Catecholamine metabolism in paraganglioma and pheochromocytoma: similar tumors in different sites?
Level 4 - case-series / case-control
Cross-sectional comparative human tissue and plasma study with in vitro cell culture experiments.
PubMed 25946206 · doi:10.1371/journal.pone.0125426
What was done
Researchers evaluated the effect of tumor anatomical location on catecholamine metabolism across 66 tissue samples (53 pheochromocytomas [PHEO], 13 paragangliomas [PGL]) and 73 plasma samples (50 PHEO, 23 PGL). Tyrosine hydroxylase (TH), dopamine β-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT) mRNA and protein expressions were quantified using qPCR and Western blot. PHEOs were partitioned into noradrenergic (intra-tumoral norepinephrine/epinephrine ratio > 90%) and mixed tumors. Primary PHEO and PGL cell cultures were also incubated with dexamethasone for 24 hours to test glucocorticoid-mediated enzymatic regulation.
What was found
Initial comparisons showed significantly lower intra-tumoral concentrations of catecholamines and metanephrines, alongside downregulation of TH and PNMT mRNA and protein in PGL compared to unstratified PHEO (no numeric values or p-values reported in the abstract). When PHEOs were partitioned by catecholamine ratio, noradrenergic PHEOs and PGLs exhibited similar TH, DBH, and PNMT gene and protein expression, as well as equivalent catecholamine concentrations and composition. In primary cell culture, 24-hour dexamethasone treatment increased TH mRNA without altering TH protein expression, and caused no changes in DBH or PNMT mRNA or protein in either tumor type.
Why it matters
This study demonstrates that the microenvironmental glucocorticoid milieu of the adrenal gland does not determine long-term catecholamine synthesis in these tumors. It confirms that biochemical catecholamine and metanephrine profiling cannot distinguish noradrenergic pheochromocytomas from extra-adrenal paragangliomas.
Limits
The study is limited by a small sample size for paragangliomas (13 tissue and 23 plasma samples). The abstract does not provide exact numerical values, effect sizes, or confidence intervals for concentrations and gene/protein expression levels. In vitro testing was limited to a single 24-hour dexamethasone exposure.
Cited by
- supports Dopamine, norepinephrine, and epinephrine are catecholamines synthesized biochemically from one another via enzymatic cleavage/modification.