Incidental detection of pheochromocytoma during workup for symptomatic aortic stenosis: A case report and management discussion

Abstract

Pheochromocytoma patients with high levels of circulating catecholamines are at risk of cardiovascular complications related to hypertensive emergencies and subsequent organ damage. A patient with concomitant aortic stenosis and pheochromocytoma has compounded risk of cardiovascular complications, especially during surgery, which complicates medical decision-making. We report a patient with Turner syndrome and congenital heart defects (CHDs) who was incidentally discovered to have a pheochromocytoma during workup of symptomatic severe bioprosthetic aortic stenosis. Management included laparoscopic adrenalectomy followed by Transcatheter Aortic Valve Replacement (TAVR). We describe considerations for multidisciplinary management in this complex clinical case.

1. Introduction

Pheochromocytoma is rare, with a prevalence of 1:2500–6500 people. Patients with concomitant pheochromocytoma and aortic valve stenosis are even less common and present challenging diagnostic and management dilemmas. While comprehensive guidelines exist for the management of pheochromocytoma,¹ they do not provide recommendations tailored to patients with aortic stenosis.² Preoperative alpha blockade decreases perioperative mortality by preventing excess catecholamine production and increasing cardiovascular recovery.³ However, the presence of aortic stenosis poses a problem due to decreased afterload and bradycardia during alpha blockade. This complication could result in decreased cardiac output and myocardial infarction, making preoperative medical management complex.²

The order in which to manage pheochromocytoma and symptomatic aortic stenosis is the primary clinical challenge. Performing adrenalectomy prior to AVR can result in a catecholamine surge and hemodynamic fluctuation, compounding the cardiovascular risk of the existing aortic stenosis.⁴ Performing AVR with a known pheochromocytoma in situ could result in a catastrophic catecholamine surge during complex cardiac surgery. Unfortunately, high level data to guide this decision-making are scarce.² Case studies have reported successful laparoscopic adrenalectomy in patients with unrepaired aortic stenosis, as well as instances of successful AVR before adrenalectomy.^2,3,4,5 In one case, symptomatic aortic stenosis resolved following adrenalectomy and no longer required aortic valve replacement.³

To our knowledge, we report the first case of a Turner syndrome patient with concomitant symptomatic bioprosthetic aortic stenosis and pheochromocytoma managed with laparoscopic adrenalectomy followed by TAVR.

2. Case presentation

A 66-year-old female was evaluated for dyspnea on exertion (DOE), episodic palpitations, and diaphoresis. Her past medical history was significant for Turner syndrome with congenital bicuspid aortic valve and aortic stenosis status post prosthetic aortic valve replacement 12 years prior. In addition, she had a congenital coarctation of the aorta status post stenting as an infant, persistent atrial fibrillation, coronary artery disease status post percutaneous coronary intervention six years prior, mildly reduced systolic function (EF 45 %), hypertension, recurrent GI bleed due to arteriovenous malformation, and hypercholesteremia. There was no known family history of GU or adrenal malignancies. Her workup included transesophageal echocardiography demonstrating severe bioprosthetic aortic stenosis and confirmed on right and left cardiac catheterization. She was scheduled for a revision open aortic valve replacement (AVR).

As part of the preoperative workup, she underwent a CT Angiogram to evaluate her aortic valve which incidentally revealed a 3cm unilateral right adrenal mass. Subsequent MRI confirmed a complex cystic/solid mass measuring 2.5x1.9 × 3.0cm with possible hemorrhagic components (Fig. 1). Consultation was obtained from the endocrine neoplasia team to assist with workup.

Fig. 1.

T2-weighted abdominal MRI with and without contrast demonstrated 3.0 x 2.5 × 1.9cm complex cystic right adrenal mass.

Biochemical evaluation included elevated plasma metanephrines and normetanephrines at 0.77nmol/L (nl. 0.00–0.49nmol/L) and 2.43nmol/L (nl. 0.00–0.89nmol/L), respectively. Dopamine was elevated at 41pg/mL (nl. 0–20pg/mL). Renin, aldosterone, LH, FSH, DHEA, cortisol, ACTH, and calcitonin levels were within normal limits (Table 1). There was discussion between pheochromocytoma versus adrenal cortical carcinoma with elevated catecholamines, however pheochromocytoma was determined to be more likely given the normal cortisol, potassium, and ACTH levels.

Table 1.

Summary table of labs for initial work up of right adrenal mass.

