The Challenges and Complexities of Thyroid Hormone Replacement

Hypothyroidism is an endocrine disorder affecting 1%-10% of the population. Symptoms of hypothyroidism include fatigue, lethargy, and decreased cognitive performance. The mainstay therapy for hypothyroidism is synthetic thyroxine (T4) because of its long half-life and conversion to the bioactive form 3-5-3' triiodothyronine (T3). Recently, treatment research has re-emerged from clinicians who found that patients still experienced significant psychological morbidity, such as decreases in cognitive performance, mood, and physical status, despite appropriate standard T4 therapy. It was subsequently reported that patients treated with both T3 and T4 experienced better cognitive functioning compared to patients treated with T4 alone. This review discusses the current literature comparing cognitive improvement in combination T3/T4 therapies to T4 monotherapy in the context of the most recent biological research on thyroid metabolism and signaling in neurons that might help explain the conflicting cognitive results in these studies and help develop new paradigms to test in the future.