Keywords

Hypertensive emergency, pheochromocytoma, secondary hypertension, recurrent cerebrovascular disease Pheochromocytoma is a tumor of the sympathetic or parasympathetic nervous system and is one of the causes of secondary hypertension, which is refractory to antihypertensive therapy. This is a curable cause of hypertension and its early detection and diagnosis is equally important.

Case ReportChief Complaints

Mr Suresh, a 22-year-old male was admitted to the hospital with chief complaints of: a) Inability to use both his left upper and lower limbs for 3 days; b) inability to speak; c) deviation of angle of mouth to the right side; d) double vision and e) recurrent episodes of headache, palpitation and sweating. There was history of similar episode 2 years ago. He also had history of one episode of seizure 7 years before. On examination, his blood pressure (BP) was 220/120 mmHg and pulse rate was 120/min. Cardiovascular system, respiratory rate and per abdomen examination revealed no abnormalities. On neurological examination, he had left-sided hemiplegia, horizontal nystagmus with lateral gaze, left-sided 3rd nerve palsy, right-sided 6th nerve palsy and right-sided lower motor neuron type of facial palsy and cerebellar signs.

InvestigationsBlood Investigations

1. Hemoglobin 13.2 g/dL, total leukocyte count 5,000 cells/mm3, differential leukocyte count P62L34E4, erythrocyte sedimentation rate 16 mm/hour.
2. Urea 35 mg/dL, creatinine 1 mg/dL, Na+ 134.1 mEq/L Cl- 85.2 mEq/dL, K+ 3.1 mEq/dL.
3. Total cholesterol 138 mg/dL, triglycerides 119 mg/dL, high-density lipoprotein 38 mg/dL, low-density lipoprotein 76 mg/dL, very low-density lipoprotein 24 mg/dL. Cholesterol ratio 3.6.
4. Antiphospholipid antibody 6.67 U/mL. ÂÂ 24-hour urinary vanillylmandelic acid (VMA)18.88 mg/24 hours (normal value <6-8 mg/dL in adults).

ECG

Sinus tachycardia, electrical left atrial enlargement/left ventricular hypertrophy.

Chest X-ray

Normal

MRI Abdomen

Multiple relatively defined discrete lesions of varying sizes noted in the bilateral para-aortic region, extraadrenal pheochromocytoma, shrunken right kidney.

CT BrainMultiple infarcts.

Course in Hospital

He was admitted to the intensive care unit (ICU) with a BP of 220/120 mmHg and nitroglycerin (NTG) infusion was started to control his BP. There was a very irregular response. NTG infusion was gradually tapered and he was put on prazosin, calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors. Later, he was put on phenoxybenzamine, starting with 10 mg b.i.d. and increased to 20 mg t.i.d. After that, a b-blocker was added to control the tachycardia. He was advised low salt diet and adequate hydration. His BP was gradually reduced from 180/130-150/90 mmHg with episodes of wide fluctuations. After his BP was consistently below 160/90 mmHg for 2 weeks, he was taken up for surgery. Laparotomy was done and multiple tumors were excised from the bilateral para-aortic region. There was an intraoperative rise in the BP associated with handling of the tumors, which was brought to control by NTG infusion. A small portion of the tumor near the left renal vein was left behind because of difficulty in removing it without damaging the left renal artery. Postoperatively, the BP increased to 220/130 mmHg, which was managed by NTG infusion and magnesium sulfate regime. His BP was stabilized to 130/100 mmHg within a week and was discharged with methyldopa 250 mg b.i.d. and vitamins. During follow-up, his BP was found to be within normal limits.

Histopathological Examination

Specimen: Extra-adrenal pheochromocytoma. Gross: Several fragmented dark brown masses in aggregates of size 7 × 4 × 3 cm. The cut surface showed a dark yellow to orange nodular lesion with a thin rim at the periphery.Microscopy: Revealed small nesting growth pattern (zellballen appearance). Tumor cells were fairly uniform with finely granular cytoplasm.Diagnosis: Extra-adrenal mass, excision-pheochromocytoma.

Discussion

The patient was a young hypertensive who developed crossed hemiplegia due to brainstem lesion. Computed tomography (CT) brain showed multiple infarcts, which were secondary to hypertension. Urinary VMA was elevated and magnetic resonance imaging (MRI) abdomen showed multiple extra-adrenal masses. BP was refractory to antihypertensive therapy. Patient was put on a- and b-blockers, ACE inhibitor, methyldopa. Inspite of these drugs, his BP did not come under control. Metaiodobenzylguanidine (MIBG) scan could not be done because the patient could not afford it. Bilateral multiple extra-adrenal paraganglion masses were excised.

In the postoperative period, BP started to come down and on follow-up, his BP was normal.

1. About 10% pheochromocytomas are extra-adrenal and most of them are <10 cm in diameter.
2. It manifests as hypertension, which responds paradoxically to antihypertensive therapy.
3. Patients have paroxysms during which they develop headache, sweating and palpitations.
4. Cardiac manifestations are supraventricular tachycardia, ventricular arrhythmias, angina and cardiomyopathy.
5. Some patients present with acute respiratory distress syndrome.
6. There are reports of pheochromocytomas presenting as panic attacks, pre-eclampsia, impaired glucose tolerance and pulmonary edema.

Biochemical assessment are done for urinary VMA, homovanillic acid, fractionated metanephrines and catecholamines.

1. Plasma catecholamines, dopamine, free metanephrines (most sensitive) and chromogranin A may also be assayed.
2. MRI/CT of the abdomen and MIBG scan help to localize the tumor.
3. Patients should also be evaluated for other associated syndromes like multiple endocrine neoplasia 2A/2B, Von Hippel-Landau syndrome, neurofibromatosis, familial paraganglioma, familial pheochromocytoma with islet cell tumor, Sturge-Weber syndrome, ataxia telangiectasia, tuberous sclerosis and Carney’s triad.

ConclusionThis case is being presented as a young hypertensive with recurrent cerebrovascular accident (CVA) and seizures who had resistant hypertension not amenable to antihypertensive therapy given in high dosage in different combinations. Urinary VMA was positive and further investigations confirmed pheochromocytoma. Surgical removal brought complete cure to the patient. Pheochromocytoma presenting as recurrent CVA is a very rare and unusual manifestation of the tumor.

Suggested Reading

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10. d’Herbomez M, Gouze V, Huglo D, Nocaudie M, Pattou F, Proye C, et al. Chromogranin A assay and (131) I-MIBG scintigraphy for diagnosis and follow-up of pheochromocytoma. J Nucl Med. 2001;42(7):993-7.