TY - JOUR
T1 - Sorafenib-induced hypothyroidism is associated with increased type 3 deiodination
AU - Abdulrahman, Randa M.
AU - Verloop, Herman
AU - Hoftijzer, Hendrieke
AU - Verburg, Erik
AU - Hovens, Guido C.
AU - Corssmit, Eleonora P.
AU - Reiners, Christoph
AU - Gelderblom, Hans
AU - Pereira, Alberto M.
AU - Kapiteijn, Ellen
AU - Romijn, Johannes A.
AU - Visser, Theo J.
AU - Smit, Johannes W.
PY - 2010
Y1 - 2010
N2 - Therapy with tyrosine kinase inhibitors is associated with thyroid dysfunction. Decreased serum thyroid hormone levels during tyrosine kinase inhibitors are also observed in athyreotic patients with thyroid carcinoma. We therefore hypothesized that tyrosine kinase inhibitors may influence thyroid hormone metabolism. The aim was to study the effects of sorafenib therapy on serum thyroid hormone concentrations and iodothyronine deiodination in athyreotic patients. The design included a prospective open, single-center, single-arm 26-wk study. We measured serum thyroxine (T4), free T4, 3,5,3-triiodothyronine (T3), free T3, reverse T3 (rT3), and TSH concentrations at baseline and after 26 wk in 21 patients with progressive nonmedullary thyroid carcinoma treated with sorafenib. Ratios of T3/T4 and T3/rT3, which are independent of substrate availability and reflect iodothyronine deiodination, were calculated. Serum free T4 and T3 levels, adjusted for levothyroxine dose per kilogram body weight, decreased by 11 and 18%, respectively, whereas TSH levels increased. The serum T3/T4 and T3/rT3 ratios decreased by 18 and 22%, respectively, which is compatible with increased type 3 deiodination. Sorafenib enhances T4 and T3 metabolism, which is probably caused by increased type 3 deiodination
AB - Therapy with tyrosine kinase inhibitors is associated with thyroid dysfunction. Decreased serum thyroid hormone levels during tyrosine kinase inhibitors are also observed in athyreotic patients with thyroid carcinoma. We therefore hypothesized that tyrosine kinase inhibitors may influence thyroid hormone metabolism. The aim was to study the effects of sorafenib therapy on serum thyroid hormone concentrations and iodothyronine deiodination in athyreotic patients. The design included a prospective open, single-center, single-arm 26-wk study. We measured serum thyroxine (T4), free T4, 3,5,3-triiodothyronine (T3), free T3, reverse T3 (rT3), and TSH concentrations at baseline and after 26 wk in 21 patients with progressive nonmedullary thyroid carcinoma treated with sorafenib. Ratios of T3/T4 and T3/rT3, which are independent of substrate availability and reflect iodothyronine deiodination, were calculated. Serum free T4 and T3 levels, adjusted for levothyroxine dose per kilogram body weight, decreased by 11 and 18%, respectively, whereas TSH levels increased. The serum T3/T4 and T3/rT3 ratios decreased by 18 and 22%, respectively, which is compatible with increased type 3 deiodination. Sorafenib enhances T4 and T3 metabolism, which is probably caused by increased type 3 deiodination
U2 - https://doi.org/10.1210/jc.2009-2507
DO - https://doi.org/10.1210/jc.2009-2507
M3 - Article
C2 - 20484486
SN - 0021-972X
VL - 95
SP - 3758
EP - 3762
JO - Journal of clinical endocrinology and metabolism
JF - Journal of clinical endocrinology and metabolism
IS - 8
ER -