Clonidine suppression test for pheochromocytoma: examples of misleading results

Baseline plasma norepinephrine (NE) and epinephrine (E) levels over 2000 pg/ml or failure to suppress to less than 500 pg/ml after oral clonidine have been considered diagnostic of the presence of a pheochromocytoma. We found a false negative clonidine suppression test in a patient with an asymptomatic ACTH-secreting pheochromocytoma who had minimally increased resting plasma NE and E values of 669 and 419 pg/ml, respectively. Clonidine suppression caused decreases at 2 and 3 h to 372 and 408 pg/ml, respectively. A positive test was found in a patient with repeatedly elevated baseline plasma NE and E concentrations; the two highest results were 2501 and 3022 pg/ml. Clonidine administration on five occasions failed to decrease plasma NE and E levels to less than 500 pg/ml. However, no pheochromocytoma was found by selective venous catheterization, two laparotomies, and, ultimately, postmortem examination. Diffuse infiltration of lymphoplasmacytic cells throughout sympathetic ganglia and adrenal medulla raise the possibility of a diffuse autoimmune disorder, resulting in excessive catecholamine production. These examples suggest that the clonidine suppression test does not always indicate the presence or absence of a pheochromocytoma.