FT3 and FT3/FT4 ratio are decreased and not compensated by levothyroxine treatment in TKI-treated thyroid cancer patients

Tyrosine kinase inhibitors (TKIs) can alter thyroid hormone levels in multiple cancer contexts. The aim of this study was to analyse the efficacy of levothyroxine (LT4) treatment to normalise thyroid hormone levels in thyroid cancer patients with increased thyroid-stimulating hormone (TSH) after TKI initiation. Forty-five consecutive patients were enrolled. One month after TKI initiation, TSH increased from 0.21 (IQR: 0.07-0.8) to 1.09 mIU/L (IQR: 0.16-4.1) (P < 0.0001), and the FT3/FT4 ratio decreased from 2.1 (IQR: 1.86-2.66) to 1.92 (IQR 1.69-2.3) (P < 0.001) compared to baseline. During the first year of TKI treatment, in 23 patients (51%), TSH increased >4 mIU/L with a concomitant decrease in both FT3 and FT4. An increase in the LT4 daily dose of 0.62 ± 0.44 μg/kg normalised TSH to baseline levels in all patients, but in 11 patients FT3 remained lower compared to baseline, i.e. 2.53 (IQR: 2.4-2.75) versus 3.5 pg/mL (IQR: 3.18-3.84), respectively (P = 0.001). Following this observation, in three consecutive patients with increased TSH and reduced FT3 during TKI treatment, we changed the LT4 monotherapy into an LT4 + LT3 combination at a ratio of 11:1. Two months later, serum TSH, FT3 and FT4 were all similar to baseline (P > 0.05 in all determinations). In conclusion, TKI-related increase in TSH was associated with decreased FT3 and FT3/FT4 ratio. This was not compensated by an increase in LT4 in half of the cases. The clinical impact of compensating for the low T3 levels in these patients should be addressed in prospective trials.