Diagnosis of pheochromocytoma and paraganglioma: the clonidine suppression test in patients with borderline elevations of plasma free normetanephrine Background: Measurements of plasma free metanephrines provide a sensitive test for the diagnosis of pheochromocytoma/paraganglioma (P/PGL), with highly elevated levels diagnostic of the disease. However, there is less diagnostic certainty in patients with mild elevations of these catecholamine metabolites. Patients and methods: Here we report use of the clonidine suppression test (CST) as a second-tier diagnostic test in 24 patients with mild elevations of plasma free metanephrines and/or catecholamines. Blood samples before and 3 hours after clonidine were analyzed for plasma concentrations of metanephrines and catecholamines with a negative test result defined as either a clonidine-induced fall in normetanephrine or noradrenaline by more than 40 % and 50 % respectively or to below the upper cut-offs of reference intervals. Results: P/PGLs were confirmed in 9 patients and excluded in 15 by independent criteria. More than half of the patients without P/PGL showed normalized plasma concentrations of normetanephrine at baseline before clonidine compared to initial screening; all showed appropriate clonidine-induced falls in normetanephrine and noradrenaline or levels after the drug below upper cut-offs, indicating a diagnostic specificity of 100 % (CI 78-100 %). However, similar responses for noradrenaline were noted in 7 patients with P/PGL, indicating a diagnostic sensitivity of only 22 % (CI 2,8-60 %) compared to 100 % (CI 66-100 %) for normetanephrine. Conclusion: These results support use of the CST in combination with measurements of normetanephrine for confirming or excluding P/PGL in patients with borderline elevated test results, which should, however, first be confirmed by sampling blood under standardized resting conditions.