Pheochromocytoma presenting with vomiting and heart failure: A case report

Abstract

BACKGROUND

Pheochromocytoma, a rare catecholamine-secreting tumor, typically presents with the classic triad of headache, palpitations, and diaphoresis, often accompanied by cardiovascular manifestations. While vomiting occurs in approximately 34.5% of cases, it is rarely the predominant and persistent presenting symptom. Pheochromocytoma-induced cardiomyopathy leading to heart failure is a recognized but uncommon complication. Due to its heterogeneous presentations, misdiagnosis and diagnostic delay are frequent.

CASE SUMMARY

A 53-year-old female presented predominantly with persistent and refractory vomiting as her chief complaint, accompanied by signs of acute heart failure [left ventricular ejection fraction (LVEF) 30%]. Initial evaluation at a primary hospital, including coronary angiography (revealing only mild stenosis), led to a misdiagnosis of coronary artery disease. Despite standard anti-thrombotic, anti-heart failure, and anti-emetic therapy, her vomiting persisted and heart failure did not resolve. Subsequent hospitalization revealed dramatic paroxysmal hypertension (202/129 mmHg to 97/51 mmHg) and fever. Significantly elevated plasma metanephrines and normetanephrine, combined with abdominal computed tomography and magnetic resonance imaging, confirmed a right adrenal pheochromocytoma. This diagnosis was significantly delayed due to the atypical prominence of gastrointestinal symptoms masking the underlying endocrine crisis.

CONCLUSION

This case highlights a highly atypical presentation of pheochromocytoma dominated by refractory vomiting and complicated by acute catecholamine-induced cardiomyopathy. It emphatically underscores that pheochromocytoma must be considered in the differential diagnosis for patients presenting with unexplained, treatment-resistant vomiting, particularly when co-existing with acute heart failure. The presence of labile hypertension, even if not initially evident, provides a crucial diagnostic clue. Prompt biochemical screening (catecholamine metabolites) and adrenal imaging are essential to prevent diagnostic delay and enable timely, life-saving surgical intervention.

Key Words: Pheochromocytoma; Vomit; Heart failure; Catecholamine; Cardiomyopathy; Case report

Core Tip: This case highlights an exceptionally atypical presentation of pheochromocytoma dominated by refractory vomiting and complicated by acute catecholamine-induced cardiomyopathy with heart failure (left ventricular ejection fraction 30%). Initial misdiagnosis as coronary artery disease occurred due to mild stenosis on angiography. The critical diagnostic clue emerged with dramatic paroxysmal hypertension (fluctuating from 202/129 mmHg to 97/51 mmHg). This report underscores that pheochromocytoma must be considered in patients with unexplained treatment-resistant vomiting coexisting with acute heart failure, particularly when labile hypertension appears. Timely biochemical screening (catecholamine metabolites) and adrenal imaging are essential to prevent life-threatening delays.

INTRODUCTION

Pheochromocytoma is a rare endocrine tumor originating in the chromaffin tissue of the neuroectoderm. Its secreted catecholamine can cause persistent or paroxysmal hypertension, multiple organ dysfunctions and metabolic disorders. The most common symptoms include a triad of headache, palpitations and diaphoresis.

While nausea and vomiting symptoms occur in 34.5% of cases[1], these are rarely the dominant and most persistent presenting symptoms, as observed in this patient. This atypical presentation can lead to diagnostic challenges and delays, and is associated with higher mortality[1]. Furthermore, the concomitant presentation of acute heart failure at admission significantly deviates from the classic triad, which may be associated with elevated catecholamine levels[2]. This unusual combination of symptoms, where refractory vomiting dominates the clinical presentation alongside acute heart failure, presents a significant diagnostic challenge and often leads to delayed recognition. Given the high misdiagnosis rate of pheochromocytoma-related hypertension and digestive symptoms, it is crucial to combine imaging and blood pressure monitoring to better analyze clinical symptoms and guide treatment.

CASE PRESENTATION

Chief complaints

Recurrent chest tightness accompanied by nausea and vomiting for 9 days.

