Urinary clonidine suppression testing for the diagnosis of pheochromocytoma

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.

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.

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).

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.