Abstract
We thank the authors for their interest in our work. We very much agree with the fact that careful monitoring of the maternal thyroid status, and regulation of the medication dose accordingly, should prevent cases of overtreatment of pregnant women with antithyroid drugs.
Recently, we systematically reviewed cases of antithyroid drug-induced fetal goiter and the course of treatment in such cases (1). Two cases of fetal death were seen in connection with maternal antithyroid drug dose adjustment alone (2,3), compared with none in the cases of intra-amniotic levothyroxine treatment. Regarding the “prompt reaction” of dose adjustment referred to by the authors, the effect of adjusting maternal antithyroid drug dose were seen after several weeks (4,5) compared with days (6 –9) with intra-amniotic levothyroxine treatment. Invasive treatment thus minimizes the time of fetal hypothyroidism, polyhydramnios, and accordingly, the risks connected to both.
Regarding (i): In our opinion, fetal diagnostics are particularly important in women with Graves disease being treated with antithyroid drugs. In such cases, fetal thyroid dysfunction can be caused by two opposites: placental passage of thyrotropin receptor stimulatory antibodies (leading to fetal hyperthyroidism) or placental passage of antithyroid drugs given to the mother (leading to fetal hypothyroidism). Either case poses a risk to the fetus, and the proper course of treatment is critical. Regarding (ii): Ultrasound diagnostics of a fetal goiter are not always reliable (1,5,6,10,11). We believe that the benefits of securing the proper treatment by invasive diagnostics outweighs the risks [0.3% increased risk of abortion by midtrimester amniocentesis (12)] compared with the risks of reducing antithyroid medication in cases wherein the fetus is in fact thyrotoxic (13,14).
Regarding (iii): The purpose of intra-amniotic levothyroxine treatment is not only to reverse polyhydramnios but also to render the fetus euthyroid. Increasing amount of research underlines the damage of fetal hypothyroidism to the neurological development (15 –17). In our reported cases, both the mother and the fetus had a low free thyroxine level because of overtreatment with antithyroid drugs. Thus, unlike other cases of congenital hypothyroidism, placental transfer of maternal thyroid hormone did not protect the fetal brain development.
Hopefully, we will never see a sufficient amount of cases to obtain scientific evidence of either course of treatment. Each case of antithyroid drug-induced fetal goiter remains to be evaluated (preferably, prevented) by endocrinologists, obstetricians, and experts in fetal medicine. Centralization of care of pregnant women treated for thyroid dysfunction is therefore most warranted. Nevertheless, our review (1) of cases of antithyroid drug-induced fetal goiter speaks in favor of invasive treatment—one might do more harm by abstaining from this effective treatment. In the words of Gharib et al.: “lack of definitive evidence for a benefit does not equate to evidence for lack of benefit” (18).