History of present illness

A 53-year-old female presented to the emergency department with recurrent chest tightness, nausea, and vomiting lasting 9 days, representing her second hospitalization for these symptoms. Ten days previously, emotional distress due to family changes precipitated sudden nausea, vomiting, chest tightness, and diarrhea, prompting evaluation at a primary hospital. Initial testing revealed elevated B-type natriuretic peptide (BNP) and troponin, electrocardiography (ECG) showed sinus rhythm with ST-T changes, and coronary angiography identified 30% stenosis with mild thrombus in the mid-left anterior descending artery. She was discharged on anti-thrombotic and gastric-protective therapy but experienced worsening vomiting and chest discomfort, leading to transfer to our institution.

Upon admission, echocardiography demonstrated uncoordinated left ventricular wall motion, severely reduced systolic function (ejection fraction 30%), moderate tricuspid regurgitation, and hypovolemia; ECG revealed sinus tachycardia (137 bpm), and biomarkers confirmed significant cardiac stress (troponin 192.2 pg/mL, myoglobin 320.0 ng/mL, BNP 9737 pg/mL). Diagnosed with acute heart failure, she received nitroglycerin and natriuretic peptide and was admitted to cardiology. During hospitalization, she developed persistent dyspnea and refractory vomiting despite standard heart failure therapy (diuretics, natriuretic peptide), hypoglycemic agents for type 2 diabetes, and anti-infectives. Gastrointestinal and neurological investigations including normal serum amylase and unremarkable head computed tomography (CT) failed to explain her symptoms. Concurrently, she manifested dramatic paroxysmal hypertension and intermittent fever.

This combination of refractory cardiac and gastrointestinal symptoms that were more severe than expected given the mild coronary disease, along with extreme hemodynamic lability and unexplained fever, raised suspicion for catecholamine excess. Biochemical testing confirmed profound elevations in catecholamine. Abdominal CT revealed a right adrenal mass, subsequently confirmed as pheochromocytoma by adrenal magnetic resonance imaging (MRI), establishing the definitive etiology of her presentation.

History of past illness

The patient's history of past illness also indicated that she was diagnosed with diabetes mellitus 1 year ago and has been controlling her blood sugar through oral metformin, 2 tablets twice daily.

Personal and family history

The patient denies any family history of genetic diseases or similar conditions.

Physical examination

On admission, physical examination revealed a temperature of 37°C, pulse rate of 89 bpm, respiratory rate of 14 breaths per minute, and blood pressure of 122/74 mmHg. Cardiac examination showed a normally positioned heart with the apex beat palpable 0.5 cm medial to the left midclavicular line in the fifth intercostal space; heart sounds were regular at 89 bpm with normal S1 and S2 intensity, absent murmurs or extra sounds. Abdominal assessment demonstrated a flat, non-tender abdomen without palpable masses or hepatosplenomegaly. However, during hospitalization, she developed dramatic hemodynamic instability characterized by paroxysmal hypertension with extreme diurnal fluctuations (e.g., 202/129 mmHg to 97/51 mmHg) and nocturnal excursions (201/115 mmHg to 121/56 mmHg), accompanied by intermittent fever spiking to 39.0°C.

Laboratory examinations

Initial testing at the primary hospital revealed elevated serum BNP and troponin. Upon admission to our hospital, plasma biomarkers confirmed significant cardiac stress, including troponin (192.2 pg/mL), myoglobin (320.0 ng/mL), and markedly elevated BNP (9737 pg/mL). Blood amylase was subsequently measured to investigate persistent nausea and vomiting, with results within normal limits. During the diagnostic workup for catecholamine excess, biochemical testing demonstrated profound elevations: Noradrenaline (7.99 nmol/L), metanephrine (> 10.14 nmol/L), normetanephrine (8.37 nmol/L), epinephrine (> 10.917 nmol/L), homovanillic acid (579.89 nmol/L), and vanillylmandelic acid (> 605.532 nmol/L), with dopamine at 0.19 nmol/L, confirming catecholamine hypersecretion.

Imaging examinations

At the primary hospital, an initial ECG showed sinus rhythm with ST-T changes. Coronary angiography identified mild disease with 30% stenosis and a thrombus shadow in the near-middle left anterior descending artery; no significant stenosis was noted in other coronary vessels. Upon transfer to our institution, emergency department ECG revealed sinus tachycardia (137 bpm; Figure 1). Echocardiography demonstrated uncoordinated left ventricular wall motion, severely reduced systolic function (ejection fraction 30%), moderate tricuspid regurgitation, and hypovolemia. A head CT ruled out intracranial causes of vomiting, showing no abnormalities. Subsequent abdominal CT revealed a mixed-density mass in the right adrenal region (Figure 2), while chest CT incidentally noted two pulmonary nodules and tracheal diverticula. Adrenal MRI confirmed a right adrenal pheochromocytoma (Figure 3).

