Acute heart failure with incidentally found cystic adrenal mass

Background

We present the case of a previously healthy female who presented with acute decompensated heart failure. Acute heart failure is a rare diagnosis in healthy subjects, and nonvascular causes need to be evaluated. During imaging, a large cystic adrenal mass was discovered, which was suspicious for an adrenal hemorrhage. This, along with a significant elevation of plasma metanephrines, was consistent with acute hemorrhage of pheochromocytoma resulting in a pheochromocytoma crisis. Pheochromocytoma crisis typically occurs with trauma or the use of drugs, but can rarely be triggered by a spontaneous bleed, as was the case in our patient. The catecholamine surge during a pheochromocytoma crisis results in myocardial stunning and stress cardiomyopathy, which is often reversible. Management of these patients can be challenging, with diagnostic and treatment hurdles. Acute medical management is recommended; emergent surgical management of the hemorrhagic pheochromocytoma has higher morbidity and mortality.

Case presentation

Our patient is a 52-year-old female who had been evaluated by a cardiologist one year prior for intermittent palpitations, with weakness and mild nausea developing during a similar but less intense episode. A 14-day cardiac event monitoring 8 months prior to current event had shown intermittent supraventricular tachycardia (SVT) with no symptomatic episodes. An echocardiogram had shown a normal left ventricular ejection fraction (LVEF) of 60% and no valvular dysfunction.

She developed acute onset of chest pain, light-headedness, vomiting, and numbness while she was at rest at home. She was brought to the ED of another hospital, where vital signs showed hypotension (84 mm/60 mm Hg), tachycardia (102 bpm), and hypoxia (91%). The exam showed signs of acute congestive heart failure (ACHF) with bilateral crackles. Initial labs were notable for low hemoglobin of 8.7 mg/dL (12–15), and thrombocytopenia 95 000/mm³ (150–400). Troponin I was elevated at 2.78 ng/mL, increasing to 4.1 ng/mL (<0.04 ng/mL). N-terminal pro b-type natriuretic peptide (NT-proBNP) was elevated at 643.0 pg/mL (<125). Lactic acid was elevated at 5 mmol/L (0–2 mmol/L). Thyroid-stimulating hormone was normal at 1.24 mIU/L. EKG showed sinus rhythm with a heart rate of 95 bpm incomplete right bundle branch block, left axis deviation, and ST-segment elevations in the V1, V2, and aVR leads. Echocardiogram showed overall depressed left ventricular systolic function with ventricular ejection fraction visually estimated at 25–30%; normal right ventricle structure and function. Severe mitral regurgitation with posteriorly directed jet and mild tricuspid regurgitation present. CT angiogram ruled out pulmonary embolism but showed pulmonary congestion.

Due to concern of an ischemic event, cardiac catheterization was performed, which showed normal coronary arteries, but elevated LV end-diastolic pressures (27 mm Hg) and elevated pulmonary capillary wedge pressure (29 mm Hg), consistent with ACHF.

Because of acute respiratory distress, she was intubated soon after arrival at the ED. She was initiated on dobutamine, furosemide, and heparin drips. Intra-aortic balloon pump (IABP) was used for inotropic support. The patient’s clinical status improved over the next 3 days, and she was extubated with cessation of IABP and vasopressors.

A repeat echocardiogram performed 4 days after admission showed resolution of the previously decreased LVEF (now 65%) and of mitral regurgitation.

CT abdomen/pelvis showed a large posterior left upper quadrant cystic mass measuring 8.4 × 7.1 × 9.2 cm, inferiorly displacing the left kidney and anteriorly displacing the stomach, with peripheral areas of increased density (noncontrast CT density of 32 Hounsfield units (HU)), potentially representing a left adrenal mass or a pancreatic tail mass (Fig. 1A). No lymphadenopathy was noted on chest/abdominal imaging. She underwent a fine needle aspiration (FNA) biopsy of the left intra-abdominal mass, which showed clotted blood and no malignant cells.

