A Case of Hashimoto's Thyroiditis with Multiple Drug Resistance and High Expression of Efflux Transporters.

The Journal of clinical endocrinology and metabolism 2020 Feb 01

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Hashimoto's thyroiditis is the most common cause of hypothyroidism. Patients usually respond well to oral synthetic thyroxine (levothyroxine); however, for unknown reasons some individuals present with treatment-resistant Hashimoto thyroiditis. In cases of cancer and certain infectious diseases, the ATP binding cassette (ABC) transporters have been implicated in multidrug resistance, and we hypothesized and investigated a role of ABC transporters in drug-resistant Hashimoto's thyroiditis. The patient whose case we report had a history of Hashimoto's thyroiditis, immune thrombocytopenia, and refractory hypertension, with varying treatment resistance to the oral medications prescribed for each condition. In order to establish or exclude a genetic basis for her illness, we examined the patient's gene expression profiles using peripheral blood leukocytes, and found that ABCG2/BCRPexpression was significantly high compared with healthy volunteers. Also, the increased daunomycin efflux capacity of our patient's lymphocytes was successfully inhibited by fumitremorgin C, a specific ABCG2/BCRP inhibitor, and the patient's level of thyroid-stimulating hormone increased by 248.6% after administration of intact levothyroxine tablets but decreased by 45.1% when tablets were crushed. Her average blood pressure decreased from 166.3/108.5 mmHg to 125.9/78.8 mmHg when switching from intact to crushed losartan tablets. High expression and accelerated efflux transporter activity of ABCG2/BCRP in the small intestine are expected to contribute to the ineffectiveness of orally administered intact tablets in cases with treatment-resistant Hashimoto's thyroiditis, and crushed tablets can be more effective for some of these patients. © Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Citation

Tomohiko Yoshida, Akitoshi Nakayama, Ai Tamura, Seiichiro Higuchi, Ikki Sakuma, Hidekazu Nagano, Saulo Ja Felizola, Naoko Hashimoto, Minoru Takemoto, Ichiro Tatsuno, Hisashi Koide, Koutaro Yokote, Tomoaki Tanaka. A Case of Hashimoto's Thyroiditis with Multiple Drug Resistance and High Expression of Efflux Transporters. The Journal of clinical endocrinology and metabolism. 2020 Feb 01;105(2)