Effect of Different Starting Doses of Levothyroxine on Growth and Intellectual Outcome at Four Years of Age in Congenital Hypothyroidism

To evaluate the effect of different initial levothyroxine (LT₄) replacement doses on growth and intellectual outcome in patients with congenital hypothyroidism (CH) detected by neonatal screening program, the longitudinal growth and intelligence quotient (IQ) were assessed and compared at 4 years of age in 83 patients with CH. The patients were divided into three groups according to the initial LT₄ dose used: (1) group 1 (n = 42) received the previously recommended dose of 6.0-8.0 μg/kg per day; (2) group 2 (n = 21) received a dose of 8.1-10.0 μg/kg per day; (3) Group 3 (n = 20) a dose of 10.1-15.0 μg/kg per day. The IQ, evaluated by the Wechsler Preschool and Primary Scale of Intelligence test at 4 years of age, was significantly higher in group 3 (IQ 98 ± 9) compared to group 1 (IQ 88 ± 13; p < 0.05) but not compared to group 2 (IQ 94 ± 13). However, the IQs were below the normal range (< 85) in six patients from group 2 (28%), but in none of the patients from group 3 (p = 0.03). Patients from group 3, with severe CH at diagnosis, had an IQ (97 ± 9) at 4 years of age, which was not different from that of patients from the same group with moderate CH at diagnosis (IQ 99 ± 9). Similar results were also observed in patients from group 2 however, mean IQ scores in these patients(93 ± 12) were several points lower than those observed in patients from group 3 (95 ± 15). After the first month of treatment, optimal serum levels of thyroxine (T4) and free thyroxine (FT₄) were achieved in all groups, however, only patients from group 3 were able to normalize thyrotropin (TSH) (group 1, 16.0 ± 12.0; group 2, 9.2 ± 10.0; and group 3, 2.4 ± 3.3 mU/L; p< 0.0001). Twelve patients from group 2 treated with an initial LT₄ dose above 9 μg/kg per day were able to normalize TSH levels within the first 3 months of life and this resulted in a better IQ (97 ± 16) compared to the remaining patients from the same group (IQ 90 ± 9). In the whole group of 83 patients the IQ at 4 years of age was positively correlated to both initial LT₄ dosage (r = 0.27, p < 0.02) and FT₄ concentrations after the first month of treatment (r = 0.29, p < 0.02), and negatively correlated to TSH concentrations after the first month of treatment (r = -0.27, p < 0.02). No significant differences were observed in height, weight, head circumference, and bone age maturation among the three groups of patients. No clinical signs or symptoms of overtreatment were observed during follow-up in patients receiving the higher LT₄ dosage. Our results indicate that high LT₄ starting doses rapidly normalize serum TSH concentrations resulting in an improvement of the IQ at 4 years of age, even in patients with severe CH at diagnosis. Growth and bone age maturation are not affected by such a high dose.