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Bezafibrate induces hypothyroidism in a patient with resistance to thyroid hormone ß due to a G347R variant.
Yamauchi, Ichiro; Yamashita, Takafumi; Sugawa, Taku; Tagami, Tetsuya; Hanaoka, Ikuko; Usui, Takeshi; Hirota, Keisho; Hakata, Takuro; Ueda, Yohei; Fujii, Toshihito; Sakane, Yoriko; Yasoda, Akihiro; Inagaki, Nobuya.
Afiliação
  • Yamauchi I; Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Yamashita T; Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Sugawa T; Metabolism and Endocrinology Division of Internal Medicine, Kishiwada City Hospital, Osaka, Japan.
  • Tagami T; Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Hanaoka I; Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
  • Usui T; Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
  • Hirota K; Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan.
  • Hakata T; Metabolism and Endocrinology Division of Internal Medicine, Kishiwada City Hospital, Osaka, Japan.
  • Ueda Y; Department of Medical Genetics, Shizuoka General Hospital, Shizuoka, Japan.
  • Fujii T; Research Support Center, Shizuoka General Hospital, Shizuoka, Japan.
  • Sakane Y; Department of Pathology and Biology of Diseases, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Yasoda A; Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Inagaki N; Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Clin Endocrinol (Oxf) ; 96(2): 236-245, 2022 02.
Article em En | MEDLINE | ID: mdl-34519083
OBJECTIVE: A unique clinical course was observed in a patient with resistance to thyroid hormone ß (RTHß) caused by a variant of the THRB gene leading to the replacement of glycine with arginine in codon 347 (p.G347R). He presented with the syndrome of inappropriate secretion of thyrotropin (TSH) (free T4 [fT4]: 32.43 pmol/L, TSH: 4.67 mIU/L), but slowly developed progressive hypothyroidism (fT4: 8.37 pmol/L, TSH: 100.90 mIU/L) that resolved after suspending bezafibrate (BZ) treatment (fT4: 32.18 pmol/L, TSH: 7.14 mIU/L). This study clinically and experimentally evaluated this interesting phenomenon. METHODS: A retrospective cohort analysis of non-RTHß patients was performed at Kyoto University Hospital. Data before BZ treatment were compared to the first data after treatment. Using reporter assays of iodothyronine deiodinases (DIO1, DIO2, DIO3) in HEK293T cells, we performed functional analyses of mutant thyroid hormone receptor ß with p.G347R (G347R TRß). Mice with G347R TRß were generated by hydrodynamic gene delivery. RESULTS: In non-RTHß patients (n = 7), BZ treatment did not change serum free T3 and TSH but significantly increased fT4 (p = .008). BZ administration increased DIO3 reporter activity in the context of G347R TRß, whereas did not change DIO1 and DIO2 reporter activity. In the livers of mice with G347R TRß, BZ administration increased reverse T3 content, which corresponded to an increase in Dio3 messenger RNA. CONCLUSIONS: While hypothyroidism associated with BZ treatment did not occur in non-RTHß patients, it was observed in a patient with RTHß due to the p.G347R variant. Liver DIO3 upregulation might involve this hypothyroidism.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Bezafibrato / Hipotireoidismo Tipo de estudo: Observational_studies Limite: Animals / Humans / Male Idioma: En Revista: Clin Endocrinol (Oxf) Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Bezafibrato / Hipotireoidismo Tipo de estudo: Observational_studies Limite: Animals / Humans / Male Idioma: En Revista: Clin Endocrinol (Oxf) Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Japão