Thyroxine Treatment of Adult RTHα Patients: Safety, Efficacy, and Metabolomic Changes

BACKGROUND: Resistance to thyroid hormone alpha (RTHα) is a rare genetic disorder with symptoms of hypothyroidism, but normal or close-to-normal thyroid function tests. Treatment with levothyroxine (L-T4) may be beneficial. This study investigated the efficacy, safety and biochemical changes of high-dose L-T4 and liothyronine (L-T3) treatment. METHODS: Four RTHα (Ala263Val) patients were treated with L-T4 (1.75 µg/kg) in a pilot open-label study and monitored for three years. Quality of life (QoL) was assessed using ThyPro. Analysis of auxiological- and biochemical-parameters, bone mineral density (BMD) and exploratory metabolomics was performed. A partial replacement of L-T4 with L-T3 was attempted. RESULTS: Treatment with L-T4 increased FT4, FT3, and rT3 to supraphysiological concentrations (relative to reference intervals) and suppressed thyroid-stimulating hormone with no adverse effects. Heart rate, bone markers, and sex hormone-binding globulin transiently increased. Several classes of lipids were reduced. BMD appeared unaltered. Patients reported improved QoL. One patient presented a short non-sustained ventricular tachycardia on L-T3 + L-T4. CONCLUSIONS: L-T4 treatment of adult RTHα patients was safe and improved QoL in adherent patients.