Endocrine Abstracts

Despite normalized serum thyroid hormone levels, 10% of hypothyroid patients treated with levothyroxine (LT4) have persistent complaints, of which tiredness is the most commonly reported. This could be explained by the fact that the physiological T4/T3 ratio is not achieved with LT4 monotherapy. Studies have reported contradicting results as to whether the addition of liothyronine (LT3) is effective in relieving these persistent complaints. However, all of these studies suffer from one or more important limitations (e.g., patient selection, limited sample size, supraphysiological LT3 dose, limited follow-up time, non-validated questionnaires), hampering their interpretation. The T3-4-Hypo trial is a national, randomised, placebo-controlled, double-blind, multi-centre study in patients with auto-immune hypothyroidism and persistent complaints despite LT4 monotherapy. Patients are randomized to either LT4/lT3 combination therapy or LT4/placebo, and the primary endpoint is the ThyPRO tiredness subscale score at 52 weeks follow-up. In case of an effect, we will investigate whether effect sizes are higher in patients with genetic variations in a thyroid hormone converting enzyme (DIO2) and transporter (MCT10). Secondary analyses include effects on the most important thyroid hormone target organs including cardiovascular, metabolic, bone and neurocognitive outcomes. The first patient was enrolled in October 2022. The trial is still open for enrolment.