Long-Term 3,5,3′-Triiodothyroacetic Acid Therapy in a Child with Hyperthyroidism Caused by Thyroid Hormone Resistance: Pharmacological Study and Therapeutic Recommendations

Abstract

The effectiveness of short-term 3,5,3'-triiodothyroacetic acid (TRIAC) therapy for the treatment of hyperthyroidism caused by thyroid hormone resistance (RTH) has been documented. Here, we report a 3-year course of TRIAC therapy in an RTH boy, with a quantitative evaluation of the therapeutic effects and pharmacological study of TRIAC. The gene encoding the thyroid hormone receptor beta (THRB) of the patient carries a P453T mutation. During treatment with up to 3.0 mg TRIAC per day, reduction in the thyroid volume, resolution of supraventricular arrhythmia, and decrease in thyroid-stimulating hormone (TSH) and free-thyroxine (FT4) levels were achieved. In addition, attention-deficit hyperactivity disorder (ADHD) symptoms improved, with a concomitant decline in the ADHD Rating Scale score. A TRIAC pharmacokinetic study, conducted using triiodothyronine level as a surrogate for TRIAC level, demonstrated that TRIAC disappears from the circulation rapidly and has a shorter duration of TSH secretion inhibitory effect in the RTH patient compared to that in the control subject. Studies of TSH and FT4 levels over a period of 3 years indicated that the TRIAC effect is dose dependent. TRIAC was effective and safe in ameliorating the effects of hyperthyroidism and ADHD symptoms in a child with known genetic RTH. Further, it was demonstrated that TRIAC has a short half-life and functions dose dependently.