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J Clin Endocrinol Metab. 2017 Aug 1;102(8):2922-2929. doi: 10.1210/jc.2016-4025.

Sorafenib-Induced Changes in Thyroid Hormone Levels in Patients Treated for Hepatocellular Carcinoma.

Author information

1
Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus University Medical Center, 3000 CA Rotterdam, Netherlands.
2
Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 CA Rotterdam, Netherlands.
3
Department of Pathology, Erasmus University Medical Center, 3000 CA Rotterdam, Netherlands.
4
Department of Clinical Chemistry, Erasmus University Medical Center, 3000 CA Rotterdam, Netherlands.
5
Department of Epidemiology, Erasmus University Medical Center, 3000 CA Rotterdam, Netherlands.

Abstract

Context:

The pathogenesis of tyrosine kinase inhibitor-induced thyroid hormone (TH) alterations are still a matter of debate.

Objective:

The objective of this study was to determine the effects of sorafenib on TH levels in patients with hepatocellular carcinoma (HCC) and to evaluate possible mechanisms.

Design:

We performed a prospective cohort study between 2009 and 2016.

Setting:

This study was conducted at a tertiary referral center.

Patients:

This study included 57 consecutive patients with HCC who were treated with sorafenib.

Main Outcome Measure:

Thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels were measured every 6 weeks, and extensive thyroid function tests (TFTs) were measured before treatment (t0), after 6 weeks (t6), and at the end of therapy. 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. Among the other patients, 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 triiodothyronine (T3)/reverse triiodothyronine ratio and the (T3/thyroxine) ×100 ratio decreased. Sorafenib decreased cellular T3 uptake by MCT8 and to a lesser extent by MCT10.

Conclusions:

These in vivo data suggest that sorafenib affects TFTs 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
DOI:
10.1210/jc.2016-4025
[Indexed for MEDLINE]

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