A diagnostic puzzle: when pheochromocytoma meets tuberculosis!

Abstract

The association between tuberculosis and pheochromocytoma is extremely rare, although their clinical manifestations may overlap. This report presents a case of pheochromocytoma associated with pulmonary tuberculosis. Such an uncommon coexistence highlights the importance of considering infectious etiologies when evaluating adrenal pathology, particularly in regions where tuberculosis is endemic, underlines the critical role of radiological imaging in identifying dual pathology and ensuring appropriate management.

Introduction

Pheochromocytoma is a rare neuroendocrine tumor found in approximately 0.1%-0.6% of patients with hypertension [1]. Its clinical presentation is highly variable and may include headaches, palpitations, and diaphoresis, which are the most commonly reported symptoms. Respiratory manifestations, particularly hemoptysis, are rare in patients with pheochromocytoma. When present, the underlying mechanisms remain poorly understood; several hypotheses have been proposed, including catecholamine-induced vascular injury and immune-mediated processes. Reports of pheochromocytoma presenting as diffuse alveolar hemorrhage are exceedingly uncommon, with only a limited number of cases described in the literature. Early recognition of this potentially life-threatening manifestation is therefore critical [1].

Tuberculosis remains one of the leading causes of death from infectious diseases worldwide, disproportionately affecting low- and middle-income countries where socioeconomic and healthcare challenges persist. Hemoptysis is a frequent and classic manifestation of pulmonary tuberculosis, with severity ranging from mild blood-streaked sputum to massive, life-threatening hemorrhage [2]. In tuberculosis-endemic regions, this common presentation may obscure or delay the diagnosis of other rare underlying conditions.

This case reports a pheochromocytoma with triple organ involvement—pulmonary, cardiac, and renal—coexisting with pulmonary tuberculosis. It illustrates the diagnostic challenges posed by overlapping imaging findings and emphasizes the importance of comprehensive imaging evaluation.

Case presentation

A 32-year-old male patient with a history of smoking, ongoing cannabis use, and arterial hypertension diagnosed 2 years prior without etiological assessment presented for evaluation. He had never been treated for tuberculosis and reported no recent exposure. One month before admission, he developed a productive cough with yellowish sputum, complicated by mild to moderate hemoptysis, progressive stage 4 dyspnea, and bilateral lower thoracic pain. Additional symptoms included palpitations, headaches, febrile sensations, profound asthenia, unquantified weight loss, and anorexia. Outpatient antibiotic treatment with levofloxacin, followed by amoxicillin–clavulanic acid, yielded no improvement.

Clinical examination revealed profuse sweating, a heart rate of 127 bpm, blood pressure of 170/90 mmHg, respiratory rate of 35 breaths per minute, and a blood oxygen level of 91% on room air. Signs of respiratory distress included intercostal and suprasternal retractions. Crackles were audible in the lower two-thirds of both lungs, with dullness to percussion at both lung bases. Bilateral lower limb edema was present, soft, and pitting.

Thoracic CT imaging demonstrated multiple nodules and micronodules in both lungs, predominantly on the right, with confluent, well-defined opacities exhibiting a ground-glass appearance. Diffuse thickening of the interlobular septa was observed in both lungs, more prominent in the apical regions, along with a left pleural effusion enhanced by contrast injection, suggestive of empyema. Acid-fast bacilli in sputum were negative, the tuberculin skin test was positive at 12 mm, and the GeneXpert MTB/RIF assay on sputum was positive for Mycobacterium tuberculosis (Fig. 1, Fig. 2).

Fig. 1.

(A) Contrast-enhanced axial chest CT (lung window) demonstrates a loculated left pleural effusion with marked thickening and enhancement of the parietal pleura (arrows), forming a pleural split sign consistent with empyema. Adjacent compression of the underlying lung parenchyma is noted. (B) Axial chest CT (lung window) shows bilateral pulmonary consolidations, predominantly peripheral, with a ring-like appearance in the right lower lobe (arrow), associated with a left-sided loculated pleural effusion consistent with empyema. (C) Axial chest CT (lung window) demonstrates a right apical alveolar consolidation with visible air bronchogram (arrow), consistent with active infectious parenchymal involvement.

