A novel therapeutic paradigm to treat congenital hypothyroidism


Paul Hofman, Department of Paediatric Endocrinology, Liggins Institute, 2–6 Park Ave, Grafton, Private Bag 92019, Auckland, New Zealand. Tel.: +64 9 3737599 ext 86453; Fax: +64 9 3738763; E-mail: p.hofman@auckland.ac.nz


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.

Design  Retrospective cohort study.

Patients  Infants with primary CH diagnosed by newborn screening.

Measurements  Treatment with L-T4 suspension initiated at 10, 12 and 15 µg/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.