ps 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 levels are low and TSH elevated, with fetal goiter and evidence of hypothyroidism, ATD therapy is reduced and intra-amniotic T4 may be given. If maternal T4 levels high and TSH low, with fetal goiter and signs of fetal hyperthyroidism, increased doses of ATD are suggested. If the probable metabolic status of the fetus is not clear, fetal blood sampling is feasible although carrying significant risk to the fetus. Plasmapheresis to reduce maternal TRAb has been recommended, but few facts are available. Thyrotoxicosis is rare in the newborn infant and is usually associated with past or present maternal hyperthyroidism. 
Neonatal hypermetabolism usually arises from transplacental passage of TSAb. Frequently the infant is not recognized as thyrotoxic at birth, but develops symptoms of restlessness, tachycardia, poor feeding, occasionally excessive hunger, excessive weight loss, and possibly fever and diarrhea a few days after birth. The fetus converts T4 to T3 poorly in utero, but switches to normal T4 to T3 deiodination at birth. This phenomenon may normally provide a measure of protection in utero that is lost at birth, allowing the development of thyrotoxicosis in a few days.
The syndrome may persist for two to five weeks, until the effects of the maternal antibodies have disappeared. The patient may be treated with propranolol, antithyroid drugs given according to the schedule above, and iodide. The antithyroid drug can be given parenterally if necessary in saline solution after sterilization by filtration through a Millipore filter. Newborn infants with thyrotoxicosis are frequently extremely ill, and ancillary therapy, including sedation, cooling, fluids in large amounts, electrolyte replacement, and oxygen, are probably as important in management as specific therapy for the thyrotoxicosis. Propranolol is used to control the tachycardia (218.1). Because of the increased metabolism of such infants, attention to fluid balance and adequacy of nutrition are important. The patient usually survives the thyrotoxicosis, an