Atypical presentation of pheochromocytoma: Central nervous system pseudovasculitis.

Pheochromocytoma has atypical presentation in 9%-10% of patients. Atypical presentations include myocardial infarction, renal failure, and rarely cerebrovascular events. Various etiologies for central nervous system (CNS) involvement in pheochromocytoma have been described in the literature. A rare association of CNS vasculitis-like features has been described with pheochromocytoma. We report a rare case of pheochromocytoma detected on evaluation for CNS vasculitis-like symptoms.

INTRODUCTION

Pheochromocytoma is a relatively rare neoplasm, with annual incidence of approximately 2–8 million person-years. The classic triad of symptoms in patients with a pheochromocytoma consists of episodic headache, sweating, and tachycardia.[1] Rarely, pheochromocytomas present with cerebrovascular events. Catecholamine-induced central nervous system (CNS) vasculitis has been recognized as one of the rare manifestations in pheochromocytoma. Pheochromocytoma should be included in the differential diagnosis of angiographic findings mimicking CNS vasculitis. We present a case with this unlikely presentation and the subsequent diagnostic evaluation.

CASE REPORT

A 47-year-old female presented with complaints of acute onset severe headache with nausea, vertigo, and gradually progressive weakness of the limbs (upper limb more than lower limb). There were no history of fever, seizures, loss of consciousness, and loss of vision. On examination, the patient was conscious, oriented, and blood pressure was 140/100 mmHg with no tachycardia. Cranial nerve examination was normal. Power in the right and left upper limb was 1/5 while 3/5 in bilateral lower limb. Investigations including complete blood count, renal function tests, coagulation studies, thyroid function test, urinalysis, and chest radiograph were not suggestive of any abnormality. MRI brain revealed multifocal acute infarcts in multiple vascular territories, predominantly in bilateral anterior cerebral arteries territories. Magnetic resonance cerebral angiography showed multifocal multisegmental areas of stenosis involving large- and medium-sized intracranial arteries likely due to CNS vasculitis. Computerized tomography (CT) cerebral angiography of the brain and neck revealed multifocal parenchymal hemorrhages along with areas of hypodensity suggestive of ischemia in the centrum semiovale with narrowing of bilateral terminal internal carotid artery and middle cerebral arteries [Figure 1].

Figure 1

Magnetic resonance imaging of the brain showing multiple areas of acute infarcts with multiple areas of stenosis involving large- and medium-sized arteries. Computerized tomography cerebral angiography revealed narrowing of both internal carotid and middle cerebellar arteries

After identifying cerebral infarction as the cause of the weakness, she underwent detailed evaluation of connective tissue disorders and secondary vasculitis but was noncontributory. The patient was hence diagnosed and treated as primary CNS vasculitis. She was started on prednisolone pulse dosages and later continued on tapering dosages of prednisolone. Significant improvement in power and weakness was noted with steroid with near-normal recovery. She was further planned for cyclophosphamide monthly dosages but found to have grossly deranged liver enzymes. The ultrasonography abdomen during workup of raised liver enzymes revealed the right-sided suprarenal mass which on further evaluation with contrast-enhanced CT scan of the abdomen showed heterogeneously enhancing right adrenal mass measuring approximately 6.9 cm × 5.6 cm × 6.8 cm with calcification and areas of necrosis and possibility of adrenal carcinoma was kept. The mass was closely abutting the intrahepatic inferior vena cava with imperceptible intervening fat planes [Figure 2].

Figure 2

Computerized tomography of the abdomen revealed a heterogeneously enhancing mass measuring 6.9 cm × 5.6 cm × 6.8 cm arising from the right adrenal gland with multiple areas of calcification and necrosis

Functional evaluation of adrenal mass revealed raised metanephrine level. After adequate preoperative preparation in conjunction with an endocrinologist, she underwent right robotic adrenalectomy. Intraoperatively, a 7 cm tumor was found arising from the right adrenal, displacing the right kidney downward and was densely adherant to the liver. The postoperative period was uneventful and the patient was discharged in a stable condition on the 3rd postoperative day. Histopathology revealed pheochromocytoma with clear margins. During follow-up, she had normal power in all the limbs. After 6 months, CT angiography of the brain showed multifocal chronic infarcts seen in bilateral centrum semiovale, right basifrontal region, and left posterior parietal region with normal brain vessels. The patient is doing fine at 1-year follow-up.

DISCUSSION

The clinical presentation of pheochromocytoma is mainly attributable to the excessive secretion of catecholamines.[1] Approximately 91% of pheochromocytoma patients present with typical symptoms such as episodic palpitation, hypertension, headache, diaphoresis, flushing, and dyspnea. The remaining 9%–10% present with atypical symptoms such as weakness, chest pain, paralysis, or claudication. Atypical CNS symptoms are mainly due to cerebral ischemia. Cerebral ischemia leading to neurological features is a rare manifestation of pheochromocytoma. It may lead to acute cerebrovascular event. Various factors considered responsible for cerebral ischemia include severe hypertension with deranged cerebrovascular autoregulation, catecholamine-induced vasospasm of cerebral vessels or catecholamine-induced cardiomyopathy, hypokinesia, and embolization from a left ventricular thrombus. Rarely, pheochromocytoma has been reported to be associated with two distinct types of pathological associations leading to CNS symptoms, reversible cerebral vasoconstriction syndrome, and vasculitis.[234] Razavi et al. reported a case of 34-year-old woman with recurrent palpitations, nausea, diaphoresis, and headache which on evaluation had CNS vessel caliber variation resembling vasculitis. The findings resolved following adrenalectomy. Their patient showed rapid and complete resolution of the angiographic changes without immunosuppressive therapy suggesting pseudovasculitis (and not the primary CNS vasculitis) as the cause of symptoms.[3] Shamsuddin et al. reported case of 51-year-old female presented with acute onset of dysarthria and hemiparesis which on evaluation found to have pheochromocytoma. The potential cause for neurological symptoms was attributed to hypertension and vasospasm.[5] Dagartzikas et al. reported facial palsy with CNS involvement with pheochromocytoma.[6]

Management of cerebrovascular manifestations in pheochromocytoma is primarily based on the control of excessive catecholamine release. Definitive treatment of pheochromocytoma is surgical removal after control of blood pressure and intravascular fluid volume optimization. In our patient, the clinical presentation and imaging findings of CNS vasculitis-like features initially led the treating neurologist to start immunosuppressive therapy. However, further workup led to the detection of a large pheochromocytoma. The patient had a complete and lasting improvement after adrenalectomy.

CONCLUSION

Pheochromocytomas may be associated with rare vascular abnormalities. Although vasculitis-like features as presenting features are very rare, knowledge of atypical presentations of this tumor is imperative. Timely diagnosis is required for optimal management of these atypical conditions.