Regulation of Fibroblast Growth Factor 23 (FGF23) by Thyroid Hormones in Levothyroxin-Induced Hyperthyroidism and the Role of Vitamin D3 in Bone Remodeling

Abstract

Background: Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that plays a crucial role in regulating phosphate homeostasis and vitamin D₃ metabolism. Thyroid hormones influence bone remodeling and mineral balance; however, the interaction between thyroid hormone imbalances and FGF23 remains incompletely understood.

Objective: This study aimed to investigate the effect of levothyroxine-induced hyperthyroidism on thyroid hormones (T3 and TSH) and serum FGF23 levels, as well as to evaluate the role of vitamin D₃ and calcium supplementation in mineral metabolism.

Methods: Thirty Wistar rats were divided into six groups (n = 5 each): a control group, a levothyroxine (50 μg/kg) treatment control group, a high-dose levothyroxine (200 μg/kg) group with calcium (400 mg/kg), a high-dose vitamin D₃ (1000 IU) group, and a high-dose vitamin D₃ (1000 IU) and vitamin K₂ (30 mg/kg) combination group. After one month, serum levels of T3, TSH, FGF23, calcium, phosphorus, and vitamin D₃ were measured using ELISA and spectroscopic methods.

Results: High doses of levothyroxine significantly increased T3 levels (3.103 ± 0.2035 ng/mL vs. 1.626 ± 0.0894 ng/mL, P < 0.001 in the control group) with a marked decrease in TSH levels (1.840 ± 0.2320 ng/mL vs. 3.864 ± 0.293 ng/mL in the control group, P = 0.036). Additionally, FGF23 levels were significantly elevated in the high-dose group (164.6 ± 7.273 pg/mL vs. 114.3 ± 9.450 pg/mL in the control group, P < 0.001). Vitamin D₃ and calcium supplementation also contributed to the reduction of FGF23 levels and improved mineral metabolism.

Conclusion: Levothyroxine-induced hyperthyroidism leads to elevated FGF23 levels, suggesting a regulatory axis between the thyroid gland and FGF23. Vitamin D₃ supplementation reduces this response and supports mineral balance, highlighting its potential as a preventative strategy for protecting bone health in hyperthyroidism.