Figure 1  Electrocardiograph showed sinus tachycardia, T wave changing, and prolonged QT interval.

Figure 2  Abdominal enhanced computed tomography scan showing a mixed density 75 mm × 65 mm mass, in the right adrenal gland.

Figure 3 Abdominal magnetic resonance imaging revealing a pheochromocytoma located in the right adrenal gland. A: Axial; B and C: Coronal.

MULTIDISCIPLINARY EXPERT CONSULTATION

We did not consult a multidisciplinary team.

FINAL DIAGNOSIS

The patient was finally diagnosed with: (1) Class III heart function [New York Heart Association (NYHA) classification]; (2) Pheochromocytoma-induced hypertension; (3) Coronary atherosclerosis; and (4) Type 2 diabetes mellitus.

TREATMENT

The patient decided to return home for surgical treatment at a local hospital.

OUTCOME AND FOLLOW-UP

A significant limitation of this case report is the absence of follow-up data. After diagnosis was confirmed, the patient opted for surgical management at their hometown hospital and was subsequently lost to our follow-up. This precludes assessment of critical outcomes such as the resolution of cardiomyopathy, normalization of hemodynamics, cessation of vomiting, confirmation of complete tumor resection, and long-term biochemical remission or genetic testing results. The absence of this information limits our understanding of the full clinical trajectory and recovery potential following pheochromocytoma removal in this complex presentation.

DISCUSSION

This case exemplifies the significant diagnostic challenges of pheochromocytoma, particularly when presenting with atypical features dominating the clinical picture. While the tumor's adrenal location and final diagnosis via imaging and biochemistry were typical, the patient's initial and persistent presentation centered on refractory vomiting and profound acute heart failure [left ventricular ejection fraction (LVEF) 30%]. This was quite different from the classic signs of headache, palpitations and diaphoresis. This divergence led to considerable diagnostic delay and initial misdiagnosis.

Understandably, the focus at the primary hospital was on the prominent gastrointestinal symptoms and acute cardiac dysfunction. The finding of mild coronary stenosis on angiography further anchored the diagnosis towards ischemic heart disease. However, the patient's persistent vomiting and inadequate improvement in cardiac function despite appropriate conventional therapy for heart failure, potential ischemia, and nausea created a critical diagnostic impasse. Common gastrointestinal and neurological causes for vomiting were reasonably excluded, yet the etiology remained elusive. The pivotal diagnostic turning point was the emergence of dramatic, paroxysmal hypertension with extreme fluctuations (202/129 mmHg to 97/51 mmHg) and unexplained fever. This profound hemodynamic lability, highly unusual in common gastrointestinal disorders or uncomplicated heart failure, strongly suggested unregulated catecholamine surges, prompting the crucial biochemical testing that confirmed the diagnosis.

While vomiting occurs in approximately one-third of pheochromocytoma cases[1], it is rarely the dominant and most persistent presenting symptom, as in this patient. The process of vomiting is controlled by a balance between the gastrointestinal enteric nervous system and the central nervous system. The pathogenesis of vomiting in pheochromocytoma is likely multifactorial, involving direct effects of catecholamines (particularly dopamine) on receptors in the brainstem and gastrointestinal tract, disrupting the emetic control pathways[3,4]. More critically, the presence of vomiting has been associated with significantly higher mortality, often linked to crisis presentation[1].

Similarly, acute heart failure in this context is a serious complication directly attributable to catecholamine excess. High levels of catecholamines cause coronary vasospasm, myocardial stunning, increased oxygen demand, and direct toxic effects on cardiomyocytes, leading to catecholamine-induced cardiomyopathy and acute heart failure[5-7]. It has been found that a fairly complex network of Ca²⁺ overload, oxidative stress, mitochondrial dysfunction, apoptosis, interstitial fibrosis, hypertrophy, and inflammation underlies catecholamine-induced cardiotoxicity[5]. The co-occurrence of refractory vomiting and acute heart failure, especially when accompanied by hemodynamic instability, should strongly raise the possibility of an underlying catecholamine-secreting tumor like pheochromocytoma.

