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Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-2498
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The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 7 4211-4215
Copyright © 2005 by The Endocrine Society

Fibroblast Growth Factor-23 in Patients with Graves’ Disease before and after Antithyroid Therapy: Its Important Role in Serum Phosphate Regulation

Hiroyuki Yamashita, Yuji Yamazaki, Hisashi Hasegawa, Takeyoshi Yamashita, Seiji Fukumoto, Takashi Shigematsu, Junichiro James Kazama, Masafumi Fukagawa and Shiro Noguchi

Noguchi Thyroid Clinic and Hospital Foundation (H.Y., S.N.), Oita 874-0932, Japan; Pharmaceutical Research Labs (Y.Y., H.H., T.Y.), KIRIN Brewery Co. Ltd., Takasaki 370-1295, Japan; Division of Nephrology and Endocrinology (S.F.), Department of Internal Medicine, Tokyo University Hospital, Tokyo 113-8655, Japan; Division of Nephrology (T.S.), Tokyo-Jikeikai Medical School Aoto Hospital, Katsushika 125-8506, Japan; Division of Clinical Nephrology and Rheumatology (J.J.K.), Niigata University Graduate School of Medicine and Dental Research, Niigata 951-8510, Japan; and Division of Nephrology and Dialysis Center (M.F.), Kobe University School of Medicine, Kobe 650-0017, Japan

Address all correspondence and requests for reprints to: Hiroyuki Yamashita, M.D., Ph.D., Noguchi Thyroid Clinic and Hospital Foundation, 6-33 Noguchi-Nakamachi, Beppu Oita 874-0932, Japan. E-mail: yama{at}noguchi-med.or.jp.

Objective: Hyperthyroidism is a well-described cause of hyperphosphatemia. We aimed to clarify the physiological role of fibroblast growth factor (FGF)-23 in serum phosphate homeostasis in patients with Graves’ disease during the course of treatment for hyperthyroidism.

Context: The study group comprised 56 patients (45 for a cross-sectional study and 11 for a longitudinal study) with Graves’ disease. For the cross-sectional study, patients were assigned, on the basis of their serum phosphate level, to a hypophosphatemia group (n = 14), a normophosphatemia group (n = 16), or a hyperphosphatemia group (n = 15). Serum FGF-23, calcium, phosphate, PTH, and 1,25-dihydroxyvitamin D [1,25(OH)2D] levels were compared between the three groups. For the longitudinal study, we assessed changes in these biochemical indices before and after antithyroid treatment.

Results: In the cross-sectional study, the serum FGF-23 level was significantly higher (P < 0.05) in the hyperphosphatemia group than in the other groups (61 ± 36 ng/liter vs. 31 ± 22 ng/liter and 30 ± 9 ng/liter). In the longitudinal study, serum levels of FGF-23 decreased significantly (P < 0.05) from a high of 54 ± 12 ng/liter before treatment to 29 ± 14 ng/liter after treatment. In contrast, the serum 1,25(OH)2D level increased significantly (P < 0.005) from 55 ± 22 pmol/liter before treatment to 185 ± 76 pmol/liter 3 months after treatment. Serum FGF-23 levels were positively correlated with serum phosphate levels (P < 0.0001) and negatively correlated with serum 1,25(OH)2D levels (P < 0.0001).

Conclusions: The significant positive correlation between serum levels of phosphate and FGF-23 indicates that FGF-23 may play an important role in serum phosphate homeostasis by its up-regulation in the hyperphosphatemic condition.







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