Phosphate metabolism in primary hyperparathyroidism: a real-life long-term study

Purpose: Parathyroid hormone controls calcium and phosphate metabolism. The latter is also regulated by both FGF23 and 1-25(OH)2VitaminD. The polymorphic variant c.716 C > T of the FGF23 gene was previously found to be associated with renal phosphate leak/nephrolithiasis. The aim of our research is to study the metabolism of phosphate in a cohort of patients with primary hyperparathyroidism (PHPT) and its impact on bone and kidney. Methods: We have retrospectively compared a large sample of sporadic PHPT patients (339) with historical comparison cohort (HCC 503: Olivetti Study Group and Siena Osteoporosis Study). Moreover, in 51 PHPT patients, phosphate metabolism indexes were also revaluated at least 2 years after surgical cure. The variant c.716 C > T of the FGF23 gene was genotyped in patients and in a small sample of the control group. Results: In PHPT patients we found higher levels of serum calcium, PTH, alkaline phosphatase, beta-C-terminal telopeptide (CTx), urinary calcium, while serum phosphate, 25OH-VitaminD, maximal tubular renal phosphate reabsorption adjusted for glomerular filtration rate (TmPO4/GFR) were lower than what was found in HCC. In PHPT patients fibroblast growth factor 23 (FGF23) levels were higher than in controls. Patients with kidney stones carried the 716 T allele more frequently than patients without it (χ2 7.20, p = 0.027). In PHPT patients revaluated at least 2 years after surgery, we observed a significant reduction of 1-25(OH)2VitaminD and FGF23. According to the median of serum phosphate levels, PHPT patients were subdivided into two subgroups: ≤2.8 mg/dL and > 2.8 mg/dL. The lowest phosphate group had a significantly higher serum calcium, PTH, 1-25(OH)2VitaminD, urinary calcium and a higher prevalence of kidney stones than in the highest phosphate group. The rate of males in the lowest phosphate group was significantly higher than in the highest phosphate group. Conclusion: Our study shows that the regulators of phosphate metabolism in PHPT patients are higher than controls and they significantly reduce after surgical cure. PHPT patients with low serum phosphate have a worse biochemical and clinical phenotype.