A pheochromocytoma with normal clonidine-suppression test: how difficult the biochemical diagnosis?

Pheochromocytomas are rare but clinically important tumors of chromaffin cells that take up, produce, store, release, and metabolize catecholamines, and constitute a potentially surgically curable cause of hypertension [1]. Failure to diagnose the tumor can result in devastating consequences. The diagnosis of pheochromocytoma depends crucially on the biochemical evidence of catecholamine production by the tumor [2]. The clonidinesuppression test is widely used for distinguishing high plasma catecholamine levels caused by increased sympathetic nervous system outflows from high levels caused by a high rate of secretion by a pheochromocytoma [3]. We report the case of a 50-year-old white man referred to the Padua hypertension unit for the clinical evaluation of hypertension and adrenal mass with increased urinary metanephrines and negative clonidine-suppression test. The patient was a heavy smoker; his LDL cholesterol was 162 mg/dL. Blood pressure had not been measured in the last 3 years. One month before, he had been admitted to another hospital for abdominal pain and vomits. Arterial blood pressure was 200/102 mmHg with heart rate of 72 beats/min. Abdomen radiograph was negative. Results of initial laboratory tests were significant for a troponin I level of 4.0 lg/L (normal range, \0.1 lg/L). Serum chemistry and complete blood count were also normal or non-contributory. Electrocardiography showed 2-mm ST-segment depression in leads V1, V2 and V3. At echocardiographic examination, left ventricular ejection fraction was 60% and left ventricle concentric hypertrophy present. Since he complained of several episodes of abdominal pain associated with nausea and vomits, he underwent an abdominal computed tomography that showed a right adrenal mass of 2.5 cm 9 3 cm. Plasma renin, serum aldosterone, serum and urinary corisol, and 24-h urinary excretion rates of catecholamines were described as normal. Upon discharge he was on amlodipine 10 mg o.d., pravastatin 40 mg o.d., acetylsalicylic acid 100 mg o.d., and trans-dermal nitroglycerine. The patients quitted to smoke and he was referred to our unit for adrenal mass and hypertension. Arterial blood pressure was persistently elevated (Table 1). Twenty-four hours non-invasive ambulatory blood pressure was 136/79 mmHg, with several peaks of systolic blood pressure, the highest reaching 198 mmHg. Repeated 24-h urinary excretion rates of catecholamines were non-contributory, as were plasma aldosterone, plasma and urinary cortisol, within the normal range (Table 2). Plasma renin activity, plasma concentration of norepinephrine and epinephrine were slightly elevated (Table 2). Urinary levels of metanephrines and plasma chromogranin A were above our normal cut-off (Table 2). Urinary normethanephrines and methanephrines were elevated beyond four-fold of normal cut-off, and were diagnostic of pheochromocytoma. A clonidine-suppression test was, also, carried out after an overnight fast in supine position. The patient was instructed to abstain from caffeinated and decaffeinated beverages and to avoid taking acetaminophen for 5 days before blood sampling. A baseline blood sample was drawn into a 10-ml heparinized tube through a M. Sartori (&) Department of Angiology and Blood Coagulation ‘Marino Golinelli’, University Hospital S. Orsola-Malpighi, Via Albertoni, 15, 40138 Bologna, Italy e-mail: michelangelo.sartori@aosp.bo.it