Tyrosine kinase inhibitors and the thyroid as both an unintended and an intended target.
OBJECTIVE
To review the association of the tyrosine kinase inhibitor sunitinib with hypothyroidism as well as the mean time to onset, possible mechanisms, reversibility, and mean duration.


METHODS
We performed a MEDLINE search of the English-language literature using a combination of words ("sunitinib," "tyrosine kinase inhibitors," "thyroid," and "hypothyroidism") to identify original studies and reviews on sunitinib and thyroid function.


RESULTS
Hypothyroidism was reported in 36% to 46% of patients who took sunitinib in prospective studies. A higher incidence (53% to 85%) was reported in studies containing both retrospective and prospective data. The mean time to onset of hypothyroidism after initiation of sunitinib therapy ranged from 12 to 50 weeks. The risk of development of hypothyroidism appears to increase with the increasing duration of sunitinib therapy, and the condition is likely reversible once therapy has been discontinued.


CONCLUSIONS
Baseline thyroid function tests should be performed before the initiation of sunitinib treatment. Because hypothyroidism can develop early in the course of therapy, thyroid function tests should be monitored frequently throughout the duration of treatment. Possible mechanisms for thyroid dysfunction include impaired thyroid hormone synthesis, a destructive thyroiditis preceding the development of hypothyroidism, and increased thyroid hormone clearance. If hypothyroidism is identified, levothyroxine therapy should be promptly initiated.
Vetter
Marion L
ML
Division of Endocrinology, Diabetes, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19146, USA.
Kaul
Shailja
S
Iqbal
Nayyar
N