Improvement of young-onset dilated cardiomyopathy by successful resection of pheochromocytoma

INTRODUCTION

Pheochromocytoma and paraganglioma (PPGL) is usually described as “the great masquerader” because of its wide range of clinical manifestations, starting from endocrine to metabolic, cardiac, neurological, psychiatric, and drug-induced disorders.^[1] PPGL-associated cardiomyopathies can be chronic or acute, with takotsubo cardiomyopathy being the most often reported. The pathophysiology of these two forms of PPGL-induced cardiomyopathy appears to differ. Myocardial β-adrenoceptors are overloaded by acute catecholaminergic stress, which also causes left ventricular (LV) stunning and mild histological apoptosis.^[2] Long-term catecholamine exposure in chronic cardiomyopathy leads to myocardial fibrosis, inflammation, and necrosis, which, in turn, results in dilated cardiomyopathy (DCM) with a low ejection fraction.^[3] Occasionally, hypertrophic cardiomyopathy may occur, particularly in situations linked to hypertension. With a higher hospital death rate, a higher rate of cardiogenic shock at initial presentation, and a lower rate of LV recovery following surgery, the prognosis seems to be worse in chronic cases. As a result, it is crucial to obtain an early diagnosis of PPGL.^[4] The definitive treatment for pheochromocytoma is the surgical removal of the tumor, which often significantly improves symptoms and resolves cardiac complications.^[5,6]

Managing such cases requires a delicate balance of treatments to stabilize the cardiovascular system while preparing for tumor removal. In this case report, we discuss a young boy who presented with heart failure with reduced ejection fraction due to DCM, and there was significant gradual improvement in ejection fraction after excision of pheochromocytoma.

CASE REPORT

A 16-year-old boy presented with diffuse, severe abdominal pain that recurred intermittently every 2–3 days over the past 10 days. Despite consulting multiple physicians and receiving analgesics, his symptoms persisted, leading to hospital admission. During hospitalization, he was administered a normal saline (NS) infusion, which resulted in episodes of palpitations and diaphoresis lasting 5–10 min and occurring approximately every hour. In addition, pedal edema was observed during infusion. Given these symptoms, a cardiology consultation was obtained, and a 2D echocardiogram revealed LV dysfunction with an ejection fraction of 15%. Consequently, NS infusion was discontinued, and the patient was initiated on intravenous diuretics to manage fluid overload. Over the next 4–5 days, his symptoms improved, and he was discharged.

Over the following 2 months, he remained clinically stable on diuretics, sacubitril-valsartan, aspirin, and fluid restriction, with recommendations to avoid exertion. However, 2 months later, he presented to the emergency department with complaints of cough and fever for 3 days, diffuse abdominal pain, diaphoresis, palpitations, dyspnea, and pedal edema. On examination, bilateral infrascapular crepitations were noted. A provisional diagnosis of DCM with severe LV dysfunction and congestive heart failure was established. He was managed with furosemide, milrinone, dobutamine, levosimendan, N-acetylcysteine infusion, antibiotics, ivabradine, aspirin, digoxin, carvedilol, spironolactone, and other supportive measures. The cardiothoracic and vascular surgery team advised non-contrast computed tomography (NCCT) of the chest to evaluate for pulmonary congestion, pulmonary edema, and mild bilateral pleural effusion secondary to heart failure as part of the pre-transplant workup. The scan revealed a well-defined soft tissue mass (4.9 × 4.27 cm) with central coarse calcification and hypodense necrotic areas in the left adrenal gland, raising suspicion of pheochromocytoma [Figure 1].

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Figure 1:

(a) Non-contrast chest computed tomography (axial view) of left adrenal gland: well-defined soft tissue mass (4.9 × 4.27 cm) with central coarse calcification as shown by red arrow and hypodense necrotic areas. (b) Abdominal magnetic resonance imaging (axial view) T1-weighted imaging: well-defined isointense rounded lesion (4.4 × 4.0 × 5.8 cm) in the left suprarenal region, as shown by red arrow. (c) T2-weighted imaging revealed an intermediate-intensity peripheral component and a hypointense central necrotic core as shown by red arrow.

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Further biochemical investigations confirmed the diagnosis. Plasma-free metanephrines were markedly elevated: Normetanephrines 5380 ng/L (reference <196 ng/L), metanephrines 74.8 ng/L (reference <65 ng/L), and 3-methoxytyramine 112 ng/L (reference <18 ng/L). An abdominal magnetic resonance imaging demonstrated a well-defined, rounded lesion (4.4 × 4.0 × 5.8 cm) in the left suprarenal region, showing heterogeneous peripheral enhancement with a non-enhancing central necrotic core. The lesion appeared isointense on T1-weighted imaging, whereas T2-weighted imaging revealed a heterogeneous signal intensity, with an intermediate peripheral component and a hyperintense central necrotic core [Figure 2].

