title: Resistance to thyroid hormone accompanied by Graves' disease.
abstract: Resistance to thyroid hormone (RTH) is characterized by elevated serum levels of thyroid hormones and normal or slightly increased serum thyrotropin (TSH) levels. Recently it has been suggested that chronic TSH stimulation in RTH activates intrathyroidal lymphocytes, leading to thyroid damage and autoimmune thyroid disease (AITD). Therefore, individuals with RTH have an increased likelihood of AITD compared to unaffected relatives. We here report a 33-year-old woman in whom we diagnosed Graves' disease and treated her with thiamazole (MMI). For two years, her TSH levels were suppressed when thyroid hormones were elevated and conversely they were increased when thyroid hormones levels were decreased. These findings were common for a clinical course during treatment for Graves' disease with anti-thyroid drug. However, three years after the initiation of MMI therapy, she had a normal or gradually elevated serum TSH level even though the level of thyroid hormones never decreased, indicating inappropriate secretion of TSH. We concluded she had RTH clinically, and we demonstrated by direct sequence analysis a mutation of the TRβ gene, causing replacement of a glycine (G) with arginine (R) at codon 251. The finding of an elevated TSH level without decreased thyroid hormones should suggest the presence of RTH during therapy of Graves' disease.
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Japan.
authors.forename: Tsuguka
authors.initials: T
authors.lastname: Shiwa
authors.forename: Kenji
authors.initials: K
authors.lastname: Oki
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Awaya
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nakanishi
authors.forename: Kiminori
authors.initials: K
authors.lastname: Yamane
mesh_terms: D000328:Adult; D013956:Antithyroid Agents / Q000627:therapeutic use; D015897:Comorbidity; D005260:Female; D018776:Genes, erbA / Q000235:genetics; D006111:Graves Disease / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology*; D006801:Humans; D008713:Methimazole / Q000627:therapeutic use; D009154:Mutation / Q000235:genetics; D018382:Thyroid Hormone Resistance Syndrome / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics; D013972:Thyrotropin / Q000097:blood
chemical_list: D013956:Antithyroid Agents; D008713:Methimazole; D013972:Thyrotropin