Fetal goiter identified in a pregnant woman with triiodothyronine-predominant graves’ disease: a case report

The patient became pregnant naturally, at a time when her thyroid function was not satisfactorily controlled by a high dose of propylthiouracil (PTU). An alternative treatment (isotope therapy or surgery) was being considered. Because of hyperemesis gravidarum, oral medications were no longer an option, resulting in her thyroid function deteriorating during week 13 of her pregnancy. Her TRAb level was 43.6 IU/L at that time, and a daily dose of 50 mg potassium iodide (KI) was administered. As a result, her thyroid function was under control, and KI administration was discontinued at week 17. The patient’s FT3 level fluctuated between normal and elevated, whereas her FT4 and TSH levels were low. Her TRAb level gradually declined but was still high at week 33 (18.4 IU/L).

At 33 weeks and 5 days of gestation, the amniotic pocket and the cervical lengths were 8.1 and 2.6 cm, respectively, indicating worsening hydramnios and threatened premature labor. A blood test showed that the patient’s TSH level had increased to within the normal range. Because pre-pregnancy reduction in her antithyroid medication caused sudden worsening of her thyroid function, she was prescribed a daily supplementary course of 25 μg levothyroxine. At 34 weeks of gestation, she was admitted for hydramnios management and prevention of threatened premature labor.

On admission, blood sampling showed an increased TSH level; thus, her thyroid function had improved. Because she was experiencing frequent uterine contractions, we consulted the Department of Diabetes and Endocrinology at our hospital and initiated a continuous drip of ritodrine hydrochloride under careful monitoring for aggravation of hyperthyroidism. At 34 weeks and 4 days of gestation, a transabdominal ultrasound indicated enlargement of the fetal thyroid. It showed a transverse diameter and circumference of 58.4 and 178 mm, respectively (mean values at the 35th week of pregnancy: 18.9 mm and 51.1 mm respectively [8]) (Fig. 1a). The blood flow was diffusely increased (Fig. 1b), and hydramnios was observed. In addition, the epiphyseal nucleus of the distal femur could not be confirmed. The fetus was in face presentation (Fig. 2a). We assumed that the cause of the hydramnios was the inability to swallow the amniotic fluid due to the size of the thyroid. We suspected that the PTU had crossed the placenta and migrated to the fetus, causing fetal goiter; therefore, we initiated a reduced dose of antithyroid medication for the mother at 34 weeks and 5 days of gestation. After reducing the PTU dose from 200 to 100 mg/day, neither the mother nor the fetus showed signs of hyperthyroidism. The dose of PTU was gradually reduced to 50 mg/day, while the levothyroxine dose was increased to 100 μg/day. The fetal thyroid showed a shrinking tendency, as magnetic resonance imaging (MRI) performed at 36 weeks and 3 days of gestation showed a 3-cm fetal thyroid transverse diameter (transverse section; Fig. 2b). The next day, an ultrasound indicated that the AFI had decreased from 24 to 15 cm, and that the fetus’ thyroid blood flow had returned to normal (restricted to the thyroid margins). The fetus had moved into a normal flexion position.

Because of the goiter, we were unable to confirm that there would be a patent airway after delivery. Therefore, we speculated that a tracheotomy would be necessary. After consultation with both the Department of Neonatal Medicine and the Department of Pediatric Surgery, an elective cesarean delivery was performed at 36 weeks and 5 days of gestation. On day 7 after delivery, the mother showed signs of hyperthyroidism, which necessitated an increase in her PTU dose.

A diagram describing the therapeutic course from pre-pregnancy to postpartum is shown in Fig. 3.

The infant was a male, weighing 2817 g, with Apgar scores of 8 and 9 at 1 and 5 min, respectively. His umbilical aortic blood pH was 7.26. The anterior cervical region had a transverse diameter of 40 mm, indicating an enlarged thyroid gland (Fig. 4). Crying was normal, and no resuscitation was necessary. The infant was admitted to the neonatal intensive care unit (NICU) immediately after birth because of premature delivery and goiter. No bradycardia was observed, and other than the goiter, no external deformities that would suggest congenital hypothyroidism, such as megaloglossia or umbilical hernia, were observed.

A sonography indicated that the thyroid gland had a left-to-right transverse diameter of 41.4 mm (normal range [mean ± 2SD]: 13.9 ± 4.0 mm [9]) and an isthmus of 5.2 mm, indicating enlargement. An ultrasound showed no increased blood flow. Radiographs indicated no epiphyseal nucleus of the distal femur, which showed that fetal bone maturation was delayed because of the fetal hypothyroidism.

Thyroid function tests were conducted using the umbilical blood at delivery, and the results were as follows: FT3, 1.7 pg/mL (normal range [mean ± SD]: 1.70 ± 0.034 pg/ml); FT4, 1.6 ng/dL (normal: 1.17 ± 0.14 ng/dl); and TSH, 25.18 μIU/mL (normal: 10.27 ± 6.31 μIU/mL) [10]. The TRAb level was 17.4 IU/L. No treatment was given until 5 days of age, when thyroid function tests indicated a tendency toward hyperthyroidism, (FT3 = 3.5 pg/mL, FT4 = 2.7 ng/dL, and TSH = 2.56 μIU/mL). The infant was administered a course of thiamazole (MMI) (0.5 mg/kg/day). No major changes in the size of the infant’s thyroid gland were observed during the hospital stay. Because of neonatal jaundice, the infant was treated with 24-h phototherapy starting at 4 days of age. His progress was stable, and he was discharged at 18 days of age, weighing 3.1 kg. Following discharge, the MMI dose was gradually decreased as TRAb levels dropped, and it was discontinued at 51 days of age. At 10 months of age, the infant’s thyroid function was normal, despite persistent goiter. There was no evidence of any developmental delays. Currently, the infant is under the continuous care of the Department of Pediatrics.