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Sorafenib-induced hypothyroidism is associated with increased type 3 deiodination
Randa M Abdulrahman1, Herman Verloop, Hendrieke Hoftijzer
1Department of Endocrinology, C4-R, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
The Journal of Clinical Endocrinology and Metabolism
|May 21, 2010
Summary
Sorafenib treatment in athyreotic patients with thyroid cancer decreases thyroid hormone levels by increasing their metabolism. This suggests sorafenib enhances type 3 deiodination, impacting thyroid hormone balance.
Area of Science:
- Endocrinology
- Oncology
- Pharmacology
Background:
- Tyrosine kinase inhibitors (TKIs) are linked to thyroid dysfunction.
- Athyreotic patients with thyroid cancer on TKIs show reduced thyroid hormone levels.
- This suggests TKIs may affect thyroid hormone metabolism.
Purpose of the Study:
- To investigate the impact of sorafenib on serum thyroid hormone concentrations.
- To assess the effect of sorafenib on iodothyronine deiodination in athyreotic patients.
Main Methods:
- Prospective, open-label, single-center study over 26 weeks.
- Measured serum thyroxine (T4), free T4, 3,5,3-triiodothyronine (T3), free T3, reverse T3 (rT3), and TSH.
- Calculated T3/T4 and T3/rT3 ratios to reflect iodothyronine deiodination.
Main Results:
- Adjusted serum free T4 and T3 levels decreased by 11% and 18%, respectively.
- TSH levels increased, while T3/T4 and T3/rT3 ratios decreased by 18% and 22%.
- These changes indicate enhanced type 3 deiodination.
Conclusions:
- Sorafenib treatment accelerates thyroid hormone (T4 and T3) metabolism.
- This effect is likely due to increased activity of type 3 deiodinase.
- Sorafenib influences thyroid hormone homeostasis in athyreotic patients.
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