Initial treatment dose of L-thyroxine in congenital hypothyroidism

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 = 417) detected by newborn screening were randomly assigned into three L-thyroxine treatment dose arms: 37.5 mug/day (group 1); 62.5 mug/day for 3 days, then 37.5 mug/day (group 2); and 50 mug/day (group 3). Serum T-4, free T-4, trilodothyronine (T-3)1 31 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 mug/d L) by 3 days of therapy in infants in groups 2 and 3 and by 1 week in group 1; 50 mug/day (average 14.5 mug/kg/day) provided the most rapid normalization of TSH by 2 weeks. With the use of linear regression analysis of T4 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 mug/dL and free T-4 = 5.23 ng/dL. Conclusions: Initial dosing of 50 mug/day (12-17 pg/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 mug/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 mug/dL for T-4 and 1.6 to 2.2 for free T-4.