Replacement therapy with thyroxine plus triiodothyronine (14:1) is not superior to thyroxine alone with respect to the psychical and physical wellbeing of patients with hypothyroidism

Problem: There is evidence (NEJM 1999;340:424) that replacement therapy of hypothyroidism with levothyroxine (T4) combined with triiodothyronine (T3) may improve the wellbeing of patients. However, the study is still subject of controversial debate. Methods: Therefore, 23 hypothyroid patients (3 male, age 23–69 years, 21 after surgery or radioiodine, 2 with autoimmune thyroiditis) on long-term replacement therapy with 100–175µg T4/d were randomly allocated to a double-blind, two-period, cross-over trial to confirm superiority of a 12 week replacement therapy with a physiological combination of thyroid hormones (bioavailable molar T4/T3 ratio 14:1) over T4 allone with regard to psychological and physical wellbeing and cognitive performance as assessed by psychological standard tests. Results: Replacement therapy with T4 and T4/T3 was not different in all steady-state hormonal, metabolic and cardiovascular characteristics except thyrotrophic hormone (TSH) which was more suppressed after T4/T3. The area under the curve (AUC) of free T3 (fT3) was higher after T4/T3, of free T4 after administration of T4. The AUC of fT3 after T4/T3 but not after T4 was significantly correlated to serum TSH (r -0.609, p<0.05). The differences in thyroid hormone disposition were overall not associated with any significant changes in mood and cognitive functioning (Table). However, patients with autoimmune thyroid disease in history had significantly higher serum levels of fT3 after replacement with T4/T3 and clearly impaired mood and cognitive functioning. T4 T4/T3 TSH (mU/L) 1.5±1.3 0.5±0.6 (<0.001) Subjects with TSH <0,02 (N) 2 8 Digit Span Test (N) 12.13±2.46 12.39±2,78 Visual Scanning Test (s) 61.61±28.14 64.76±28.69 Global Mood Score 11.04±9.62 12.26±13.35 Conclusions: Replacement therapy of hypothyroidism with a psychological combination of levothyroxine with triiodothyronine (14:1) does not improve mood and cognitive performance compared to levothyroxine alone.