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Sorafenib alters thyroid hormone levels in patients with hepatocellular carcinoma

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June 16, 2017

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Sorafenib appeared to alter thyroid function in patients undergoing treatment for hepatocellular carcinoma by inhibiting triiodothyronine transportation, according to researchers in the Netherlands.

“A study in athyroid patients treated with sorafenib suggests that there may be an enhanced peripheral degredation of thyroid hormone by deiodinase type 3,” Carolien M. Beukhof, MD, of the department of internal medicine at Rotterdam Thyroid Center, and colleagues wrote. “Inhibition of [thyroid hormone] uptake via the cellular [thyroid hormone transporter] monocarboxylate transporter 8 has been shown for sunitinib, imatinib, dasatinib and bosutinib, but for sorafenib this has not been studied.”

Beukhof and colleagues performed a prospective cohort study of 57 patients with hepatocellular carcinoma who received sorafenib between 2009 and 2016. The researchers measured patients’ free T4 and thyroid-stimulating hormone (TSH) levels every 6 weeks. When enough serum was available, the researchers performed extensive thyroid function tests at baseline, 6 weeks and after therapy was completed. Beukhof and colleagues also tested the effect of sorafenib on monocarboxylate transporter 8 and monocarboxylate transporter 10, performing in vitro experiments on transfected COS1 cells.

Seven percent (n = 4) of patients developed thyroiditis, Beukhof and colleagues reported. Nearly one-third (30%) showed free T4 or TSH levels above the normal range. At 6 weeks, overall mean TSH levels increased from 1.28 to 1.57 mU/L (P < .001), while mean free T4 levels rose from 18.4 to 21.2 pmol/L (P < .001). The serum T3/rT3 ratio significantly decreased by 6 weeks, falling from 4.84 to 3.68 (P < .001). The T3/T4 x100 ratio also decreased, falling from 1.88 to 1.58 (P = .002), the researchers wrote.

Median progression-free survival among patients with thyroiditis was 16.3 months (95% CI, 6.1-26.5), compared with 4.9 months in those without thyroiditis (95% CI, 2.3-7.5), whereas median overall survival was 18.5 months (95% CI, 0.1-43.5) for those with thyroiditis and 10.8 months (95% CI, 8.6-13) in those without.

Beukhof and colleagues wrote that sorafenib “significantly decreased cellular T3 uptake by [monocarboxylate transporter 8] and to a lesser extent by [monocarboxylate transporter 10].

Tyrosine kinase inhibitors have important role in the treatment of cancer and are reported to be associated with changes in thyroid function. Our data in patients with hepatocellular carcinoma suggest that sorafenib affects thyroid function tests on multiple levels,” Beukhof told Endocrine Today. “Our experiments show a possible role of sorafenib-induced inhibition of thyroid hormone transport into the cell by thyroid hormone transporters. – by Andy Polhamus

Disclosure: The researchers report no relevant financial disclosures.

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