Elevated FGF23 Despite Biochemical Control Reveals Hidden Mineral Dysregulation in Chronic Hypoparathyroidism

Background Fibroblast growth factor (FGF23) is a phosphate-regulating hormone and might be a biomarker of cardiorenal comorbidities in the general population. Its role in hypoparathyroidism is unclear.Objective To assess the prevalence of abnormal FGF23 concentrations in patients with chronic hypoparathyroidism and explore their associations with mineral metabolism and renal phosphate handling.Design Cross-sectional, observational study complemented by a retrospective longitudinal analysis of biochemical parameters over a median follow-up of 5 years.Patients Forty-eight consecutive patients with chronic hypoparathyroidism (mean age 60.6 +/- 16.3 years; 85% women; 87.5% postsurgical) evaluated at an academic medical center between January 2023 and December 2024.Measurements Serum intact FGF23 levels, serum calcium (Ca) and phosphate (P), Ca x P product, PTH, 1,25-dihydroxyvitamin D [1,25(OH)2D], estimated glomerular filtration rate (eGFR), and renal phosphate reabsorption [maximum rate of renal tubular reabsorption of phosphate/glomerular filtration rate (TmPO4/GFR)].Results Elevated FGF23 levels were found in 71% of patients (mean 157.9 +/- 92.4 pg/mL; reference range 23.2-95.4), despite adequate biochemical control (calcium 8.7 +/- 0.8 mg/dL; phosphate 4.5 +/- 0.8 mg/dL; Ca x P product 39.2 +/- 6.8 mg(2)/dL(2)). FGF23 was associated with longer disease duration (P = .004), lower eGFR (P = .008), lower PTH (P = .03), reduced 1,25(OH)2D (P = .016), and elevated Ca x P product (P = .036). Despite elevated FGF23, TmPO4/GFR was paradoxically increased, suggesting impaired renal responsiveness. Female sex and Ca x P product were independent predictors of FGF23 levels.Conclusion FGF23 is frequently elevated in chronic hypoparathyroidism, indicating a disrupted phosphate metabolism, and its increase seems to be ineffective in promoting phosphate excretion, probably due to renal resistance mechanisms. Further studies are needed to clarify the role of FGF23 as a clinical biomarker, risk factor, and potential therapeutic target in this population.