A novel therapeutic paradigm to treat congenital hypothyroidism.
OBJECTIVE
To determine the effectiveness of a novel therapeutic paradigm to treat congenital hypothyroidism (CH) incorporating variable initial doses of L-T4 based on the underlying aetiology and frequent monitoring, up to 2 years of age.


METHODS
Retrospective cohort study.


METHODS
Infants with primary CH diagnosed by newborn screening.


METHODS
Treatment with L-T4 suspension initiated at 10, 12 and 15 microg/kg/day for dyshormonogenesis, ectopia and athyreosis, respectively. Serum TSH and free T4 (FT4) levels monitored weekly during the first 4 weeks, at 6 weeks, thereafter monthly during the first 2 years. Dose changes were made to keep FT4 level in upper half of the normal range.


RESULTS
Sixty-nine infants; 17 had dyshormonogenesis, 35 ectopia and 17 athyreosis. Seventy-eight percent of subjects normalized FT4 levels within 7 days of treatment and 100% within 14 days. TSH levels normalized in 26% of infants within 7 days and in 92% by 21 days. Supraphysiological levels of FT4 were noted in 28% of infants, for a maximum of 2 weeks. 48% infants needed one dose adjustment and 30% needed at least two in the first month. In 52 infants over the first 2 years, mean FT4 levels were consistently in the upper half of the normal range. Two or more dose adjustments every 3 months were made 57 times in the first year as compared to 19 times in the second year.


CONCLUSIONS
A variable initial dose paradigm based on aetiology with frequent testing and using T4 suspension rapidly normalizes FT4 levels without producing persistent hyperthyroxinaemia.
Mathai
Sarah
S
Paediatric Endocrinology, Liggins Institute, University of Auckland and Starship Children's Health, Auckland, New Zealand.
Cutfield
Wayne S
WS
Gunn
Alistair J
AJ
Webster
Dianne
D
Jefferies
Craig
C
Robinson
Elizabeth
E
Hofman
Paul
P
D000465:Algorithms; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003409:Congenital Hypothyroidism / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D054796:Drug Dosage Calculations; D005260:Female; D005500:Follow-Up Studies; D020249:Hormone Replacement Therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening; D012189:Retrospective Studies; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000008:administration & dosage* / Q000097:blood; D013997:Time Factors
D013972:Thyrotropin; D013974:Thyroxine