Changes in Plasma Fibroblast Growth Factor-23 (Fgf-23) Concentrations after Treatment of Hyperthyroidism (Hth) in Cats with Variable Renal Function

Williams T.L., Elliott J. and Syme H.M.

Conference Proceedings, (2011). American College of Veterinary Internal Medicine:


FGF-23 is secreted by osteocytes and osteoblasts in response to hyperphosphatemia. FGF-23 enhances phosphaturia and is postu- lated to have a central role in the development of secondary renal hyperparathyroidism. Hyperthyroid cats have elevated plasma phosphate and parathyroid hormone concentrations, which may in part be associated with underlying chronic kidney disease (CKD). The aim of this study was to determine if plasma FGF-23 concentra- tions were associated with the presence of underlying CKD in hyperthyroid cats, and to investigate the changes in plasma FGF– 23 concentrations that occur following treatment of HTH.

Hyperthyroid cats were recruited from two London-based first opinion practices between 1999 and 2009. Cats that were azotemic at diagnosis were excluded. HTH was treated with anti-thyroid medica- tion alone or in combination with thyroidectomy. Cats were included in the study if they had a plasma total thyroxine concentra- tion o 40nmol/l documented for a six month period following commencement of treatment. Cats were classified as having azotemic CKD if they developed renal azotemia within six months of establishment of euthyroidism. Otherwise cats were deemed to have normal renal function. Stored EDTA plasma samples were assayed for FGF-23 using a recently validated ELISA. The Mann-Whitney U test and the Wilcoxon signed rank test were used to compare

between the groups and assess the response to treatment respectively. Results are reported as median [25th, 75th percentiles]. Correlations were made using Spearman’s correlation coefficient.

Thirty one cats with HTH (14 azotemic and 17 non-azotemic) were included in the study. Plasma phosphate concentrations decreased following treatment in cats that did not develop azotemia (4.84 [3.91, 5.64]mg/dl vs. 3.91 [3.38, 4.37] mg/dl; n 5 13, P 5 0.01) whereas plasma phosphate concentrations did not change significantly follow- ing treatment in cats that did develop azotemia (4.28 [3.81, 5.64] mg/ dl vs. 4.22 [3.10, 5.33] mg/dl; n 5 14, P 5 0.158). Plasma FGF–23 concentrations were significantly higher in cats that developed azotemia than cats that did not at both pre treatment (211.7 [176.4, 356.3] pg/ml vs. 148.3 [118.8, 274.9] pg/ml; P 5 0.039) and post treatment (514.0 [250.2, 800.0] pg/ml vs. 195.1 [160.7, 287.3] pg/ml; P 5 0.001) timepoints. Plasma FGF-23 concentrations increased following treatment in both azotemic (P 5 0.004) and non-azotemic groups (P 5 0.025). Plasma FGF-23 concentrations and plasma phosphate concentrations were not correlated at baseline (rs 5 0.189, P 5 0.335) or following treatment (rs 5 0.136, P 5 0.472).

Plasma FGF-23 concentrations were higher in pre-azotemic cats than non-azotemic cats and increased following treatment of HTH. The reason that FGF-23 concentrations increased following treat- ment, particularly in the face of decreasing plasma phosphate concentrations in cats that remain non-azotemic, is unclear but may be related to the decline in glomerular filtration rate.