High concentration of plasma methoxytyramine: dopamine-producing tumour or Parkinson's disease therapy?

Background Levodopa (L-DOPA) provided to patients with Parkinson's disease causes an increase in dopamine and methoxytyramine blood concentration which may lead to erroneous diagnosis of dopamine-producing tumours based on a plasma fractionated metanephrines and methoxytyramine assay. Considering that oral L-DOPA is mainly transformed in the gut wall into dopamine and methoxytyramine, we hypothesize that patients treated with L-DOPA produce predominantly sulphated methoxytyramine, whereas dopamine-producing tumours, devoid of sulfotransferase, will secrete free methoxytyramine. These metabolic differences may allow for discrimination between the two groups of patients through methoxytyramine plasma concentration. Methods We retrospectively investigated a cohort of 16 patients with a dopamine-secreting pheochromocytoma or paraganglioma and 22 patients treated for Parkinson's disease to see whether the metabolic ratio of free and sulphated methoxytyramine differs. Results Receiver operating characteristic curve analysis indicates an absolute separation between the two groups when using a cut-off of free/total methoxytyramine (sum of free and sulphated methoxytyramine) ratio of 0.0059, corresponding to a free methoxytyramine fraction of 0.59% (P < 0.0001, AUC 1.0 indicating 100% sensitivity and specificity). Conclusion Dopamine secreted by tumours and exogenous dopamine (from Parkinson's disease treatment) follow different metabolic pathways. We observed that free/total methoxytyramine ratio may be a useful tool in distinguishing between patients with a dopamine-secreting tumour from patients treated with L-DOPA when clinical information is incomplete or lacking.