PSAT173 Weekly Supplementation with Vitamin D3 reduces 1,25(OH)2 vitamin D3 Measured by Mass Spectrometry, and increases Fibroblast-like growth factor 23 (FGF23) in Individuals with and without Primary Hyperparathyroidism (PHPT)

INTRODUCTION: Vitamin D deficiency is a very common condition, which has been associated with more severe presentations of PHPT. It has been suggested that the Vitamin D replacement improves this prognosis, but there are few data regarding its effect on mineral homeostasis. The aim of this research was to evaluate the effects of weekly Vitamin D supplementation on the mineral metabolism in this population.Material and methods: In this prospective case-control trial, we evaluated the effects of 14,000 IU/week of oral Vitamin D(3), for 12 weeks, on albumin-adjusted total Calcium (TCa), Parathormone (PTH), 25 hydroxyvitamin D(3) (25OHD), intact FGF23 and 1,25dihydroxyvitamin D(3) (1,25(OH)2D), in addition to other biochemical markers. Volunteers with active PHPT (n=55) and paired controls (n=64) collected fasting blood samples before and after 12 weeks of the Vitamin D supplementation. 1,25(OH)2D was measured by liquid chromatography and mass spectrometry, and other hormones by commercial immunometric assays. P<0.05 was considered significant. RESULTS: At baseline there were no differences between groups regarding 25OHD, FGF23 and clearance of creatinine. As expected, the concentrations of TCa, PTH, 1,25(OH)2D were higher in the PHPT. After supplementation, TCa and PTH did not change despite the significant increase on 25OHD in both groups, more markedly in the controls (from 22.7±6.1 to 31.5±6.8 ng/mL in PHPT; and from 20.4±5.8 to 32.5±6.4 ng/mL in controls). FGF23 levels significantly increased after supplementation in both groups, more markedly in the PHPT. (from 47.9 ± 27.1 to 76.3 ± 33.3 pg/mL in PHPT and from 40.5 ± 13.9 to 59.8±19.8 pg/mL in controls). A significant reduction in the concentrations of 1,25(OH)2D was seen in both groups, (time effect p-value<0.001), with more intensity in the PHPT group (time x group effect p-value=0.015) (from 94.8±34.6 to 68.9±25.3 pg/mL in PHPT and from 68.7±23.5 to 56.4±20.7pg/mL in controls). The delta of 1,25(OH)2D was inversely correlated with the delta of FGF23 in both the PHPT (r=-0.302, p-value=0.028) and control (r=-0.278, p-value=0.027) groups. CONCLUSION: In both patient groups (with and without PHPT), weekly administration of 14,000IU of Vitamin D3 reduced 1,25(OH)2D concentrations measured by mass spectrometry, probably due to the inhibition of 1α-hydroxylase induced by the increase in FGF23. This phenomenon could explain the absence of hypercalcemia after supplementation, even in individuals with active PHPT, appearing to be a protective mechanism against Vitamin D excess. Future studies are needed to see if this increase in FGF23 could explain the paradoxical effects observed with the high bolus doses of vitamin D described by others.*This research received public grants from FAPESP (Fundação de Amparo a Pesquisa do Estado de Sao Paulo), with technical support from Laboratorio Fleury Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.