Suppression of circulating fibroblast growth factor-23 by cinacalcet in patients with primary hyperparathyroidism
Yasuo Imanishi, Masafumi Kurajoh, Keisuke Kobayashi, Akira Ishii, Tomoki Nagata, Takami Miki, Masaaki Inaba & Yoshiki Nishizawa
While the importance of fibroblast growth factor 23 (FGF-23) is established in the pathogenesis of phosphate wasting disorders, little is known about the mechanisms regulating its circulating level. To investigate the role of parathyroid hormone (PTH) in FGF-23 homeostasis, cinacalcet hydrochloride, a calcimimetic compound to suppress PTH secretion, was administered to the patients with primary hyperparathyroidism (PHPT). Fourteen patients with PHPT, who met the guidelines of the National Institutes of Health for parathyroidectomy, were enrolled in this study with written informed consent. Thirty milligrams cinacalcet was administered twice daily, 12 h apart. Fasting serum was obtained before administration of cinacalcet on designated days. For further examinations, serum was obtained at 0, 2 and 4 h after administration on day 1 and 3. Fasting serum examinations revealed that corrected Ca decreased significantly from 3 days after administration, P increased from 3 days, FGF-23 decreased from 8 days, however, no significant changes were observed in serum whole PTH and 1,25(OH)2D, compared to pre-administrations. On day 1, FGF-23 and whole PTH decreased significantly at 2 and 4 h after administration, however, no significant changes were observed in corrected Ca, P and 1,25(OH)2D. Similar results were obtained at day 3. Significant but transient suppression of PTH at 2 and 4 h after cinacalcet administration enabled to distinguish the role of PTH and Ca on FGF-23 regulation. PTH is suggested to elevate circulating FGF-23, in part not via Ca increment, in PHPT.