Initial treatment dose of L-thyroxine in congenital hypothyroidism

J Pediatr. 2002 Dec;141(6):786-92. doi: 10.1067/mpd.2002.128887.


Objectives: To determine the optimal initial treatment dose of L-thyroxine in congenital hypothyroidism (CH) by evaluating the time course of rise of thyroxine (T(4)) and free T(4) concentrations into an established "target range" and normalization of thyroid-stimulating hormone (TSH) and to reevaluate the "target range" for T(4) and free T(4) concentrations during the first 2 weeks of CH treatment.

Study design: Infants of birth weight 3 to 4 kg with CH (n = 47) detected by newborn screening were randomly assigned into three L-thyroxine treatment dose arms: 37.5 microg/day (group 1); 62.5 microg/day for 3 days, then 37.5 microg/day (group 2); and 50 microg/day (group 3). Serum T(4), free T(4), triiodothyronine (T(3)), free T(3), and TSH were measured before treatment and at 3 days and 1, 2, 4, 8, and 12 weeks after treatment.

Results: T(4) and free T(4) concentrations increased into the target range (10 to 16 microg/dL) by 3 days of therapy in infants in groups 2 and 3 and by 1 week in group 1; 50 microg/day (average 14.5 microg/kg/day) provided the most rapid normalization of TSH by 2 weeks. With the use of linear regression analysis of T(4) versus TSH or free T(4) versus TSH plots, the intercept at the lower range of normal for TSH (1.7 mU/L) showed T(4) = 19.5 microg/dL and free T(4) = 5.23 ng/dL.

Conclusions: Initial dosing of 50 microg/day (12-17 microg/kg per day) raised serum T(4) and free T(4) concentrations to target range by 3 days and normalized TSH by 2 weeks of therapy. We recommend consideration of a somewhat higher "target range" of 10 to 18 microg/dL for T(4) and 2 to 5.0 ng/dL for free T(4) during the first 2 weeks of L-thyroxine treatment. After 2 weeks of treatment, the target range drops to 10 to 16 microg/dL for T(4) and 1.6 to 2.2 for free T(4).

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Congenital Hypothyroidism*
  • Humans
  • Hypothyroidism / drug therapy*
  • Infant, Newborn
  • Linear Models
  • Neonatal Screening
  • Reference Values
  • Thyroid Function Tests
  • Thyroid Hormones / blood
  • Thyrotropin / blood
  • Thyroxine / administration & dosage*
  • Thyroxine / blood
  • Thyroxine / therapeutic use


  • Thyroid Hormones
  • Thyrotropin
  • Thyroxine