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A: CT Adrenal with contrast at time of hospitalization showing 8.4 × 7.1 × 9.2 cm cystic adrenal mass with peripheral hyper-enhancing rim, displacing the left kidney downwards. B: CT Adrenal with contrast done 5 months after hospitalization showing decreased size of complex partially cystic left adrenal mass with predominant centrally complex hypodense/complex cystic component without enhancement thickened enhancing peripheral rim, measuring 3.7 × 3.6 × 4.2 cm.

Citation: Endocrinology, Diabetes & Metabolism Case Reports 2023, 4; 10.1530/EDM-23-0051

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Plasma fractionated metanephrine was 2555 pg/mL (0–96) and normetanephrine 1559 pg/mL (0–175), respectively, drawn 2 days after admission. Spot urine metanephrine-to-creatinine ratio was 10 062 µg/g (0–300 µg/g) and normetanephrine to creatinine ratio was 3090 µg/g (0–400 µg/g). Testing for infectious (Coxsackievirus, influenza virus, severe acute respiratory syndrome coronavirus 2 antigen, parvovirus), and rheumatologic/autoimmune pathologies (ANA, SSA, SSB, dsDNA) was negative. Complement levels were normal. Serum ferritin was 632 ng/mL on admission and improved to 286 ng/mL at discharge (11–264 ng/mL).

Investigation

Repeat testing showed normal plasma metanephrine (30.2 pg/mL 2 weeks and 20.8 pg/mL 3 months after admission (0–88 pg/mL)), and plasma normetanephrine (136 pg/mL 2 weeks and 134 pg/mL 3 months after admission (0–244 pg/mL)). The spot urinary metanephrine to creatinine ratio was 0.5 µg/mg (0–1 µg/mg).

CT of the abdomen 8 months post hospitalization showed a complex partially cystic/hypodense left adrenal mass (nonenhanced average – 25 HU), significantly decreased in size (3.7 × 3.6 × 4.2 cm vs 8.4 × 7.1 × 9.2 cm at diagnosis) with thickened enhancing peripheral rim measuring 1 cm in size (postcontrast 120 HU) (Fig. 1B).

Treatment

She was discharged on metroprolol succinate 50 mg once a day, and 1 week after discharge she was switched to labetalol by her primary care provider. She was soon (within 2 weeks from discharge) evaluated by the endocrine team in our hospital. A possible underlying pheochromocytoma was suspected, but could not be confirmed biochemically after hospital discharge, as plasma metanephrines were normal in two separate draws. She was maintained on a small dose (100 mg twice a day) of labetalol for 9 months, then switched to alpha-blockade with dozazosin 1 mg/day for 1 month prior to a robot-assisted left laparoscopic adrenalectomy was performed 10 months after her initial admission. An 11.5 × 6.5 × 3.7 cm red-brown, smooth, specimen weighing 44 g with attached yellow-tan, lobulated adipose tissue was resected, without any intraoperative complications. She was discharged on no medication.

Outcome and follow-up

The patient did well postoperatively and was discharged without any blood pressure medications. She has been asymptomatic since surgery and regular blood pressure checks have been in the normal range. The gross section of the surgical specimen showed a 4.2 × 3.7 × 2.5 cm tan-brown, well-circumscribed, centrally hemorrhagic, and cavitated mass, containing red-brown, friable material, that was located 0.1 cm from the nearest capsular margin. The uninvolved portion of the adrenal gland noted a normal cortex and no additional lesions.

Pathology showed pheochromocytoma, with extensive fibrosis, hemosiderin deposition, and fibrin, consistent with a prior hemorrhage. Immunostaining was positive for GATA-3 and synaptophysin and negative for AE 1/3 (Fig. 2). The PASS score was 2.

