Endocrine Abstracts

JOINT2536

Introduction: Fibroblast Growth Factor 23 (FGF23) regulates phosphate homeostasis, but its systemic effects remain unclear in hypoparathyroidism. Elevated FGF23 levels have been linked to adverse renal, cardiovascular, and skeletal outcomes in patients without hypoparathyroidism. In chronic hypoparathyroidism, its role is not well defined, with limited evidence on its clinical implications.

Objective: To assess intact FGF23 levels in chronic hypoparathyroidism and their association with biochemical markers and clinical outcomes.

Methods: This observational study included 48 hypoparathyroid patients under regular follow-up at a university hospital. A cross-sectional analysis (2023–2024) evaluated clinical and biochemical parameters, complemented by a retrospective longitudinal analysis to identify predictors of FGF23 levels.

Results: The cohort (85. 4% women, 87. 5% postsurgical hypoparathyroidism, mean age 60. 6±16. 3years, disease duration 14. 8±12. 1years) was mostly on conventional therapy (44vs4 on teriparatide) and showed good biochemical control (mean serum calcium 8. 7±0. 8mg/dL, phosphate 4. 55±0. 82mg/dL, CaP product 39. 2±6. 8mg²/dL²). Despite this, 71% of patients had elevated FGF23 levels (157. 9±92. 4pg/mL; normal 23. 2–95. 4pg/mL), of whom only one patient on teriparatide. Higher FGF23 levels were associated with longer disease duration (19. 6±13. 1 vs 9. 6±8. 5years), reduced kidney function (49. 6±17. 3 vs 61. 5±16. 0mL/min/1. 73m²), higher CaP product (41. 3±7. 1 vs 37. 2±6. 0mg²/dL²), lower PTH (8. 7±8. 3 vs 14. 6±8pg/mL), and lower 1, 25OH vitamin D (30. 0±13. 0vs39. 8±13. 7pg/mL). However, treatments did not differ significantly in term of calcium doses (1801±1695mg/die vs 1359±1106mg/die) or calcitriol (0. 55±0. 46mg/die vs 0. 55±0. 33mg/die). Patients with higher CaP product had longer disease duration (19. 6±12. 8y vs 10. 0±9. 5 P = 0. 006), elevated FGF23 (187. 0±111. 2 vs 128. 9±57. 5pg/mL, P = 0. 028), and higher TmPO4/GFR (4. 4±0. 7vs3. 7±0. 7mg/dL, P = 0. 001). Lower tertiles of CaP product levels correlated weakly with TmPO4/GFR, suggesting significant FGF23 kidney resistance (R²=0. 082 and R²=0. 022), whereas this association was stronger in the highest tertile (R²=0. 268), suggesting a dose-dependent FGF-23 sensitivity. This mechanism, however, remains ineffective at inducing clinically-significant phosphate excretion. PTH level was associated with lower CaP product (34. 9±5. 6mg²/dl² vs 40. 2±5. 9mg²/dL² P = 0. 004), higher serum magnesium (2. 0±0. 2mg/dl vs 1. 9±0. 2mg/dl P = 0. 047) and lower calcium fractional excretion (1. 3±0. 5% vs 2. 2±1. 2% P = 0. 007). Multivariate analysis identified female sex (β=88. 76±41. 38, P = 0. 032) and mean CaP product (β=7. 99±2. 73, P = 0. 004) as independent predictors of FGF23 levels, independent of PTH, 1, 25OH vitaminD, renal function, serum magnesium and disease duration.

Conclusions: This study is the largest in literature investigating FGF23 levels in hypoparathyroidism. Despite adequate biochemical control, most patients exhibited elevated FGF23, driven by female sex and CaP product. High FGF23 levels were ineffective in promoting phosphate excretion but contributed to reduced 1, 25OH vitamin D, complicating conventional therapy management. FGF23 is clinically relevant in hypoparathyroidism and warrants further investigation.