Experience in treating congenital hypothyroidism: Implications regarding free thyroxine and thyrotropin steady-state concentrations during optimal levothyroxine treatment

Background: A major problem in the treatment of patients with congenital hypothyroidism (CHT) is that the optimal individual target values of thyrotropin (TSH) and free thyroxine (fT4) are unknown. We investigated whether patients with CHT have during treatment considered optimal stable fT4 and TSH steady-state concentrations (SSCs) that can be used as target values, and whether TSH or fT4 is more useful in guiding decisions regarding therapy. Methods: From 60 early-treated patients with CHT, TSH and fT 4 follow-up samples within the age interval 1.5-132 months (postinitial period) and within TSH interval 0.5-10 mU/L were selected. TSH and fT4 SSCs were estimated by taking the individual mean values of a series of determinations, under the most euthyroid conditions possible (n=1257), for the whole age and TSH intervals, as well as for the age intervals 1.5-24, 25-72, and 73-132 months, as well as, for fT4, for the two split TSH intervals 0.5-4.49 and 4.5-10 mU/L. For all SSCs, the within-subject coefficient of variation (CVw) was determined. Further, fT4 SSCs were assessed for the first 6 weeks after therapy initiation. Results: For both TSH and fT4, individual SSCs differed significantly (p<0.001). The 95% confidence interval for TSH SSCs was 1.1-5.7 mU/L and for fT4 SSCs 16.6-28.7 pmol/L. Mean CVw values for TSH and fT4 SSCs were 60.9% and 13.1%, respectively. Individual fT4 and TSH SSCs were reproducible when assessed for the three age intervals, both slightly decreasing with age (p≤0.033), and fT4 SSCs were reproducible for the two split TSH intervals, with a slight fT4 difference (p<0.001). fT4 SSCs were largely independent of the administered LT4 dosage (range 2.4-6.1 μg/kg). fT4 SSCs of the initial period were comparable to those of postinitial period with a mean±SD difference of 1.0±3.5 pmol/L, p=0.07. Conclusions: Our study suggests that in CHT during therapy considered optimal, stable TSH and fT4 SSCs can be found slightly decreasing with age and largely independent of the administered LT4 dosage (range 2.4-6.1 μg/kg). In clinical follow-up, fT 4 SSCs may be more valuable as individual target values than TSH SSCs.

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