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A: H&E, 2× objective. Benign adrenal cortical tissue (bottom) and dense fibrous tissue (top) resulting from prior hemorrhage sandwiching the pheochromocytoma. B: H&E, 10× objective. Fibrosis (bottom) and hemosiderin-laden macrophages (top) intermingled with red blood cells, rare multinucleated giant cells, and histiocytes, all evident of a prior hemorrhage. C: Pheochromocytomas may demonstrate the ‘Zellballen’ pattern outlined by sustentacular cells (not visualized). D, E: GATA3 (left), Synaptophysin (right) immunostains, 10× objective. Pheochromocytomas are positive for GATA3 (nuclear) and synaptophysin (cytoplasmic).

Citation: Endocrinology, Diabetes & Metabolism Case Reports 2023, 4; 10.1530/EDM-23-0051

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Discussion

Heart failure is an uncommon diagnosis in an otherwise healthy female and warrants evaluation of secondary causes. Noncardiovascular causes of heart failure include viral infections (Coxsackievirus, parvovirus, coronavirus, human herpes virus 6, human immunodeficiency virus), peripartum cardiomyopathy, amyloidosis, hereditary hemochromatosis, sarcoidosis, rheumatologic conditions (systemic lupus erythematosus, rheumatoid arthritis), familial (genetic) syndromes, illicit drugs (cocaine, alcohol), vitamin/mineral deficiencies (thiamine, selenium), and drug toxicity (doxorubicin, trastuzumab). The workup of our patient did not show any evidence of these etiologies. While cardiac magnetic resonance imaging (MRI) is an excellent modality to diagnose the etiology of systolic/diastolic dysfunction, due to the rapid recovery of cardiac function (typically not seen in viral myocarditis), adrenal tumor on imaging, and significantly elevated metanephrine levels, we deemed pheochromocytoma as the likely etiology, and this test was not performed. Nevertheless, without MRI, acute myocarditis cannot be excluded.

Differential diagnosis of a cystic adrenal mass includes adrenal endothelial cyst, hemorrhagic adrenal adenoma (pseudocyst), cystic pheochromocytoma, adrenocortical carcinoma, or rarely parasitic infections. Pheochromocytomas are typically solid homogenous masses, but in rare cases, can present as masses with cystic changes, necrosis, and internal calcifications (1). Being hypervascular, they are at an increased risk of bleeding. Cystic pheochromocytomas may thus develop through hemorrhage and necrosis of the solid component.

Pheochromocytoma can be undiagnosed in 20–40% of cases; however, the incidence is rising due to the widespread use of cross-sectional imaging finding incidental adrenal masses (2). Our patient had symptoms of palpitations a year before the acute heart failure, which was possibly a manifestation of the underlying hyperadrenergic state.

Pheochromocytoma is a rare cause of acute decompensated heart failure, resulting in stress cardiomyopathy (SCM) as in our patient, who had a normal cardiologic evaluation just 10 months ago (3). SCM likely results from an acute surge of catecholamines, which causes microvascular spasms, generation of free radicals, increased beta-adrenergic receptor internalization, increased sarcolemmal permeability (leading to abnormal intracellular calcium accumulation), and direct myocardial injury, resulting in myocardial stunning and transient left ventricular dysfunction (4, 5). Other chronic mechanisms of cardiomyopathy in pheochromocytoma include chronic hypertension catecholamine-mediated myocyte fibrosis and tachycardia-induced cardiomyopathy.

The typical culprits of the catecholamine surge, resulting in crises include trauma, surgical manipulation, and medications (antidepressants (TCAs, SNRI, MAOIs), D-2 receptor blockers, nonselective beta-blockers, sympathomimetics, glucocorticoids), none of which was present in our case, who therefore likely had a spontaneous bleed of pheochromocytoma.

The high levels of metanephrine and normetanephrine during hospitalization can be difficult to interpret for diagnosis of pheochromocytoma, with physiologic elevations seen in critically ill patients or due to medication-related changes (use of vasopressors). No cut-off values of metanephrines have been established to distinguish between the two clinical situations. Kline et al. showed a significant overlap of urinary metanephrine testing in critically ill patients and patients with diagnosed pheochromocytoma (particularly urinary normetanephrine), with increased specificity being achieved when levels were above 5× the upper limit, although still not achieving strong predictive values (6). Thus, early imaging should be pursued in critically ill patients to establish or rule out the presence of a pheochromocytoma, which will help in changing the pretest probability and guide appropriate treatment (7). Elevation of fractionated metanephrine is more specific for pheochromocytoma (8).

