medwireNews: Plasma and urine analyses are both reliable screening tests for the diagnosis of phaeochromocytoma/paraganglioma (PPGL) in children and adolescents, report researchers in Clinical Endocrinology.
While the previously published prospective PMT trial showed that the measurement of plasma free metanephrines (metadrenalines) is superior to that of urinary metabolites for the diagnosis of PPGL in adults, few studies have compared the approaches in a paediatric population, explain Christina Pamporaki (University Hospital Carl Gustav Carus, Dresden, Germany) and co-authors.
To investigate further, the team conducted a retrospective cohort study involving 138 patients aged 5–18 years between 1998 and 2020, 64 of whom had a confirmed diagnosis of PPGL. All patients had plasma measurements of free metanephrines and genetic test findings, and 89 of the children also had 24-hour urinary fractionated metanephrine results.
Most children with (69%) and without (78%) a diagnosis of PPGL were participating in a surveillance programme due to having a hereditary risk or prior diagnosis rather than signs and symptoms. Genetic testing showed that 84% and 70% of patients with and without PPGL, respectively, had Cluster 1 germline pathogenic variants (PVs) linked to norepinephrine production (VHL, SDHB, SDHC, SDHD and HIF2A), while a corresponding 3% and 4% had Cluster 2 PVs in RET or NF1 that are associated with excess epinephrine.
Pamporaki et al report that plasma metanephrines and urinary metabolites were both 92% sensitive for PPGL and a comparable 96% and 91% specific, respectively, indicating that both approaches are “reliable and robust tests for diagnosis of PPGL in children and adolescents.”
However, children with PPGL had a significantly greater increase in plasma normetanephrine levels above the upper cut off than for 24-hour urinary metabolites, at 9.5-fold versus 7.1-fold. There were no increases above the upper cutoff observed for metanephrines with either test.
The researchers also examined temporal measurements of plasma metabolites in nine children who participated in a surveillance programme for 2–7 years and had at least three measurements taken at screening intervals of 5–15 months.
They found that the average 6-month percentage increase in plasma free normetanephrine was significantly higher in the five children who were subsequently diagnosed with PPGL than in the four who were not (46.6 vs 5.5%), with increases detected in every child at their last blood test before diagnosis. By contrast, there was no significant difference in plasma free metanephrine levels in the children with or without PPGL.
“Importantly, our study provides preliminary elements that the plasma panel may be a useful test for the detection of early stage noradrenergic/dopaminergic PPGL in children under surveillance programs either due to PVs of Cluster 1 genes or previous history of noradrenergic tumours”, say Pamporaki and co-authors.
They emphasize that plasma testing may be “particularly relevant” to these children because they are at higher risk of metastatic disease and most likely to benefit from early detection.
“[F]or the rare group of children at surveillance due to PVs of Cluster 2 genes, who are at risk of developing adrenergic tumours with very low metastatic potential, urinary testing is an equally good alternative, and the choice of urine vs plasma test could be guided by availability, experience, and practical considerations”, the researchers add.
They conclude that their “findings are expected to guide further individualized management and follow-up strategies of children tested for PPGL.”
By Lynda Williams
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