Diagnosis of pheochromocytoma

Abstract

Sir, Pheochromocytoma is a rare tumor of chromaffin cells accounting for less than 0.3% of all cases of hypertension. Majority of them are benign and are a surgically curable cause of hypertension. Aggressive diagnostics and surgical intervention are recommended because failure to diagnose the tumor can result in uncontrolled catecholamines release leading to catastrophic consequences.[1] Many biochemical diagnostic tests and imaging modalities exist for diagnosis and localization of tumor; however, optimum approach remains debatable. A 21-kg, 11-year-old boy presented with a history of hypertension, occasional headache, vomiting, and perspiration since 2 months. His pulse rate was 110/min and blood pressure 150/106 mm of Hg. Electrocardiogram was suggestive of left ventricular hypertrophy (LVH). On ultrasound examination a 2.9 × 2.7 cm mass was seen at renal hilar region. Contrast computed tomography (CT) scan showed a 3.7 × 2.6 × 2.5 cm hypodense well-defined enhancing mass lesion with nonenhancing central cystic lesion near the left renal hilum medially. Left adrenal gland was seen to be separate from the mass lesion, suggesting a retroperitoneal mass, possibly an extra-adrenal pheochromecytoma. Urinary vanillyl-mandelic-acid (VMA) and urinary total metanephrines, estimated by column chromatography, were 6.35 mg/24 h (normal - 1.90 to 13.60) and 0.59 mg/24 h (normal – 0.00 to 0.90), respectively. All hematological investigations were within normal limits. In view of negative biochemical test results and possibility of extra-adrenal pheochromocytoma, Iodine 131 labeled meta-iodo-benzyl-guanidine (131I MIBG) scan was performed which suggested negative result. The preoperative 2D echocardiography suggested LVH with ejection fraction (EF) 50%. Fundus examination showed grade IV hypertensive retinopathy. With a provisional diagnosis of extra-adrenal pheochromocytoma, oral phenoxybenzamine 10 mg thrice a day was started and gradually increased up to 40 mg thrice a day. Oral propranolol (20 mg) thrice a day was started after 4 days to control heart rate. After 10 days of preoperative preparation, patient was subjected to retroperitoneal laparoscopic removal of tumor. The tumor was found to be arising from adrenal gland and extending up to the renal hilum. Histopathological examination confirmed the diagnosis of pheochromocytoma. This case raises several questions related to reliability of tests used for the diagnosis and localization of pheochromocytoma. The diagnosis of pheochromocytoma depends on demonstration of excessive production of catecholamines or its metabolites in urine or plasma. 24 h urine tests are considered superior to plasma tests mainly because tumor often secrete catecholamines intermittently and the short half-life of catecholamines can result in relatively normal plasma catecholamine levels even in the presence of a functional tumor. Measurement of VMA in urine is relatively inexpensive, easy to perform, and although it has acceptable specificity (95%), it has a low sensitivity (64%). Urinary total metanephrines has a similar specificity but higher sensitivity (77%) and several studies have found it to be the most sensitive test for the diagnosis of pheochromocytoma. All these biochemical tests were negative in spite of a clinically active tumor in the patient. The amounts of unmetabolized catecholamines or metabolic products released from tumor were possibly not high enough to provide abnormal urinary values, although they were sufficient to provoke the typical symptomatology. Measurement of free metanephrines in plasma has emerged as promising and reliable initial test in the diagnosis of pheochromocytoma compared to conventional tests with sensitivity of 99% and specificity of 89%.[23] Plasma-free metanephrines are produced continuously by metabolism of catecholamines within pheochromocytoma tumor cells and are relatively unaffected by sympathoadrenal excitation. In contrast VMA and the total metanephrines measured in urine are produced in different parts of the body by metabolic processes not directly related to the tumor itself. MIBG offers an approach to overcome the limitations of anatomic imaging. The diagnostic specificity of MIBG has been reported close to 100%[45] as it is concentrated, released, and stored in the chromaffin granules; however, it was negative in our case probably due to necrotic lesion suggestive on CT scan. CT and magnetic resonance imaging (MRI) are believed to be the best-available anatomic imaging techniques and choice depends on institutional preference. Both imaging studies have excellent sensitivity but lack adequate specificity for unequivocally confirming a mass such as a pheochromocytoma. The recent introduction of combined positron emission tomography/CT scanning has emerged as a promising test but is not widely available.