title: Peripheral markers of thyroid function: the effect of T4 monotherapy vs T4/T3 combination therapy in hypothyroid subjects in a randomized crossover study.
abstract: BACKGROUND
  A recent randomized controlled trial suggests that hypothyroid subjects may find levothyroxine (l-T4) and levotriiodothyronine combination therapy to be superior to l-T4 monotherapy in terms of quality of life, suggesting that the brain registered increased T3 availability during the combination therapy.
  
  
  OBJECTIVE
  Peripheral tissue might also be stimulated during T4/T3 combination therapy compared with T4 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 T4/T3 in combination (50 μg T4 was substituted with 20 μg T3) to T4 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 T4/T3 combination and T4 monotherapy respectively; P=0.534). SHBG increased from (median) 75 nmol/l at baseline to 83 nmol/l in the T4/T3 group (P=0.015) but remained unaltered in the T4 group (67 nmol/l); thus, it was higher in the T4/T3 vs T4 group (P=0.041). PINP levels were higher in the T4/T3 therapy (48 vs 40 μg/l (P<0.001)). NT-proBNP did not differ between the groups.
  
  
  CONCLUSIONS
  T4/T3 combination therapy in hypothyroidism seems to have more metabolic effects than the T4 monotherapy.
authors.affiliation: Endocrine Unit, Department of Medicine O Herlev University Hospital Herlev RingvejDK-2730, Herlev Denmark.
authors.forename: Ulla
authors.initials: U
authors.lastname: Schmidt
authors.forename: Birte
authors.initials: B
authors.lastname: Nygaard
authors.forename: Ebbe Winther
authors.initials: EW
authors.lastname: Jensen
authors.forename: Jan
authors.initials: J
authors.lastname: Kvetny
authors.forename: Anne
authors.initials: A
authors.lastname: Jarløv
authors.forename: Jens
authors.initials: J
authors.lastname: Faber
keywords: Thyroid hormones; extrathyroidal effects; substitution