Plasma levels of free metanephrines and 3-methoxytyramine indicate a higher number of biochemically active HNPGL than 24-h urinary excretion rates of catecholamines and metabolites

A substantial number of patients with head and neck paragangliomas (HNPGLs) have biochemically active tumors, evidenced by increased urinary excretion of catecholamines and metabolites, including 3-methoxytyramine (3MT). It is unclear whether plasma levels of these parameters are more sensitive to detect biochemical activity in HNPGL patients than urinary excretion rates. To compare plasma free levels vs urinary excretion rates of deconjugated 3MT and combined metanephrines (MNs) in patients with HNPGL. We included 124 consecutive patients with HNPGL for screening of catecholamine excess by measurement of 24-h urinary excretion rates of deconjugated (nor)metanephrine, (nor)epinephrine, dopamine, vanillylmandelic acid, 3MT, and plasma free levels of (nor)metanephrine and 3MT. Plasma free 3MT levels were increased in 35 of the 124 patients (28%), whereas 24-h urinary excretion of deconjugated 3MT was increased in 30 patients (24%) (P=0.13). Plasma free MN levels were increased in seven patients (6%) and urinary deconjugated MN levels in six patients (5%) (P=1.00). Plasma free normetanephrine (NMN) levels were increased in seven patients (6%), and five patients had increased urinary excretion of deconjugated NMN (4%) (P=0.69). Plasma free combined MN levels (NMN, MN, and 3MT) were increased in 41 patients (33%), whereas 24-h urinary excretion rates of deconjugated combined MNs were increased in 33 patients (27%, P <0.05). The combined levels of free MNs and free 3MT in plasma indicate a higher number of biochemically active HNPGLs than the 24-h urinary excretion rates of these markers