title: Characteristics of patients with late manifestation of resistance thyroid hormone syndrome: a single-center experience.
abstract: Resistance to thyroid hormone (RTH) is a rare genetic disease caused by reduced tissue sensitivity to thyroid hormone. The hallmark of RTH is elevated serum levels of thyroid hormone with unsuppressed thyrotropin (TSH). However, the most common form of RTH results from minor defects in the ligand-binding domain or hinge domain of the TRβ gene, resulting in impaired T3-induced transcriptional activity, often showing mild presentation. Early diagnosis can be challenging. The objective of the current study was to characterize this specific group of RTH patients. This was a retrospective study. Patients diagnosed as RTH with TRβ mutations were enrolled in a single institute between 2004 and 2014. A total of 14 patients were diagnosed as RTH with mutation in THβ gene. The median age at diagnosis was 22.5 (IQR: 13.25-32.75). Goiter was the most common clinical finding. TSH was significantly elevated after TRH injection (median peak was 21.83 μIU/l, IQR: 13.59-31.48), 9.2-fold compared to the basal level. We found 10 mutations in TRβ gene, all located in the last four exons, and including one novel mutation, H271D. In vitro study found that H271D mutation reduced TR affinity to T3. Four patients with intact thyroid were diagnosed after 16 years old, defined as late manifestation. Compared to those diagnosed before 10 years old, patients with late manifestation presented with normal growth and mental development. Interestingly, three of them carried R438H mutation. We identified a novel p.H271D mutation in TRβ associated with RTH. Endocrinologists should be alert that RTH is frequently found in euthyroid patients with mild symptoms and often leads to misleading diagnosis as well as inappropriate treatment.
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, People's Republic of China.
authors.forename: Rulai
authors.initials: R
authors.lastname: Han
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, People's Republic of China. lei.yelei@gmail.com.|Shanghai Key Laboratory for Endocrine Tumors and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, 197 Ruijin 2nd Road, Shanghai, 200025, People's Republic of China. lei.yelei@gmail.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Ye
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, People's Republic of China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, People's Republic of China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, INRA, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364, Lyon Cedex 07, France.
authors.forename: Cyrielle
authors.initials: C
authors.lastname: Billon
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, INRA, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364, Lyon Cedex 07, France.
authors.forename: Wenyue
authors.initials: W
authors.lastname: Guan
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, INRA, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364, Lyon Cedex 07, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Gauthier
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, People's Republic of China.
authors.forename: Weiyuan
authors.initials: W
authors.lastname: Fang
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, People's Republic of China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, INRA, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364, Lyon Cedex 07, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Samarut
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, People's Republic of China.|Laboratory for Endocrine & Metabolic Diseases of Institute of Health Science, Shanghai Jiaotong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 227 South Chong Qing Road, Shanghai, 200025, People's Republic of China.
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D018776:Genes, erbA; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D012189:Retrospective Studies; D018382:Thyroid Hormone Resistance Syndrome / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult
keywords: H271D; Resistance to thyroid hormones; Thyroid hormone receptor beta gene (THRβ)