In our patient plasma metanephrines had already normalized 2 weeks after the acute event, possibly due to the extent of hemorrhage and necrosis of most of the tumor. Serial imaging showed a significant decrease in tumor size over 8 months, with only a rim of enhancing tissue. Pathology showed only a 1 cm rim of intact tumoral tissue, with most of the tumor mass being necrosed. Indeed, smaller pheochromocytomas have lower and often normal metanephrine levels (9).

FNA biopsy of the adrenal lesion, performed in our case, was not the appropriate diagnostic step. FNA of adrenal mass is usually performed to assess for suspicion of metastatic disease when the result impacts the management strategy. Complications include rupture of the contained hemorrhage, precipitation of pheochromocytoma crisis, and tracking of malignant cells in case of underlying adrenocortical carcinoma. Therefore, FNA biopsy of the adrenal mass should not be performed until pheochromocytoma is ruled out.

If a pheochromocytoma is diagnosed in the acute SCM phase, surgery is not typically recommended due to high mortality (10). The patient should be adequately alpha blocked before surgery for better outcomes. Recovery of cardiac function is dependent on the time frame of catecholamine exposure to the myocytes, with higher chances of recovery in SCM and lower in chronic exposure, which leads to myocyte fibrosis.

This case shows that acute SCM can occur after spontaneous hemorrhage in a previously undiagnosed pheochromocytoma, and that plasma metanephrines may be persistently normal in a pheochromocytoma after hemorrhage.

Declaration of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding

This work did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.

Patient consent

Written informed consent for publication of clinical details and/or clinical images was obtained from the patient.

Patient’s perspective

Every story has a silver lining. I hope mine can help someone who might face something similar. A year prior to my ‘incident’ I experienced an episode of dizziness, shaking, and rapid heart palpitations which took me to a cardiologist for the first time. My ekg was normal and I wore a heart monitor for a few weeks. Nothing out of the ordinary was discovered. One year later, almost to the date, I felt the same symptoms but all more severe with nausea, vomiting and the knowledge that something was seriously wrong. When I arrived in the ED it took some time to determine that I was suffering heart failure. Incidentally, a 9 centimeter abdominal mass was discovered. I had no stomach pain at all. I was rushed to the catheterization lab where a balloon pump was inserted and I was put on a ventilator. Both were necessary and life saving but mostly terrifying and shocking. It is still so vivid. All the medications and the fear of not waking made it nearly impossible for me to sleep. I was scared to close my eyes at all. Several days later I was told that the biopsy on the mass in my stomach was found to be blood, that my heart quickly corrected and that I was ready to come off the ventilator. It seemed I had somewhat of a miraculous recovery. One week later I was released from the hospital with a stress-induced cardiomyopathy diagnosis. With no family history and a healthy lifestyle I just couldn’t wrap my brain around it. A week later my discharge doctor called to let me know that after further analysis of my bloodwork and testing they suspect that my heart failure was caused by a pheochromocytoma that ruptured. This was something I had never heard of and knew nothing about except that it was extremely rare. 10 months and 3 CTs later it was clear that the mass was shrinking but still needed to be removed. I had a successful adrenalectomy which was complex and required very precise surgical skills. Pathology was able to confirm that it was, in fact, a pheochromocytoma. Aside from a few small abdominal scars I am well on the mend. I participate in a monthly post intensive care support group and thank God every day for my supportive family and friends and my most incredible team of nurses and doctors.

Author contribution statement

SZB evaluated the published data, drafted, and edited the manuscript. AH was involved in editing the manuscript. YW was involved in preparing, reporting, and describing the pathology images. MH was involved in the patient care and edited the manuscript. RS was involved in patient care and edited the manuscript.