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Figure 2:

Ga-68 DOTANOC PET scan: (a) Cross-sectional view - showed an SSTR-expressing soft tissue mass with central calcification arising from the left adrenal gland as shown by red arrow. (b) Coronal plane view – same finding as shown by red arrow in different view

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Surgical course and post-operative period

The patient underwent left open adrenalectomy. Intraoperatively, transient hypotension (72/48 mmHg) occurred following adrenal vein clamping and was managed with intravenous fluids and inotropic support.

In the immediate post-operative period (post-operative day 0), blood pressure ranged between 80 and 90/50 and 60 mmHg with a heart rate of around 100 beats/min. Over the next several days, blood pressure progressively stabilized to 118/64 mmHg with heart rate decreasing to 90 beats/min by post-operative day 9 [Table 1b]. Inotropic support was gradually tapered and discontinued by post-operative day 9, with sustained hemodynamic stability.

Table 1b: Vitals - blood pressure and pulse rate postoperatively.

Parameters	POD 0	POD 1	POD 2	POD 3	POD 4	POD 5	POD 6	POD 8	POD 9
Blood pressure (mmHg)	80–90/50–60	100–110/58–60	114/66	101/59	115/69	92/55	98/56	112/60	118/64
Heart rate (beats/min)	100	86	93	86	98	98	102	96	90

POD: Post-operative day

Histopathological examination confirmed pheochromocytoma with a classical Zellballen pattern. The Pheochrocytoma of the Adrenal Gland Scaled Score (PASS) score was 4/20. There was no lymph node involvement, no metastasis, and margins were negative (R0 resection). Immunohistochemistry was positive for Ki-67 and chromogranin [Figure 3]. Clinical exome sequencing was performed, which revealed a heterozygous autosomal-dominant SCN5A missense variant; however, this is presently classified as a variant of uncertain significance, and there is no clinical correlation of our case with diseases described in the literature.

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Figure 3:

(a) Zellbalenpattern -Tumour consists of nests of spindle or polyglonal cells (as shown by red arrow). (b) Nests are separated by delicate fibrovascular stroma as shown by red arrow. (c) Ki- 67 Staining as shown by red arrow. (d)Chromogranin staining as shown by red arrow.

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DISCUSSION

PPGL-induced cardiomyopathy encompasses a spectrum from transient takotsubo-type cardiomyopathy (TTC) to chronic dilated forms (congestive cardiomyopathy [CC]/dilated cardiomyopathy [DCM]), both driven by catecholamine excess, with TTC demonstrating superior LV recovery following tumor resection. The 2016 Batisse–Lignier systematic review analyzed 152 such cases, stratifying them into TTC (acute, reversible apical ballooning; n = 46) and CC (chronic, dilated; n = 106); pre-operative LV recovery was markedly higher in TTC (69% [25/36] vs. 41% [31/76]; P = 0.005), rising postoperatively to 98% in TTC (42/43) versus 73% in CC (55/75; P = 0.001), with multivariate analysis confirming TTC as the independent predictor of recovery (P = 0.03) despite equivalent baseline severe LV dysfunction. In-hospital mortality trended higher in CC (10% vs. 2%; P = 0.10).^[7]

Conversely, Sardesai et al. described six pheochromocytoma patients with fulminant catecholamine cardiomyopathy presenting as heart failure, where five succumbed to pulmonary edema within 24 h; autopsies (n = 4) showed focal myocardial necrosis with inflammatory infiltrates and contraction bands —pathognomonic of acute catecholamine toxicity—underscoring the peril of delayed diagnosis.^[8] Mechanistically, both entities arise from β1-mediated calcium overload, microvascular spasm, and oxidative stress, though CC involves chronic β-adrenergic receptor kinase upregulation and eccentric remodeling; TTC mimics acute coronary syndrome (ACS) with ST-elevation and troponin rise but spares coronaries, necessitating early α/β-blockade pre-resection, while echo/cardiac magnetic resonance differentiates regional (TTC) from global hypokinesis (CC).^[2]

CONCLUSION

Diagnosing and managing pheochromocytoma-induced cardiomyopathy poses significant clinical challenges due to its ACS mimicry, catecholamine crisis risks, and variable phenotypes. A personalized and dynamic approach was essential to carefully balance inotropic support versus beta-blockade, diuresis versus volume loading (NS and salt intake), and alpha-blockade in the context of cardiogenic shock. The successful surgical outcome and post-operative stability of this complex patient were achieved through a highly coordinated multidisciplinary strategy involving endocrinology, cardiology, anesthesia, and critical care teams. Therefore, pheochromocytoma, a rare condition, should be considered a differential diagnosis in young patients presenting with unexplained hypertension, chest pain, and cardiac dysfunction.