INTRODUCTION: Primary hyperparathyroidism (PHPT) often causes hypercalcemia and complications requiring parathyroidectomy (PTX). Anemia affects 15-50% of PHPT patients, but its mechanisms remain unclear. While parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) contribute to anemia in secondary hyperparathyroidism (SHPT) through erythropoietin (EPO) resistance and bone marrow fibrosis, their roles in PHPT are less defined.This study explores the effect of PHPT on erythropoiesis by assessing hemoglobin, EPO, and FGF23 levels before and after PTX. METHODS: In a monocentric longitudinal study (2018-2020), PHPT patients scheduled for PTX were followed for six months. Blood and urine samples were collected at baseline (surgery day), at ten days and six months post-surgery. Pearson correlation assessed relationships between hemoglobin, EPO, PTH, FGF23, calcium, and phosphate at baseline and six months. Mixed-effects models evaluated the impact of PTH and FGF23 on hemoglobin, adjusting for confounders. RESULTS: In a cohort of 111 PHPT patients (81% women, median age 64, normal BMI), anemia prevalence decreased from 9.9% at baseline to 2.7% six months post-PTX, despite stable EPO levels. Post-surgery, PTH, FGF23, and calcium significantly decreased. PTH did not significantly correlate with hemoglobin or EPO at any timepoint. Before surgery, FGF23 negatively correlated with hemoglobin (R=-0.20, p=0.020) and positively correlated with log-EPO (R=0.38, p<
0.001). Mixed-effects models showed no predictive effect of PTH on hemoglobin. However, multivariable models indicated a significant association between FGF23 and declining hemoglobin (β=-0.01, 95%CI [-0.02
-0.01]). CONCLUSION: Anemia in PHPT is linked to elevated FGF23 levels, potentially causing EPO resistance.