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The majority of patients require a dose of 100-200 µg T4 per day,
approximately 1.68 µg/kg/day. There is a positive correlation between
the severity of the thyroid failure, as evaluated by the concentration
of serum TSH, and the dose of T4 to restore euthyroidism. In patients in
whom hypothyroidism results from radical therapy for hyperthyroid Graves'
disease, autonomy of the thyroid residue may persist so that only a subnormal
dosage of T4 will be required.
Initiation of therapy should be adapted to the age and condition of the patient, and duration and severity of hypothyroidism. In young healthy adults, L-T4 is generally instituted at a dose of 50-75 µg per day and thyroid function tests is assessed after 6-8 weeks of therapy. The daily dose can be increased by 50 µg every 4-6 weeks until clinical and biochemical euthyroidism is achieved. Alternatively, the initial dose may be maintained for 3-4 months, then increased by 25 µg every 4-6 month. The goal of the treatment is to normalize serum TSH, which may require up to 6 months. A thyrotoxic range for serum TSH should be avoided. In this condition, free T4 is usually normal, but often in the high normal range, while free T3 is normal. Once a constant dose of T4 has been reached, thyroid function should be evaluated every 9-12 months unless interference with drugs (anti-epileptic drugs, rifampin, amiodarone) or an event such as pregnancy occurs. The main difficulty with T4 treatment may be the compliance of the patient. Treatment is usually a definitive one. Despite a few examples, mainly from Japan, of reversal of hypothyroidism either with the prevention of excess iodine intake or because of the disappearance of blocking anti-TSH receptor antibodies, systematic regular testing of restoration of thyroid function is not cost-effective and should not be recommended. In hypothyroidism of rapid onset, such as in iatrogenic hypothyroidism, substitution treatment should be rapidly instituted with full initial dosage. In patients with ischemic heart disease, initiation of treatment requires special attention. It may be necessary to start with a very small dose, such as 25 µg on alternate days, and a slow increasing program. It may not be possibile to achieve full replacement therapy in some patients with coronary artery disease so that concomitant coronary revascularization may be necessary. In the elderly patient, the replacement dose of L-T4 is somewhat lower - by 10 % approximately - than in younger adults because daily production rates of T4 and T3 are reduced with advanced age. Also, the cardiac risk of initiation of treatment should be considered. During pregnancy, thyroid economy is modifided in that L-T4 needs are increased by 50-100 µg per day or approximately doubled. In view of the likely importance for early brain development of maternal-to-fetus T4 transfer during the first weeks of pregnancy, the dose of L-T4 should be adjusted without delay aiming at an upper normal free T4 level. TSH should be maintained well within the normal range. The same rule should apply throughout pregnancy since significant transfer of maternal T4 to fetus has also be demonstrated in late pregnancy. It should be mentioned that if, because of the presence of a goiter at ultrasonography, fetal hypothyroidism is considered, biological thyroid workup may be performed on blood sampled through cordocentesis with a 1 % morbidity. Once confirmed, fetal hypothyroidism may be treated with intra-amniotic L-T4 injections, 250-500 µg per week for 2 to 4 weeks. In neonatal hypothyroidism, L-T4 replacement therapy should be prompt and adequate so that serum T4 is normalized with a delay less than 3 weeks. The rule is to maintain serum T4 in the upper half of the normal range. Initial L-T4 dosage is 10-15 µg/kg/day for 6 months, then adjusted at 4-6 week intervals for 6 months and every 2-3 months thereafter. Serum TSH concentrations may remain elevated although values less than 20 mU/l are usual when T4 levels are high normal. However, iatrogenic thyrotoxicosis should be avoided. Treatment promptness and adequacy insure normal intellectual developement. |
