C-terminal FGF-23 production coupling with aldosterone via FAM20C and predicting cardiovascular events in primary aldosteronism.

Summary

In unilateral primary aldosteronism, circulating cFGF-23 is elevated, tracks nonlinearly with aldosterone, predicts adverse outcomes, and decreases after adrenalectomy. Mechanistically, aldosterone enhances FAM20C-dependent phosphorylation/cleavage of iFGF-23, increasing cFGF-23 fragments. These data link mineral metabolism to aldosterone biology and suggest cFGF-23 as a prognostic biomarker.

Key Findings

• cFGF-23 levels were elevated in unilateral primary aldosteronism and showed a nonlinear increase with aldosterone, whereas iFGF-23 did not correlate with aldosterone.
• Higher preoperative cFGF-23 predicted adverse outcomes (mortality, cardiovascular/kidney events) and decreased after adrenalectomy.
• Aldosterone enhanced iFGF-23 cleavage via FAM20C in vitro; silencing FAM20C mitigated cFGF-23 fragment increase, while furin inhibition had no effect.

Clinical Implications

cFGF-23 measurement may aid prognostication and postoperative monitoring in primary aldosteronism, while highlighting FAM20C signaling as a potential therapeutic target alongside adrenalectomy.

Limitations

• Observational clinical associations without randomized intervention; sample size not specified in abstract
• In silico docking supports but does not prove direct aldosterone–FAM20C binding in vivo

Future Directions

Validate cFGF-23 as a prognostic biomarker in larger, multi-center cohorts; dissect in vivo FAM20C regulation by aldosterone and test pharmacologic modulation of the FAM20C–FGF-23 axis.