Fibroblast Growth Factor-23 (FGF23) in Patients with Transient Hypoparathyroidism: Its Important Role in Serum Phosphate Regulation

Abstract

Abstract. Hypoparathyroidism is a complication of thyroidectomy that causes hyperphosphatemia primarily due to enhanced reabsorption of phosphate in the kidney resulting from decreased parathyroid hormone (PTH) secretion. Fibroblast growth factor-23 (FGF23) is a hormone-like factor that is thought to play an important role in phosphate homeostasis. However, the changes and role of FGF23 in transient hypoparathyroidism after thyroidectomy are not clear. We examined changes in serum levels of calcium, phosphate, intact PTH, 1,25-dihydroxyvitamin D, and FGF23 in 12 patients (10 women, 2 men; mean age, 51 yr) who developed transient hypoparathyroidism after thyroidectomy. Serum phosphate reached its peak level (5.9 ± 0.5 mg/dl) approximately 4 days after development of hypoparathyroidism, and this was followed by a peak in the serum FGF23 level (71 ± 28 ng/l). Serum levels of calcium, phosphate, and FGF23 normalized after recovery of parathyroid function. There was a significant positive correlation between serum phosphate and FGF23 levels (P<0.05). Serum FGF23 was elevated in patients with hypoparathyroidism and hyperphosphatemia and normalized along with normalized phosphate levels after recovery of parathyroid function. The peak level of phosphate always preceded that of FGF23 by several days, suggesting that elevated phosphate is a primary stimulus for release of FGF23. This homeostatic regulation of phosphate differs considerably from that of serum calcium whose change is rapidly corrected within minutes.Key words: Fibroblast growth factor-23, Hypoparathyroidism, Hyperphosphatemia (Endocrine Journal 54: 465-470, 2007) PARATHYROID hormone (PTH) and the vitamin D-endocrine system play key roles in the regulation of serum phosphate levels through their actions on the kidney and intestine. However, PTH and 1,25-

Generation of mice encoding a conditional null allele of Gcm2

“…These observations are consistent with emerging evidence for a complex regulatory mechanism for FGF23 secretion that involves PTH (Silver and Naveh-Many 2012) as well as serum concentrations of calcium and phosphorus to ensure a normal calcium × phosphorus product (Quinn et al 2013). By contrast, previous studies of patients with chronic (Gupta et al 2004) or acute and transient hypoparathyroidism (Yamashita et al 2007) had shown that levels of serum FGF23 were increased, and were correlated with hyperphosphatemia. But in these cases the patients were also receiving calcitriol or 1α-hydroxyvitamin D, which would increase FGF23 (Collins et al 2005; Gupta et al 2004).…”

Oral calcium supplementation reverses the biochemical pattern of parathyroid hormone resistance in underprivileged Indian toddlers

“…The median serum PTH level was 6.0 pmol/l (4.00–9.00) and 25 out of 51 (49%) toddlers had PTH above the upper end of the reference range value of 6.4 pmol/l. At the start of the trial in September 2006, the mean (SD) serum 25(OH)D concentration for the whole group was 126.3 (SD 62.6) nmol/l, indicating that the subjects had good body stores of vitamin D. For the whole group, the median FGF-23 level was 9.1 ng/l (5–14.2), which is just below the adult reference range of 10–50 nmol/l 19. Serum FGF-23 concentration was not related to serum phosphorus concentration.…”

The Journey From Vitamin D–Resistant Rickets to the Regulation of Renal Phosphate Transport

“…Dietary/serum calcium regulates FGF23 production (Figure 3), whereas serum calcium may alter renal phosphate excretion (74). Although FGF23 levels rise after transient hypoparathyroidism, the level achieved is insufficient to correct the serum phosphorus (75). This "inadequate" FGF23 response may be protective because a more robust rise in FGF23 could further suppress 1,25(OH)D and PTH production, Figure 4.…”