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

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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