(1-34) Parathyroid hormone infusion acutely lowers fibroblast growth factor 23 concentrations in adult volunteers

Abstract

Background and objectives: Fibroblast growth factor 23 (FGF23) regulates phosphorus and vitamin D metabolism. Parathyroid hormone (PTH) infusion for 24 hours stimulated FGF23 secretion in healthy volunteers. The extent to which this was due to a direct stimulatory effect of PTH versus an indirect effect of increasing 1,25-dihydroxyvitamin D [1,25(OH)(2)D] levels was unclear.

Design, setting, participants, & measurements: Changes in FGF23 in 26 adults undergoing 6-hour (1-34) PTH infusion were examined, focusing particularly on the effects of PTH on FGF23 in the early period of infusion before sustained increases in 1,25(OH)(2)D.

Results: FGF23 levels declined in parallel with serum phosphate during infusion (P<0.05 for both), with both analytes decreasing within the first hour and reaching their respective nadirs at 6 hours. These changes were observed despite no change in 1,25(OH)(2)D levels during the first hour and a significant increase in 1,25(OH)(2)D from baseline after 6 hours (P<0.001). There were no differences in these responses by race. However, modest racial differences in the phosphaturic response to (1-34) PTH were observed (P=0.04 for interaction), with a higher rate of increase in fractional phosphate excretion in blacks than in whites.

Conclusions: During short-term (1-34) PTH infusion, FGF23 levels decreased in parallel with serum phosphate levels and despite significant increases in 1,25(OH)(2)D. When coupled with the results of prior longer-term infusion studies, these findings suggest that acute increases in PTH initially act to suppress FGF23 secretion, perhaps to mitigate urinary phosphate losses, before the stimulatory effect of 1,25(OH)(2)D on FGF23 eventually begins to predominate.

Figures

Figure 1.

Changes in blood biochemical variables in response to 6-hour (1-34) parathyroid hormone infusion. Serum phosphate (A), plasma fibroblast growth factor 23 (B), serum 1,25-dihydroxyvitamin D (C), serum total calcium (D), and plasma (1-84) parathyroid hormone concentrations (E) are presented. Results are reported as mean ± SEM. *P<0.05 (significant differences at individual time points compared with the within-group’s fasting level based on linear regression models).

Figure 2.

Changes in urine variables in response to 6-hour (1-34) parathyroid hormone infusion. Fractional excretion of phosphate (A) and fractional excretion of calcium (B) are presented. ▪, black participants; □, white participants. Results are reported as mean ± SEM. *P<0.05 (significant differences at individual time points compared with the within-group’s fasting level based on linear regression models).