toceranib-phosphate and Hypothyroidism

Tyrosine kinase inhibitors are widely utilized in veterinary oncology for the treatment of mast cell and solid tumours. In man, these drugs are associated with thyroid dysfunction: however, to date only one study has investigated this in dogs. The aim of this study was to prospectively assess thyroid function in a group of dogs with cancer receiving toceranib. Thirty-four dogs were prospectively enrolled at two referral hospitals into two groups; those receiving toceranib with prednisolone and those receiving toceranib alone. Total thyroxine (TT4) and thyroid stimulating hormone (TSH) was monitored at regular time points during treatment. Follow-up data was available for 19 dogs. Overall, 12 incidences of elevated TSH occurred but none of these dogs had concurrent low TT4 concentrations. There was a significant difference in median TSH at week six compared with baseline. Hypothyroidism was not diagnosed in any patient during the study period. Patient drop-out was higher than anticipated which prevented the assessment of longer term toceranib administration on thyroid function. Toceranib therapy was not associated with hypothyroidism in this study but did result in elevations in TSH which confirms what has been previously reported. Toceranib should be considered to cause thyroid dysfunction in dogs and monitoring is advised.

Topics: Animals; Dog Diseases; Dogs; Female; Hypothyroidism; Indoles; Male; Neoplasms; Prospective Studies; Pyrroles; Thyroid Gland; Thyrotropin; Thyroxine; United Kingdom

Thyroid dysfunction is associated with the use of tyrosine kinase inhibitors (TKI) in people.. To determine whether dysfunction in the hypothalamic-pituitary-thyroid axis occurs in dogs receiving the TKI, toceranib phosphate.. Forty-three client-owned dogs with cancer.. Prospective, observational study. Concentrations of total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), and thyroid-stimulating hormone (TSH) were evaluated on day 0, 30, and 90. Dogs also were evaluated for the presence of thyroglobulin autoantibodies.. The proportion of dogs with low TT4, low FT4, low TT3, high TSH, or primary hypothyroidism (increased TSH and decreased TT4, FT4 or both) did not change over 90 days. Hormone concentrations remained within laboratory reference intervals, but FT4 (P = 0.0032) and TSH (P < 0.0001) changed over time. Mean FT4 was 1.22 ng/dL (95% confidence interval [CI], 1.10-1.34) on day 0 and 1.00 ng/dL (95% CI, 0.86-1.16) on day 90. Mean TSH was 0.17 ng/mL (95% CI, 0.13-0.23) on day 0 and 0.34 ng/mL (95% CI, 0.24-0.48) on day 90. Furthermore, TT4/TT3 ratio also changed over time (P = 0.0086). Mean TT4/TT3 ratio was 2.57 (95% CI, 2.26-2.88) on day 0 and 2.02 on day 90 (95% CI, 1.61-2.44). Thyroglobulin autoantibodies were not detected in any dog.. Toceranib phosphate can disrupt the hypothalamic-pituitary-thyroid axis in dogs. Periodic evaluation of TT4, FT4, TT3, and TSH should be carried out in dogs receiving long-term treatment with this medication.

Topics: Animals; Autoantibodies; Dog Diseases; Dogs; Female; Hypothalamus; Hypothyroidism; Indoles; Male; Neoplasms; Pituitary Gland; Prospective Studies; Pyrroles; Thyroglobulin; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine