Sequential Amniotic Fluid Thyroid Hormone Changes Correlate with Goiter Shrinkage following in utero Thyroxine Therapy

Abstract

Several isolated reports of fetal goiter treatment have shown limited generalizability of approaches and provide no real guidance for optimal timing, dosages, and treatment strategies. Graves' disease accounts for >60% of these cases. Maternal treatments of hyperthyroidism include antithyroid medications such as methimazole and more commonly propylthiouracil (PTU). Here, our management of a patient with a fetal thyroid goiter from maternal exposure to PTU diagnosed at 23.6 weeks' gestation and the management of other cases allow us propose a general strategy for treatment. Intrauterine therapy with 200 and then 400 μg of levothyroxine (3 weeks apart) showed an 85% reduction in fetal thyroid goiter volume. We collected amniotic fluid samples at the time of treatments and assayed thyroid hormones and associated antibodies which closely reflected the changes in thyroid goiter mass volume. Our observations suggest a weekly or biweekly therapeutic intervention schedule. Utilizing both goiter size as well as a novel approach in using amniotic fluid hormone levels to monitor therapy efficacy might improve the quality of treatments. Only with a standardized approach and collection of amniotic fluid thyroid panels do we have the opportunity to develop the database required to determine the number and timing of treatments needed.

Graves’ disease complicated by fetal goitrous hypothyroidism treated with intra-amniotic administration of levothyroxine

“…Literature has shown efficacy in reducing goitre size following administration of intra-amniotic LT4 7 19 25. LT4 therapy in utero causes biochemical and structural changes in fetal goitres; however, the exact mechanism is not fully understood 26. Moreover, goitre size may not reliably correlate with fetal TSH levels 19.…”

Prenatal Diagnosis of Fetal Goitrous Hypothyroidism in a Euthyroid Mother: A Management Challenge

“…This method has the advantage of being less hazardous . However, even if amniotic sampling is often used, some authors express doubts on the validity of amniotic thyroid levels for reflecting fetal status . Luton et al described a consensus statement suggesting that an increase in TSH in amniotic fluid of greater than 2.5 multiples of the median was effective for diagnosis but had not been used in recent reports.…”

Graves’ hyperthyroidism in pregnancy: a clinical review

“…The fetal (f) thyroid gland develops between 5 and 6 weeks gestation [ 55 ] and starts secreting thyroxine at 10 weeks of gestation [ 56 ]. Fetal thyroid hormone (fTH) production is limited until 18–20 weeks of gestation when fTSH receptors begin to function [ 57 , 58 ]. fTSH levels will begin to rise until 28 weeks of gestation.…”

“…Fetal goiter can cause fetal, obstetric, and neonatal complications including polyhydramnios secondary to reduced swallowing ability, cervical dystocia, and mechanical obstruction of the fetal airway respectively [ 58 , 66 , 67 ]. Cesarean delivery may be preferred due to high risk of labor dystocia from a deflexed head [ 68 ].…”

“…Known as fetal blood sampling, cordocentesis involves US guided placement of a needle into the fetal circulation usually through direct placement into a free loop of umbilical cord or at the cord insertion site. Alternatively, TH concentrations in the amniotic fluid can be measured [ 58 , 65 ]. While less hazardous, amniotic fluid hormone levels have not been validated as a reliable measure of fetal thyroid function [ 56 ].…”