Literature DB >> 20484486

Sorafenib-induced hypothyroidism is associated with increased type 3 deiodination.

Randa M Abdulrahman1, Herman Verloop, Hendrieke Hoftijzer, Erik Verburg, Guido C Hovens, Eleonora P Corssmit, Christoph Reiners, Hans Gelderblom, Alberto M Pereira, Ellen Kapiteijn, Johannes A Romijn, Theo J Visser, Johannes W Smit.   

Abstract

BACKGROUND: Therapy with tyrosine kinase inhibitors is associated with thyroid dysfunction. Decreased serum thyroid hormone levels during tyrosine kinase inhibitors are also observed in athyreotic patients with thyroid carcinoma. We therefore hypothesized that tyrosine kinase inhibitors may influence thyroid hormone metabolism. AIM: The aim was to study the effects of sorafenib therapy on serum thyroid hormone concentrations and iodothyronine deiodination in athyreotic patients.
DESIGN: The design included a prospective open, single-center, single-arm 26-wk study.
METHODS: We measured serum thyroxine (T4), free T4, 3,5,3-triiodothyronine (T3), free T3, reverse T3 (rT3), and TSH concentrations at baseline and after 26 wk in 21 patients with progressive nonmedullary thyroid carcinoma treated with sorafenib. Ratios of T3/T4 and T3/rT3, which are independent of substrate availability and reflect iodothyronine deiodination, were calculated.
RESULTS: Serum free T4 and T3 levels, adjusted for levothyroxine dose per kilogram body weight, decreased by 11 and 18%, respectively, whereas TSH levels increased. The serum T3/T4 and T3/rT3 ratios decreased by 18 and 22%, respectively, which is compatible with increased type 3 deiodination.
CONCLUSIONS: Sorafenib enhances T4 and T3 metabolism, which is probably caused by increased type 3 deiodination.

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Year:  2010        PMID: 20484486     DOI: 10.1210/jc.2009-2507

Source DB:  PubMed          Journal:  J Clin Endocrinol Metab        ISSN: 0021-972X            Impact factor:   5.958


  30 in total

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2.  Thyroid function: Sorafenib alters metabolism of T3.

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Review 3.  2019 European Thyroid Association Guidelines for the Treatment and Follow-Up of Advanced Radioiodine-Refractory Thyroid Cancer.

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Review 8.  Tyrosine kinase inhibitors: their on-target toxicities as potential indicators of efficacy.

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Review 10.  Clinical review: kinase inhibitors: adverse effects related to the endocrine system.

Authors:  Maya B Lodish
Journal:  J Clin Endocrinol Metab       Date:  2013-02-28       Impact factor: 5.958

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