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Resistance to Thyroid Hormone (RTH) and Resistance to TSH (RTSH)

  • Alexandra M. Dumitrescu
  • Ronald N. Cohen
Chapter

Abstract

Resistance to thyroid hormone (RTH) is a syndrome characterized by variable tissue hyporesponsiveness to thyroid hormone (TH). Mutations in both TH receptors (THRA and THRB) isoforms have been identified and manifest different phenotypes of RTH, RTH-alpha, and RTH-beta. Patients with the RTH-beta phenotype seek medical attention for goiter, abnormal thyroid function tests (TFTs), or through neonatal screening programs. Biochemically, RTH-beta is characterized by elevated TH values in the setting of non-suppressed thyrotropin (TSH) levels. Resistance at the level of the hypothalamus and pituitary leads to elevated TSH, which stimulates the thyroid gland to increase production of TH; however, reduced action elsewhere results in compensated TH hyporesponsiveness to a lesser or greater degree depending on the predominant TH receptor (TR) isoform in the tissue, alpha (α) or beta (β). THRA gene mutations have remained elusive until recently. The first case of RTH-α was identified through whole genome sequencing. Because TRα is not involved in the feedback regulation of the hypothalamic-pituitary-thyroid axis, the TFTs are different from patients with RTH-β, namely, low or normal T4, high normal T3, and normal or slightly elevated TSH. These mild thyroid abnormalities lead patients to present themselves in non-endocrinological clinical departments.

The phenotype of resistance to TSH is characterized by high serum TSH in the absence of goiter. Patients are often identified at birth through neonatal screening for congenital hypothyroidism. Affected individuals have normal or hypoplastic thyroid glands, high serum TSH, and normal or low serum T4 and T3, and symptoms range from euthyroid hyperthyrotropinemia to overt hypothyroidism.

Keywords

Thyroid hormone receptor Resistance to thyroid hormone RTH-beta RTH-alpha Non-TR RTH Thyrotropin (TSH) TSH receptor Thyroid function tests Mutation Development MCT8 SBP2 Deiodinases 

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Medicine, Section of Adult and Pediatric Endocrinology, Diabetes, and MetabolismUniversity of ChicagoChicagoUSA

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