Does initial dosing of levothyroxine in infants with congenital hypothyroidism lead to frequent dose adjustments secondary to iatrogenic hyperthyroidism on follow-up?

Background: Congenital hypothyroidism (CH) is the most common preventable cause of intellectual disability. The recommended starting dose of levothyroxine (LT4) is between 10 and 15 mu g/kg, an extremely wide range. We hypothesized that a sizable proportion of newborns treated for CH at the higher end of the dosage range become biochemically hyperthyroid at a follow-up visit. Methods: This study is a retrospective chart review of infants with CH between 2002 and 2012. Results: Of the 104 patients included in this analysis, the average age at diagnosis was 11 days and the average starting dose of LT4 was 12 +/- 2.5 mu g/kg. At follow-up, 36.5% required a dose reduction because of iatrogenic hyperthy-roxinemia, 51% required no dose adjustment and 12.5% required a dose increase due to an elevated thyroid stimulating hormone (TSH). The starting doses of LT4 for those requiring a dose reduction, those not requiring an adjustment and those requiring an increase in the dose were 13.2 +/- 2.4, 11.5 +/- 2.1 and 10.3 +/- 2.6 mu g/kg/day, respectively (p = 0.0001). Of the 34% of infants treated with an initial dose of > 12.5 mu g/day, 57.1% required a dose reduction at follow-up, compared to 26.1% of those whose initial starting dose was <= 12.5 mu g/kg/day (p = 0.007). Conclusions: Following the guidelines for initiating therapy for CH, 36.5% of the infants required a dose reduction for iatrogenic hyperthyroxinemia. These infants received a higher dose of LT4 than the infants who either required no adjustment or required an increase in the dose. A narrower range for initial dosing in CH may be appropriate.