	Ref. Range	Lab Values pre-operatively
Metanephrine	0.00–0.49 nmol/L	0.77 (H)
Normetanephrine	0.00–0.89 nmol/L	2.43 (H)
Dopamine	0–20 pg/ml	41 (H)
Calcitonin	0.0–5.1 pg/mL	<2.0
Cortisol	Ug/dL	6.6
ACTH	7.2–63.3 pg/mL	7.4
DHEAS	9.0–246 Mcg/dl	28
Aldosterone	Ng/dL	9.1
Plasma Renin	0.25–5.82 ng/mL/h	2.5
Potassium	3.6–5.1 mmol/L	4.1

The AVR was postponed due to the pheochromocytoma finding. The patient was admitted to the hospital for medical intervention. Alpha blockade with prazosin was not tolerated due to hypotension and atrial fibrillation. metyrosine was started, and the patient was discharged on hospital day seven with a supply of metyrosine.

A multidisciplinary team including urology, anesthesia, cardiology, endocrine neoplasia, cardiac surgery, and intensive care discussed the order of laparoscopic adrenalectomy and AVR. The decision was that the valve should not be replaced with the pheochromocytoma present due to risk of cardiovascular collapse secondary to catecholamine surge. The consensus was to proceed with laparoscopic adrenalectomy first.

The patient was admitted to MICU for medical optimization before undergoing laparoscopic right adrenalectomy. Alpha blockade was reinitiated with phenoxybenzamine, but discontinued due to symptomatic hypotension. The patient was started on low dose (0.5mg) doxazosin every 12 hours with hold parameters for systolic blood pressure less than 110 mmHg, metyrosine titrated up to 250mg every six hours, and cautious intravenous hydration ahead of surgery.

The laparoscopic adrenalectomy was performed without complication. Cardiopulmonary bypass was available throughout the case, but not required since there was no hemodynamic instability. Grossly, the right adrenal gland weighed 17g and measured 4.5x3.4 × 23cm. There was a 2.4x2.2 × 1.5cm well-circumscribed mass arising from the medulla, consistent with a pheochromocytoma. Pathologic review revealed a PASS score of 12+, indicating biologically aggressive behavior, and invasion of peri-adrenal adipose tissue. Surgical margins were negative.

The patient was transferred to the ICU in stable condition and her hemodynamics were closely monitored. No significant acute postsurgical issues occurred, and the patient was discharged home on post-op day six. Catecholamines were remeasured 12 days after the surgery and were within normal limits, normetanephrine at 0.89 (nl. 0.00–0.89) and metanephrine at 0.35 (nl. 0.00–0.49) (Table 2). Following adrenalectomy, the patient denied episodes of palpitations, SOB, and diaphoresis, though dyspnea on exertion remained. Post-operative Cu-64 dotatate PET/CT scan showed no suspicious avid lesions indicating no evidence of residual or metastatic tumor.

Table 2.

Summary of metanephrine and normetanephrine levels relative to laparoscopic right adrenalectomy.

	Ref. range	2-month pre-op	1.5-month pre-op	1-month pre-op	2 weeks pre-op	2 weeks post-op	2-month post-op	6-month post-op
metanephrine	0.00–0.49 nmol/L	0.77(H)	0.60 (H)	0.62(H)	0.51(H)	0.35	0.38	0.28
normetanephrine	0.00–0.89 nmol/L	2.43 (H)	1.19 (H)	0.98 (H)	1.01 (H)	0.89	1.09 (H)	0.98 (H)

The TAVR procedure was performed without complication 33 days after the laparoscopic adrenalectomy. The patient had a 23mm transcatheter valve placed and was discharged home in stable condition the following day. On follow-up, the patient was asymptomatic with improved DOE. Abdominal CT with contrast showed no recurrent mass at seven months post adrenalectomy (Fig. 2).

Fig. 2.

7-month Post-operative Abdominal CT with contrast showing no recurrent right adrenal mass present.

3. Discussion

Evidence-based guidelines exist for management of patients with pheochromocytoma.^1,3 However, pheochromocytoma with concomitant severe aortic stenosis is far less common. This complex clinical situation warrants patient-specific consideration with a multidisciplinary team.^3,5

We report the first case of a patient with Turner syndrome with recurrent aortic valve stenosis who was incidentally found to have a pheochromocytoma. Turner syndrome is associated with congenital heart defects. Our patient had a bicuspid aortic valve with aortic stenosis and coarctation of the aorta. To date, there is no evidence for an association between Turner syndrome and pheochromocytoma. While management of pheochromocytoma and symptomatic aortic stenosis has been reported, no consensus on the order of treatment exists.

An essential aspect of treatment for pheochromocytoma patients is alpha blockade. This can be complicated by aortic stenosis due to opposing hemodynamic goals of the conditions.^2,5 Our patient did not tolerate prazosin and phenoxybenzamine, but eventually tolerated low dose doxazosin in combination with metyrosine. Coordinated multidisciplinary care with endocrine neoplasia, cardiology, cardiac surgery, anesthesia, and urology is critical to successfully manage these complex clinical scenarios.