Fibroblast growth factor (FGF)-23 in patients with primary hyperparathyroidism

Abstract

Objective: We aimed to determine the serum level of fibroblast growth factor-23 (FGF-23) in patients with primary hyperparathyroidism (pHPT) to understand its physiological role in the disorder. Patients and methods: Ninety-eight patients with pHPT who underwent parathyroidectomy formed the study group. We also measured serum FGF-23 in 11 of these patients on postoperative day 6. Results: Serum FGF-23 levels was significantly higher in pHPT patients than in healthy controls (35.6^17.8 ng/l vs 28.9^11.2 ng/l (mean^S.D.); P , 0.001 (Pearson's correlation coefficient)), but there was no significant difference in the serum FGF-23 level between pHPT patients with normal renal function (creatinine clearance (Ccr) of $70 ml/min) and healthy controls. Serum FGF-23 correlated positively with serum calcium (P , 0.0001) and intact parathyroid hormone (PTH) (P , 0.01), and negatively with Ccr (P , 0.001), serum phosphate (P , 0.05), and serum 1,25-dihydroxyvitamin D (1,25(OH) 2 D) (P , 0.05). Multiple linear regression analysis of factors potentially determining serum FGF-23 levels in pHPT patients showed serum calcium (P , 0.01) and Ccr (P , 0.001) to be significant predictors. The serum levels of FGF-23 did not change after parathyroidectomy despite the normalization of serum calcium values. Multiple linear regression analysis revealed that serum FGF-23 was not a significant predictor of serum phosphate or 1,25(OH) 2 D in pHPT patients. Conclusions: FGF-23 may not play a significant role in regulating phosphate or 1,25(OH) 2 D in pHPT patients, especially in those with normal renal function. Further studies are warranted to determine the role of FGF-23 in renal insufficiency or failure.European Journal of Endocrinology 151 55-60

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.…”

“…11 In contrast, no correlation between FGF-23 and serum phosphate levels was observed in nonuremic healthy humans, 8,27 and a inverse correlation was seen in patients with PHPT. 14,15 Even when alimentary intake of phosphorus is excessive, surplus phosphate is excreted very quickly by the kidneys, and hyperphosphatemia is not usually observed in healthy humans. In addition, hyperphosphaturia would be expected to occur in patients with PHPT secondary to elevated PTH levels.…”

“…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.…”

“…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. These mice develop not only abnormal parathyroid cell proliferation but also chronic biochemical hyperparathyroidism, with characteristic abnormalities in bone and, notably, a shift in the relationship between serum calcium and PTH.…”

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.…”