Regulation of plasma fibroblast growth factor 23 by calcium in primary hyperparathyroidism

Abstract

Objective: While the importance of fibroblast growth factor (FGF)-23 is established in phosphate-wasting disorders, little is known about the mechanisms regulating its circulating level. To investigate the role of parathyroid hormone (PTH) and calcium in FGF-23 metabolism, we examined plasma FGF-23 levels in patients with primary hyperparathyroidism (PHPT). Patients and methods: Fifty patients with PHPT and 52 controls were employed in this study. Plasma was obtained from 18 PHPT patients who underwent parathyroidectomy (PTX) on the first postoperative morning without vitamin D administration. Time-course samples were also obtained from 5 of 18 PTX patients without vitamin D analogs or calcium administration. The expression of Fgf23 on resected parathyroid glands was analyzed by reverse transcription (RT) -PCR and immunohistochemistry. Results: FGF-23 was significantly elevated in PHPT patients compared with controls. FGF-23 levels were significantly correlated positively with serum corrected calcium and intact PTH levels, and negatively with creatinine clearance and inorganic phosphate, among which creatinine clearance and corrected calcium were independently associated factors. In 18 PTX patients, postoperative FGF-23 levels were significantly decreased compared with preoperative levels. Corrected-calcium levels were significantly decreased 1 h after PTX, and this was followed by a reduction in plasma FGF-23 levels in time-course study. In addition, postoperative FGF-23 levels in 18 PTX patients were significantly correlated with corrected calcium, consistent with a role of serum calcium as one of the major regulators of FGF-23. The absence of Fgf23 expression in parathyroid glands indicated that the parathyroid glands were not major sources of circulating FGF-23. Conclusions: Serum calcium may regulate circulating FGF-23 levels in PHPT.European Journal of Endocrinology 154 93-99

Parathyroid Hormone Regulates Fibroblast Growth Factor-23 in a Mouse Model of Primary Hyperparathyroidism

“…16 In these mice, serum FGF-23 levels were more strongly correlated with serum calcium levels than with PTH levels. The same trend was also reported in patients who had PHPT with 14 and without 15 renal insufficiency. Because PTH mobilizes calcium from the bone to the circulation, the direct correlation of FGF-23 with calcium would likely be a result of PTH activity.…”

“…After PTX, FGF-23 levels in PC2 mice significantly decreased to the levels of age-matched WT mice, indicating that PTH is a potential stimulator of serum FGF-23 levels in vivo in PHPT. In clinical studies of PHPT, circulating FGF-23 levels decreased significantly after PTX in patients with normal kidney function 15 and decreased-but not significantly-in patients with renal insufficiency. 14 Administration of vitamin D analogs 9,19 and/or calcium, 15 as well as renal insufficiency, 20 may interfere with the decrement of circulating FGF-23 levels after PTX.…”

“…FGF-23 concentrations are significantly directly correlated with serum calcium and intact PTH levels and inversely correlated with creatinine clearance and phosphate concentration; of these, creatinine clearance and calcium are independently associated factors. 14,15 Although both of these clinical studies suggested the importance of PTH action in the regulation of FGF-23 in patients with PHPT, serum FGF-23 levels decreased significantly after parathyroidectomy (PTX) in one study, 15 whereas the decrease was NS in the other. 14 Here we used PTH-cyclin D1 transgenic (PC2) mice, which exhibit parathyroid-targeted overexpression of the human cyclin D1 oncogene, as a model of PHPT.…”

FGF-23: estado da arte

“…66 Another unanswered question is the role of Ca in FGF-23 regulation, in addition to the other two known regulators of that hormone (P and calcitriol). A study conducted with patients with primary hyperparathyroidism and undergoing parathyroidectomy has revealed that serum FGF-23 levels correlated with serum Ca levels, regardless of serum P. 67 Another study with mice without vitamin D receptors has shown that calcium can be another determinant for the production of FGF-23. In those animals, FGF-23 levels were almost undetectable.…”

Phosphatemic Effect of Cinacalcet in Kidney Transplant Recipients With Persistent Hyperparathyroidism

“…1,2 The recently described bone hormone fibroblast growth factor 23 (FGF-23) decreases phosphorus reabsorption through changes in the type 2a sodium-phosphate transporter and suppresses 1␣-hydroxylase activity in the kidney. 3,4 Circulating FGF-23 levels are increased in patients with primary, 5,6 secondary, [7][8][9] and persistent hyperparathyroidism 10,11 and contribute to the development of early posttransplantation hypophosphatemia. 12 Calcimimetics decrease PTH production and secretion by increasing the sensitivity of the calcium-sensing receptor to calcium on chief cells of the parathyroid gland.…”