ually 120 – 175 mg/m2 body surface area daily divided into three equal doses every eight hours. Methimazole can be used in place of PTU; approximately one-tenth as much, in milligrams, is required.
Methimazole is now the preferred drug. During therapy the dosage can usually be gradually reduced. Many patients will be satisfactorily controlled by once-a-day treatment. Although the plasma half-life of methimazole in children is only 3-6 hours, the drug is concentrated in the thyroid and maintains higher levels there for up to 24 hours after a dose [215.1]. The program is similar to that employed in adult thyrotoxicosis. It is sensible to see the child once each month, and at that time to make sure that the program is being followed and progress made. Any evidence of depression of the bone marrow should prompt a change to an alternative drug or a different form of treatment, as discussed below. At the end of one or two years the medication is withdrawn. If thyrotoxicosis recurs, a second course of treatment lasting for one year or more may be given. A decrease in the size of the goiter during therapy is good evidence that a remission has been achieved. Progressive enlargement of the gland during therapy implies that hypothyroidism has been produced. This enlargement can be controlled by reduction in the dose of antithyroid drug or by administration of replacement thyroid hormone. There is no adequate rule for deciding when medical therapy has failed. After courses of antithyroid drug therapy totaling two to four years and attainment of age 15, if the patient still has not entered a permanent remission it is probably best to proceed with surgical or 131-I treatment. Barrio et al (215.1) reported on truly long term antithyroid drug therapy, which achieved 40% remissions in pediatric patients, with average time to remission of 5.4 years. Non-remitters were cured by RAI or surgery. Leger reported a similar program with 50% of children appearing to enter a permanent remission (215.12). Occasionally a drug reaction develops while the condition is being controlled with an antithyroid drug. A change to another thiocarbamide may be satisfactory, but patients should be followed carefully. If a reaction is seen again, or if severe neutropenia occurs, it is usually best to stop antithyroid drug therapy and (1) give potassium iodide and an agent such as propranolol and to proceed with surgery, or (2) to give 131-I. RAI therapy will be necessary if surgery is contraindicated by uncontrollable thyrotoxicosis,for whatever reason, or with prior thyroidectomy. Thyrotoxicosis in children has been recently reviewed(215.2)
Approximate daily dose of MMI (mg)
Intrauterine and Neonatal Thyrotoxicosis
Thyrotoxicosis in utero is a rare but recognized syndrome occurring in pregnant women with very high TSH-R stimulating Ab in serum, due to transplacental passage of antibodies. It can also develop in the neonate. It is possible to screen for this risk by assaying TSAb in serum of pregnant women with known current or prior Graves’ Disease. Intra-uterine thyrotoxicosis causes fetal tachycardia, failure to grow, acceleration of bone age, premature closure of sutures, and occasionally fetal death. Multiple sequential pregnancies with this problem have been recorded. Clinical diagnosis is obviously inexact. Antithyroid drugs can be given, but control of the dosage is uncertain . Propylthiouracil is considered to be the safest drug to use in the first trimester, because of fetal anomalies attributed to methimazole exposure in early pregnancy( 217.1), with switching to MMI in the second and third trimesters..
Luton et al (217.2) recently provided their extensive experience in managing these difficult cases. Measurement of TSAb is important. Mothers with negative TSAb assay, and not on ATD, rarely have any fetal problem. Mothers with positive TSAb or on ATD must be monitored by following maternal hormone and TSH levels, fetal growth , heart rate, and by ultrasound for evidence of goiter or other signs of fetal hyper- or hypothyroidism. If maternal hormone lev