A case of thyroid hormone resistance: a rare mutation

Area of Science:

• Endocrinology
• Genetics
• Rare Diseases

Background:

• Reduced sensitivity to thyroid hormones (RSTH) is a rare genetic disorder characterized by persistent hyperthyroxinemia with non-suppressed thyroid-stimulating hormone (TSH).
• It arises from impaired intracellular thyroid hormone (TH) action, affecting approximately 3,000 individuals globally.

Observation:

• A 67-year-old woman with a history of thyroidectomy presented with recurrent goiter and laboratory findings of persistent hyperthyroxinemia with non-suppressed TSH.
• Despite being clinically euthyroid, her thyroid function tests showed abnormal results, and TRH tests were normal.

Findings:

• Genetic analysis of the patient revealed a novel mutation in the THRB gene, specifically at codon 346 within the ligand-binding domain.
• The patient's son had normal thyroid function tests and genetic studies, indicating a sporadic mutation in this case.

Implications:

• RSTH diagnosis should be considered in euthyroid patients with hyperthyroxinemia.
• Management focuses on maintaining normal TSH levels and a eumetabolic state, alongside genetic counseling and prenatal diagnosis.
• Understanding these mutations is crucial to prevent inappropriate treatment that could lead to hypothyroidism.