Sorafenib-induced changes in thyroid hormone levels in patients treated for hepatocellular carcinoma.

Sorafenib-induced changes in thyroid hormone levels in patients treated for hepatocellular carcinoma.

J Clin Endocrinol Metab. 2017 May 26;:

Authors: Beukhof CM, van Doorn L, Visser TJ, Bins S, Visser WE, van Heerebeek R, van Kemenade FJ, de Rijke YB, de Herder WW, Chaker L, Mathijssen RH, Peeters RP

Abstract
Context: The pathogenesis of tyrosine kinase inhibitor-induced thyroid hormone (TH) alterations and the effects on TH metabolism and transport are still a matter of debate.
Objective: To study the effects of sorafenib on TH levels in patients with hepatocellular carcinoma (HCC) and evaluate possible mechanisms underlying these changes.
Design: Prospective cohort study between 2009 and 2016.
Setting: Tertiary referral center.
Patients: 57 Consecutive patients with HCC who were treated with sorafenib.
Main Outcome Measure: TSH and FT4 levels were measured every 6 weeks, and if enough serum was available extensive thyroid function tests (TFT) were additionally measured before start of treatment (t0), after 6 weeks (t6), and at the end of therapy. In addition, the effect of sorafenib on TH transport by monocarboxylate transporter (MCT) 8 or MCT10 was tested in transfected COS1 cells.
Results: Four patients (7%) developed thyroiditis. In the others, 30% had elevation of TSH or FT4 above the normal range. Overall, between t0 and t6, mean TSH increased from 1.28 to 1.57 mU/L (p<0.001) and mean FT4 from 18.4 to 21.2 pmol/L (p<0.001). Simultaneously, the serum T3/rT3 ratio decreased from 4.84 to 3.68 (p<0.001) and the (T3/T4) x100 ratio decreased from 1.88 to 1.58 (p=0.002). Sorafenib significantly decreased cellular T3 uptake by MCT8 and to a lesser extent by MCT10.
Conclusions: These in vivo data suggest that sorafenib affects TFT on multiple levels. Our in vitro experiments suggest a possible role of sorafenib-induced inhibition of T3 transport into the cell by MCT8 and MCT10.

PMID: 28575418 [PubMed - as supplied by publisher]

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