Peripheral markers of thyroid function: the effect of T(4) monotherapy vs T(4)/T(3) 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 μg T(4) was substituted with 20 μg 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 μg/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.