Endocrine Abstracts

Background: Resistance to thyroid hormone (RTH) is a rare disorder, most often caused by pathogenic variants in the THRB gene, characterised by elevated circulating thyroid hormones with non-suppressed or elevated thyroid-stimulating hormone (TSH). Clinical presentations range from asymptomatic goitre to mixed features of hypo- and hyperthyroidism, with significant inter-individual variability.

Case Presentation: A 78-year-old Caucasian woman presented with new-onset atrial fibrillation (AF) and fast ventricular response. Initial thyroid function tests revealed elevated free thyroxine (fT4) with normal TSH. She re-presented within one week with recurrent palpitations, gastrointestinal symptoms, and mild weight loss. Repeat investigations confirmed persistently elevated fT4 and free triiodothyronine (fT3) with non-suppressed TSH. Autoimmune thyroid disease was excluded, and radionuclide imaging demonstrated multinodular goitre with retrosternal extension. Despite carbimazole therapy, thyroid hormone levels remained high. Further evaluation ruled out assay interference and TSH-secreting pituitary adenoma (normal alpha subunit, unremarkable pituitary MRI). Genetic testing identified a heterozygous THRB c.959 G>C (p.Arg320 Pro) variant, classified as likely pathogenic, confirming RTH. Carbimazole was discontinued. The patient unfortunately died several weeks later from unrelated causes.

Discussion: This case illustrates a late-onset presentation of genetically confirmed RTH complicated by AF. The coexistence of multinodular goitre and AF initially suggested toxic nodular disease, delaying recognition of RTH. Cardiovascular manifestations are uncommon in RTH, but tissue-specific variability in thyroid hormone receptor expression may explain susceptibility in selected patients.

Conclusion: RTH should be considered in patients with elevated thyroid hormones and non-suppressed TSH after exclusion of secondary causes. Early endocrine involvement and genetic testing are crucial to avoid unnecessary antithyroid therapy and to guide family counselling.