Urinary clonidine suppression testing for the diagnosis of pheochromocytoma.
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).


CONCLUSIONS
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.
aEndocrine Hypertension Research Centre, University of Queensland School of Medicine, Greenslopes and Princess Alexandra Hospitals, Brisbane, Queensland, Australia (EHRC) bHôpital du Sacré-Coeur de Montréal, University of Montreal, Montreal, Quebec, Canada cClinic of Endocrinology and Diabetes Center, General Hospital of Athens 'G. Gennimatas', Athens, Greece *Both Rémi Goupil and Stelios Fountoulakis contributed equally to this work.
Rémi
R
Goupil
Stelios
S
Fountoulakis
Richard D
RD
Gordon
Michael
M
Stowasser
D000310:Adrenal Gland Neoplasms / Q000175:diagnosis* / Q000652:urine; D000328:Adult; D002395:Catecholamines / Q000652:urine*; D003000:Clonidine; D005260:Female; D006801:Humans; D008297:Male; D008676:Metanephrine / Q000652:urine*; D008875:Middle Aged; D010673:Pheochromocytoma / Q000175:diagnosis* / Q000652:urine; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016482:Urinalysis
D002395:Catecholamines; D008676:Metanephrine; D003000:Clonidine