Treatment

Levothyroxine (l-T4) given orally is the treatment of choice. Although T3 is the biologically active form
of thyroid hormone, most of the T3 in the brain is formed from local deiodination of T4. Because 80%
of circulating T3 is formed by monodeiodination of T4, serum levels of T4 and T3 return to normal with
l-T4 treatment alone. The recommended initial starting dose is 10-15 μg/kg/day (totaling 37.5-50.0
μg/ day for most term infants). The starting dose can be tailored to the severity of hypothyroidism.
Rapid normalization of thyroid function has been demonstrated to be important in achieving optimal
neurodevelopmental outcome. Newborns with more severe hypothyroidism, as judged by a serum T4
<5 μg/dL and/or imaging studies confirming aplasia, should be started at the higher end of the dosage
range.

l-T4 is available only in tablet form in the United States; there is an approved liquid l-T4 preparation
in Europe. The daily tablets should be crushed and mixed with a small volume of liquid. l-T4 tablets
should not be mixed with soy protein formulas, concentrated iron, or calcium, because these can bind
T4 and inhibit its absorption. Although it is recommended to administer l-T4 on an empty stomach
and avoid food for 30-60 min, this is not practical in an infant. As long as the method of administration
is consistent day to day, dosing can be adjusted based on serum thyroid test results to achieve the
desired treatment goals.

Levels of serum T4 or free T4 and TSH should be monitored at recommended intervals (every 1-2 mo
in the 1st 6 mo of life, and then every 2-4 mo between 6 mo and 3 yr of age). The goals of treatment
are to maintain the serum free T4 or total T4 in the upper half of the reference range for age (see
Table 565-2), with serum TSH in the reference range for age, optimally 0.5-2.0 mU/L. The dose of l-T4
on a weight basis gradually decreases with age.

Later, confirmation of the diagnosis may be necessary for some infants to rule out the possibility of
transient hypothyroidism. This is unnecessary in infants with proven thyroid ectopia or in those who
manifest elevated levels of TSH after 6-12 mo of therapy because of poor compliance or an inadequate
dose of T4. Discontinuation of therapy at about 3 yr of age for 3-4 wk results in a marked increase in
TSH levels in children with permanent hypothyroidism.

Care should be taken to avoid prolonged undertreatment or overtreatment. The only untoward effects
of l-T4 are related to its dosage. Overtreatment can risk craniosynostosis and temperament problems.