Endocrine Abstracts

Background: Recent studies suggest enhanced peripheral thyroid hormone metabolism as an explanation for the changes in thyroid hormone levels in patient treated with Sorafenib.

Methods: In this single centre, prospective, observational cohort study 60 patients with hepatocellular carcinoma were treated with Sorafenib. Thyroid stimulating hormone (TSH) and free thyroxine (FT4) were measured at baseline (time-0), at 6 weeks (time-1) and at the end of therapy (time-end).

In 36 patients extensive thyroid hormone profile including thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) was determined.

Results: Four patients (7%) developed clinically significant thyroid disorder compatible with thyroiditis. Interestingly, nineteen patients (33%) showed mild thyroid disturbances with increasing FT4 or TSH. The mean FT4 increased significantly from time-0 to time-1 from 18.7 to 21.0 pmol/l, P<0.001. TSH levels increased from 1.78 to 2.54 mU/l, P<0.001.

T3 concentrations decreased significantly, whereas rT3 and T4 increased significantly. The serum T3/rT3 ratio significantly decreased from 3.91 to 3.85 (P<0.001) and the rT3/T4x100 ratio significantly increased from 0.41 to 0.48 (P<0.001).

From time-1 to time-end FT4 increased further from 21.0 to 22.4 pmol/l (P<0.01). TSH, T3/rT3 ratio and rT3/T4x100 ratio did not show significant changes from time-1 to time-end.

Conclusions: Thyroiditis occurred in 7% of the patients. The increase in FT4 in combination with an increased TSH suggests an altered setpoint of the hypothalamus pituitary thyroid-axis. The marked decrease in the T3/rT3 ratio and increase in the rT3/T4 ratio in patients during the treatment with Sorafenib, suggests increased type D3 deiodination and diminished D1 activity.