Fig. 2.

(A) Contrast-enhanced axial abdominal CT demonstrates a well-circumscribed right adrenal mass (arrow) with heterogeneous internal architecture and intense contrast enhancement. (B) Delayed contrast-enhanced axial CT image shows persistent enhancement of the right adrenal mass (arrow), indicating slow contrast washout, a characteristic feature of hypervascular adrenal tumors.

Given the presence of high blood pressure and profuse sweating, a renal artery Doppler ultrasound was performed, revealing a right adrenal mass suggestive of pheochromocytoma. Further evaluation with an abdominal CT scan using a standard triphasic protocol (unenhanced, portal venous at 70 seconds, and delayed at 15 minutes) demonstrated a round tumorous lesion measuring 55 × 33 mm² involving the lateral limb of the right adrenal gland and infiltrating the upper pole of the right kidney, consistent with pheochromocytoma. The diagnosis was confirmed by elevated catecholamine metabolites: normetanephrine > 4500 nmol/24 h (reference range: 75-375 µg/24 h) and 3-methoxytyramine = 2403 nmol/24 h (reference range: < 300 µg/24 h).

To further investigate the peripheral edema, a 24-hour proteinuria test was performed and was positive at 4 g/L. Autoimmune markers (ANCA, ANA, and anti-GBM antibodies) were negative. Renal biopsy confirmed minimal glomerular lesions with focal segmental glomerulosclerosis.

Cardiac evaluation revealed left heart failure with left ventricular hypertrophy, a reduced left ventricular ejection fraction of 21%, and a partial thrombosis of the inferior vena cava.

The patient’s clinical course was complicated by hemodynamic instability, worsening dyspnea, and severe cardiac arrhythmias, ultimately resulting in death despite appropriate supportive care.

Discussion

The coexistence of hemoptysis, severe hypertension, and multisystem involvement presented a significant diagnostic challenge. In this case, confirmation of pulmonary tuberculosis led to the interpretation of systemic manifestations and hemoptysis as infection-related, which delayed recognition of an alternative endocrine etiology despite severe hypertension and multiorgan dysfunction.

Pheochromocytomas are catecholamine-producing adrenal gland tumors originating from the sympathetic adrenal medullary chromaffin tissue. They are often referred to as the “Great Masquerader” because of their highly variable and frequently atypical clinical presentations. The incidence is estimated at approximately 0.6-0.8 cases per 100,000 person-years, and symptoms occur in only about 50% of patients, typically in a paroxysmal manner [3,4]. The classic triad of headache, sweating, and palpitations is observed in only 24% of cases [3,4]. Genetically, pheochromocytomas may be either sporadic or hereditary, the latter being transmitted in an autosomal dominant fashion. Approximately 70% of pheochromocytomas belong to 1 of 3 molecular clusters, each associated with distinct phenotypes, clinical behavior, and radiological characteristics [[3], [4], [5]].

Cardiac dysfunction is a recognized and potentially fatal complication of pheochromocytoma, resulting from catecholamine-induced myocardial injury. This condition may manifest as diffuse left ventricular involvement, severe systolic dysfunction, myocardial edema, and elevated cardiac troponin levels, potentially leading to irreversible myocardial damage and remodeling. Other reported cardiac complications include dilated cardiomyopathy, Takotsubo syndrome (both classic and reverse), hypertrophic obstructive cardiomyopathy, and myocarditis [5,6]. In our patient, cardiac evaluation revealed left heart failure with left ventricular hypertrophy, a markedly reduced left ventricular ejection fraction of 21%, and partial thrombosis of the inferior vena cava. In severe cases, adrenergic crises triggered by pheochromocytoma may mimic acute coronary syndrome or result in multiorgan failure [5,6].

