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

• Published in: The journal of clinical endocrinology and metabolism 2020-02, Vol.105 (2), p.399-406
• Main Authors: Yoshida, Tomohiko, Nakayama, Akitoshi, Tamura, Ai, Higuchi, Seiichiro, Sakuma, Ikki, Nagano, Hidekazu, Felizola, Saulo Ja, Hashimoto, Naoko, Takemoto, Minoru, Tatsuno, Ichiro, Koide, Hisashi, Yokote, Koutaro, Tanaka, Tomoaki
• Format: Article
• Language: English
• Subjects: Aged, 80 and over; ATP Binding Cassette Transporter, Subfamily G, Member 2 - metabolism; Blood pressure; Carrier proteins; Case studies; Daunomycin; Drug resistance; Drug Resistance, Multiple - genetics; Drug therapy; Female; Gene expression; Hashimoto Disease - drug therapy; Hashimoto Disease - genetics; Health aspects; Humans; Hypothyroidism; Idiopathic thrombocytopenic purpura; Infectious diseases; Leukocytes; Lymphocytes; Multidrug resistance; Neoplasm Proteins - metabolism; Oral administration; Peripheral blood; Physiological aspects; Small intestine; Tablets; Thrombocytopenia; Thyroid; Thyroid-stimulating hormone; Thyroiditis; Thyroiditis, Autoimmune; Thyroxine; Thyroxine - therapeutic use; Treatment resistance
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgz073

Abstract Context 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. Case Description 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. Conclusions 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.