Hormonal replacement for children with severe primary hypothyroidism frequently results in irritability, poor concentration, and school difficulties. We reviewed our experience treating 14 severely hypothyroid children and adolescents (T4<2.1 mcg/dl) age 4.4 to 17.2 years (mean 12.2 years) with initial low-dose l-thyroxine. Initial dose was 25 mcg/day, increasing by 25 mcg increments at 6 week intervals to 75 mcg/day. Further increases were titrated according to thyroid function tests.

Three patients had achieved final height prior to treatment. For the remainder, initial 2-4 month growth velocity was 7.1± 2.4 cm/yr (mean± 1 SD) (range 4.1-10.8), and 5-7 month growth velocity 8.5 ± 1.9 cm/yr (range 5.7-10.9) with a growth velocity z score of 1.5 ± 1.7(range 0.2-4.9). TSH for all patients at 2-4 months was 61.6 ± 64.5 mIu/ml (range 2.1-196) and at 5-7 months 16.2 ± 14.3 mIu/ml (0.4-45.8). Restlessness and mood changes were seen in the children but not the adolescents, and were minor and transient. One child, however, developed pseudotumor cerebri. The dose of l-thyroxine to normalization of TSH was 1.8± 0.74 mg/Kg (range 0.9-3.4) or 52.2 ± 17.2 mg/m2(27.3-97.7).

Satisfactory growth was achieved over 6 months despite biochemical hypothyroidism. The dose of l-thyroxine required to achieve euthyroidism was lower than previously reported for children and adolescents on chronic treatment, suggesting initial heightened pituitary-hypothalamic sensitivity to l-thyroxine. Side effects of therapy were minor, although the risk of pseudotumor cerebri was not eliminated. We suggest that this be the preferred means of treatment for severe pediatric primary hypothyroidism. We speculate that even lower initial dosing may prevent pseudotumor cerebri.