Peripheral markers of thyroid function: the effect of T4 monotherapy vs T4/T3 combination therapy in hypothyroid subjects in a randomized crossover study

Background: A recent randomized controlled trial suggests that hypothyroid subjects may find levothyroxine (L-T-4) and levotriiodothyronine combination therapy to be superior to L-T-4 monotherapy in terms of quality of life, suggesting that the brain registered increased T-3 availability during the combination therapy. Hypothesis: Peripheral tissue might also be stimulated during T-4/T-3 combination therapy compared with T-4 monotherapy. Methods: Serum levels of sex hormone-binding globulin (SHBG), pro-collagen-1-N-terminal peptide (PINP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (representing hepatocyte, osteoblast, and cardiomyocyte stimulation respectively) were measured in 26 hypothyroid subjects in a double-blind, randomized, crossover trial, which compared the replacement therapy with T-4/T-3 in combination (50 mu g T-4 was substituted with 20 mu g T-3) to T-4 alone (once daily regimens). This was performed to obtain unaltered serum TSH levels during the trial and between the two treatment groups. Blood sampling was performed 24 h after the last intake of thyroid hormone medication. Results: TSH remained unaltered between the groups ((median) 0.83 vs 1.18 mU/l in T-4/T-3 combination and T-4 monotherapy respectively; P = 0.534). SHBG increased from (median) 75 nmol/l at baseline to 83 nmol/l in the T-4/T-3 group (P = 0.015) but remained unaltered in the T-4 group (67 nmol/l); thus, it was higher in the T-4/T-3 vs T-4 group (P = 0.041). PINP levels were higher in the T-4/T-3 therapy (48 vs 40 mu g/l (P < 0.001)). NT-proBNP did not differ between the groups. Conclusions: T-4/T-3 combination therapy in hypothyroidism seems to have more metabolic effects than the T-4 monotherapy.