Pulmonary manifestations of pheochromocytoma are uncommon. Hemoptysis, in particular, is a rare presentation and may result from severe systemic hypertension leading to pulmonary venous hypertension, pulmonary edema, and diffuse alveolar hemorrhage. Additionally, excessive catecholamine secretion may induce vascular injury and activation of the coagulation cascade [1]. Several cases in the literature have described this atypical presentation. One report described a 37-year-old patient presenting with sudden-onset cough, dyspnea, and significant hemoptysis associated with low ejection fraction and proteinuria, subsequently diagnosed with pheochromocytoma [1]. Another case reported hemoptysis and left ventricular dysfunction that resolved after surgical removal of the tumor [7]. Similar presentations with dyspnea and hemoptysis associated with severe hypertension and cardiac failure have been reported and later confirmed biochemically and radiologically as pheochromocytoma [8,9]. Although rare, pulmonary hemorrhage may represent a severe manifestation of catecholamine-secreting tumors, and delayed diagnosis or treatment can lead to fatal complications [8,9].

Renal involvement may further complicate the clinical presentation of pheochromocytoma. The coexistence of nephrotic syndrome and pheochromocytoma is exceedingly rare. Tirri et al. [10] reported a case of a young woman with left adrenal pheochromocytoma associated with nephrotic syndrome, proposing immunological mechanisms or glomerular hyperfiltration as possible pathogenic explanations. Therefore, hemoptysis, cardiac failure, and proteinuria should be considered potential presenting manifestations of pheochromocytoma, particularly in patients with severe paroxysmal hypertension [10]. In contrast to these reports, this patient presented simultaneously with severe cardiac dysfunction, pulmonary hemorrhagic manifestations, renal involvement, and confirmed pulmonary tuberculosis, making the diagnosis particularly challenging.

Diagnostic imaging played a central role in this case, both as a source of diagnostic confusion and as a decisive element in narrowing the differential diagnosis. Thoracic CT demonstrated bilateral nodules and micronodules with confluent ground-glass opacities, associated with diffuse interlobular septal thickening and a contrast-enhancing pleural effusion. In a tuberculosis-endemic context, this radiological pattern initially favored an infectious etiology, particularly active pulmonary tuberculosis. However, the atypical distribution and severity of pulmonary findings, combined with unexplained severe hypertension and adrenal imaging abnormalities, prompted further investigation beyond an infectious diagnosis. Conversely, abdominal imaging proved crucial, revealing a large, heterogeneous adrenal mass with renal extension, findings incompatible with a benign adrenal adenoma and strongly suggestive of pheochromocytoma. Taken together, thoracic and abdominal imaging supported the presence of dual pathology and underscored the importance of comprehensive imaging assessment in distinguishing infectious from endocrine-related pulmonary manifestations.

Contrast-enhanced abdominal computed tomography remains the initial imaging modality of choice for suspected pheochromocytoma, as approximately 95% of tumors are adrenal in origin. CT offers a sensitivity ranging from 98% to 100%, with attenuation values greater than 10 Hounsfield units and delayed contrast washout being highly suggestive features. Magnetic resonance imaging is particularly valuable for detecting extra-adrenal, residual, recurrent, or metastatic disease and is preferred in patients with contraindications to iodinated contrast or when radiation exposure must be limited [5].

The occurrence of pulmonary tuberculosis in this patient can be attributed primarily to epidemiological factors, as Morocco is a tuberculosis-endemic area. According to the World Health Organization, the estimated incidence in 2021 was 35,000 cases, corresponding to a rate of 94 per 100,000 inhabitants [11]. In this context, general symptoms, such as weight loss, night sweats, and hemoptysis, were initially attributed to tuberculosis, contributing to delayed recognition of the underlying pheochromocytoma. This diagnostic puzzle arose from the coincidental association of tuberculosis and pheochromocytoma in an endemic region, which could explain the same symptoms. This condition remains rare, with only a limited number of cases reported in the literature [[12], [13], [14]].

Conclusion

The diverse clinical presentation of pheochromocytoma often mimics other conditions, leading to diagnostic confusion. Although the association of pheochromocytoma and pulmonary tuberculosis is rare, this unusual co-presentation serves as a strong reminder: The diagnosis of pheochromocytoma should not be dismissed in patients presenting with a complex triad of uncommon hemoptysis, hypertension, and heart failure, even if tuberculosis is confirmed.

Patient consent

Consent was obtained, and the patient’s family members were informed of all written information regarding this medical case.