Pheochromocytoma is most common in people aged 20-50 years, and there is no significant difference in incidence between men and women. Among the clinical symptoms, the main manifestations of the cardiovascular system include paroxysmal hypertension, hypotension and shock, and catecholamine cardiomyopathy. Among them, hypertension is divided into two types: Paroxysmal and persistent, and persistent people can also have paroxysmal intensification[8]. Large retrospective case studies have detailed the prevalence of hypertension between 51% and 90% in pheochromocytoma patients[9,10]. Therefore, paroxysmal hypertension in this case has a good diagnostic role, which is also one of the breakthrough points in the diagnosis of this case. Additionally, pheochromocytoma can cause metabolic disturbances (e.g., glucose, lipid, electrolyte)[11,12] and other systemic effects like gastrointestinal issues, renal failure, abdominal mass, reduced blood volume, and leukocytosis[13-15].

Many patients have paroxysmal symptoms prior to diagnosis, suggesting excessive catecholamine release. Catecholamine examination can be performed in patients, and imaging examinations such as CT and MRI are essential for localization in pheochromocytoma. Due to episodic catecholamine release, false negatives can occur, so timing and potentially repeat testing are important. On CT, pheochromocytoma may have attenuation values of less than 10 Hounsfield units and may display more than 60% washout of contrast agents on delayed scanning[16]. MRI typically shows T2-weighted hyperintensity resembling cerebrospinal fluid[16].

While previous case reports have documented pheochromocytoma presenting with vomiting or cardiomyopathy individually, the constellation of refractory vomiting as the dominant symptom, severe acute heart failure, and extreme hemodynamic lability in this case is exceptionally rare. For instance, Amina Abid reported a normotensive pheochromocytoma case initially presenting with abdominal pain and vomiting, but without cardiac involvement, which was later linked to neck swelling and medullary thyroid cancer[17]. Conversely, Pirbhat Shams described a 42-year-old woman who presented with heart failure and was found to have pheochromocytoma-induced Takotsubo-like cardiomyopathy[18]. Chen et al[19] reported a 21-year-old male with no hypertensive history who presented with congestive heart failure due to pheochromocytoma-related cardiomyopathy, and hypertension was detected at follow-up. Neither of these cases featured prominent gastrointestinal symptoms. Our case uniquely combines gastrointestinal and cardiac features, further complicated by delayed diagnosis due to initial misattribution to coronary disease. This highlights the need for heightened vigilance when gastrointestinal and cardiac symptoms coexist inexplicably.

In short, although the symptoms of patients are different, related symptoms have a certain suggestive role. Survey data shows that 21.2% of patients have the classic triad of headache, sweating and palpitations, 33.9% have one or two classic symptoms, and 12.7% have other paroxysmal symptoms[20]. Significant blood pressure fluctuations strongly suggest catecholamine excess, and 24 hour ambulatory blood pressure monitoring can assist in diagnosis. The core diagnostic approach combines recognition of suggestive symptoms with biochemical testing and imaging. The distinctiveness of our case lies in the patient presenting predominantly with refractory vomiting and acute heart failure, ultimately traced to pheochromocytoma. Therefore, pheochromocytoma warrants consideration in patients presenting concurrently with heart failure and unexplained vomiting. Advances in imaging (CT, MRI, abdominal ultrasound) continue to improve detection rates. Given its rarity and diverse symptom constellation, clinicians must remain vigilant for characteristic signs to facilitate timely diagnosis.

CONCLUSION

Pheochromocytoma is a rare catecholamine-secreting tumor capable of inducing multi-system dysfunction through catecholamine excess. This case exemplifies a highly atypical presentation dominated by refractory vomiting and acute heart failure, compounded by significant diagnostic delay. Accurate diagnosis relies on identifying key characteristic clues, especially labile hypertension, amidst non-specific symptoms, and is supported by targeted biochemical testing and adrenal imaging. Crucially, it underscores that pheochromocytoma must be considered in patients with unexplained vomiting and concurrent heart failure, especially when hypertension fluctuates dramatically. Timely diagnosis is imperative, as surgical resection not only offers cure but may reverse catecholamine-induced cardiomyopathy and prevent life-threatening crises.

ACKNOWLEDGEMENTS

The authors would like to express their gratitude to the patient for granting permission to publish this case report.