Objective: The diagnosis of pheochromocytoma/paraganglioma (PPGL) involves detection of elevated levels of plasma and/or 24-h urine catecholamines and/or their metabolites, including metanephrines. Although these tests are reasonably sensitive, false-positive results are often encountered. Follow-up tests can provide additional information to correctly diagnose PPGL. In this regard, the utility of the urinary clonidine suppression test (UCST) remains unknown.
Methods: To assess the diagnostic accuracy of the UCST in confirming or excluding PPGL, we conducted a retrospective analysis of all patients who underwent a UCST between 2000 and 2013 (n = 59; 15 PPGLs) at a single centre. Twelve-hour urine catecholamines and metanephrines were assessed before and after clonidine administration, and examined in relation to final diagnosis, PPGL or non-PPGL. Receiver operating characteristic analyses were used to identify optimal positivity cut-offs. Sensitivity, specificity, positive and negative predictive values were calculated.
Results: Clonidine significantly decreased urine creatinine-corrected norepinephrine and normetanephrine in patients without PPGL (P < 0.001 pairwise) but not in patients with PPGL. Epinephrine and metanephrine levels were not significantly reduced in either group. Receiver operating characteristic (ROC) area under the curve was 0.955 [95% confidence interval (95% CI) 0.906-1.000, P < 0.001] and 0.823 (95% CI 0.706-0.940, P < 0.001) for norepinephrine and normetanephrine, respectively. Optimal cut-offs were established at 50 and 15% reductions in norepinephrine and normetanephrine, respectively, which provided high sensitivities (93.3% for both) and negative predictive values (97.4 and 96.3%). When both were concordant, higher diagnostic accuracy was achieved (100% sensitivity, 92.0% specificity). Results were similar in subgroups of individuals with borderline initial testing (n = 40) or on interfering drugs (n = 25).
Conclusion: The UCST appears to be a highly accurate test for PPGL. Further prospective studies are needed to validate these results before routine use is encouraged.