Thyroid hormone resistance syndrome with P453T mutation in thyroid hormone receptor β gene

Rationale: Thyroid hormone resistance syndrome (THRS) is an inherited condition characterized by reduced responsiveness of target tissues to thyroid hormone. Due to their nonspecific symptomatic manifestations, these patients can be misdiagnosed. This study reports a pedigree with THRS caused by a mutation in the thyroid hormone receptor β (THRβ) gene. Patient concern: The proband, a 36-year-old woman at 19+4 weeks of gestation, was referred to our hospital because of abnormal thyroid function results. She was diagnosed with hyperthyroidism in October 2015, and had been treated with methimazole until her pregnancy. Diagnosis: The proband and 2 of her children were diagnosed with THRS based on genetic analysis. Sequence analysis of the THRβ gene showed a heterozygous mutation C>A located at exon 10. The mutation results in a change in proline for threonine at amino acid position 453, P453T. Interventions: No treatment will fully and specifically correct the defect. All 3 patients were in normal metabolic status, and thus treatment was not required. Outcomes: During a 2-year follow-up period, none of them had any complaints. The 20-year-old son (167 cm in height) and the 18-year-old daughter (150 cm in height) both had low academic performance. Lessons: Elevated serum thyroid hormone (TH) levels associated with nonsuppressed thyroid-stimulating hormone (TSH) levels usually leads to the diagnosis of THRS. Genetic analysis provides a short cut to diagnosis and the treatment should be based on the patient's clinical manifestations.