patients with takotsubo syndrome associated with pheochromocytoma are often younger and lack typical symptoms of pheochromocytoma, such as headache, palpitations, diaphoresis and hypertension. Cardiogenic shock is a presenting sign in 20% of patients with takotsubo syndrome and pheochromocytoma.¹³

Management of takotsubo syndrome in pheochromocytoma requires control of blood pressure with alpha-adrenergic blockers, followed by beta-adrenergic receptor blockers and surgical removal of the tumour. In cases of refractory hypotension with acute heart failure, vasopressors may be ineffective and mechanical circulatory support may be needed.²

This case highlightes the importance of broadening the differential diagnosis for reversible postpartum cardiogenic shock by including takotsubo syndrome and pheochromocytoma, as they require different management from other cardiomyopathies and are associated with a high risk of death.

Learning points.

• Takotsubo syndrome is important in the differential diagnosis of peripartum cardiomyopathy.

• Peripartum pheochromocytoma is difficult to diagnose as it mimics pre-eclampsia.

• Cardiogenic shock can be an intial presentation of pheochromocytoma-induced takotsubo syndrome.