Initial treatment dose of L-thyroxine in congenital hypothyroidism.
OBJECTIVE
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.


METHODS
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).
Selva
Karin A
KA
Department of Pediatrics, Oregon Health and Sciences University, Oregon State Public Health Laboratories, and Northwest Kaiser Permanente, Portland, Oregon, USA.
Mandel
Scott H
SH
Rien
Leanne
L
Sesser
David
D
Miyahira
Richard
R
Skeels
Michael
M
Nelson
Jerald C
JC
Lafranchi
Stephen H
SH
D003409:Congenital Hypothyroidism; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy*; D007231:Infant, Newborn; D016014:Linear Models; D015997:Neonatal Screening; D012016:Reference Values; D013960:Thyroid Function Tests; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use
D013963:Thyroid Hormones; D013972:Thyrotropin; D013974:Thyroxine