Plasma methoxytyramine: a novel biomarker of metastatic phaeochromocytoma and paraganglioma in relation to established risk factors of tumour size, location and succinate dehydrogenase B mutation status Eisenhofer G, Lenders JWM, Siegert G, et al. European Journal of Cancer 2011, published online 31st October 2011 ahead of print; doi:10.1016/j.ejca.2011.07.016The World Health Organization defines phaeochromocytoma as a tumour arising from catecholamine-producing chromaffin cells in the adrenal medulla. Closely related tumours of extra-adrenal sympathetic (catecholamine producing) and parasympathetic (rarely catecholamine producing) paraganglia are classified as extra-adrenal paragangliomas (PPGLs). The metastatic potential of these neuroendocrine tumours is variable and currently there are no reliable biomarkers.Eisenhofer et al. report in a large, well-characterized cohort (365 patients with PPGLs, including 105 with metastasis and a reference population of 846 without a tumour) on the utility of measuring 18 catecholamines (including plasma and urine noradrenaline, adrenaline, dopamine and 3,4-dihydroxyphenylalanine and their respective free and conjugated O-methylated metabolites) in relation to tumour size, location and succinate dehydrogenase B (SDHB) mutation status, in the assessment of metastatic phaeochromocytoma and PPGL.Plasma 3-methoxytyramine (3-MT), the O-methylated metabolite of dopamine, was found to be 4.7-fold higher in patients with than without metastases; this was independent of tumour burden. Receiver operating characteristic curve analysis showed that 3-MT was the best biomarker for distinguishing between patients with and without metastases (area under the curve [AUC] ¼ 0.716, P, 0.0001); normetanephrine, in contrast, showed a lack of discriminatory power (AUC ¼ 0.547, P¼ 0.171). Plasma 3-MT was also shown to be a more sensitive biomarker of tumoural dopamine production than either plasma or urinary dopamine.Data showed that plasma 3-MT had an association with extra-adrenal primary tumours (plasma 3-MT concentration 274% higher [P, 0.001] than those with adrenal tumours) and SDHB mutation. However, plasma 3-MT concentration was also increased in patients with metastases without SDHB mutations and those with metastases secondary to adrenal tumours. A plasma 3-MT .200 pmol/L or a tumour .5 cm in diameter increased the likelihood of metastatic spread, especially in those patients with extra-adrenal tumours.The authors concluded that plasma free 3-MT is a novel biomarker for metastatic PPGLs and that together with knowledge of SDHB mutation status, tumour size and location, it can aid in assessing the likelihood of malignancy and clinical management of patients with PPGLs. Nephrolithiasis in children is increasing in prevalence and tends to be recurrent. In adults, recognized risk factors for stone formation include familial hypercalciuria, hyperoxaluria, hypocitraturia, low urine volume and hyperuricosuria. Few studies have looked at risk factors in stone-forming children and compared them t...