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

Matteo Malagrinò; Anna Piazza; Nicolò Bisceglia; Sara Capra; Cristiana Cantone; Uberto Pagotto; Guido Zavatta

doi:10.1210/jendso/bvaf217

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

J Endocr Soc. 2025 Dec 20;10(2):bvaf217. doi: 10.1210/jendso/bvaf217. eCollection 2026 Feb.

Authors

Matteo Malagrinò^{1

2}, Anna Piazza^{1

2}, Nicolò Bisceglia^{1

2}, Sara Capra^{1

2}, Cristiana Cantone^{1

2}, Uberto Pagotto^{1

2}, Guido Zavatta^{1

2}

Affiliations

¹ Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy.
² Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna 40138, Italy.

Abstract

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 × 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 × P product 39.2 ± 6.8 mg²/dL²). 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 × P product (P = .036). Despite elevated FGF23, TmPO₄/GFR was paradoxically increased, suggesting impaired renal responsiveness. Female sex and Ca × 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.

Keywords: FGF23; calcium-phosphate product; hypoparathyroidism; kidney; management; phosphate.