Different fetal-neonatal outcomes in siblings born to a mother with Graves-Basedow disease after total thyroidectomy: a case series

The first pregnancy occurred six years after the total thyroidectomy and four years after the radioiodine therapy. The mother was on substitutive therapy with L-thyroxine (225 μg/day). TRAb levels were not detected during the pregnancy. A Cesarean section was performed at 34 weeks of gestational age (GA), because of intrauterine death of a male fetus. An autopsy was not performed.

A year later, the woman became pregnant again. She was still on substitutive therapy with L-thyroxine (225 μg/day) and her hormone levels were within the normal range throughout the whole length of pregnancy. Fetal echocardiographic evaluation was performed one day before the delivery. The report was consistent with mild cardiomegaly and slight sinusal tachycardia, with a fetal heart rate (HR) of 160-170 bpm. TRAb were checked by an enzyme-linked immunosorbent assay (ELISA) with the suspicion of fetal hyperthyroidism. The levels were 32 U/l (normal value [n.v.] <12 U/l). Fetal thyroid ultrasonography was reported to be normal. The following day, the echocardiographic evaluation showed incipient fetal heart failure, severe tricuspid insufficiency, moderate sinusal tachycardia and low amniotic fluid. A Caesarean section was performed at 31 weeks of GA. A female baby was born with an Apgar score of 8-9 and a birth weight of 1870 g. She was transferred to the neonatal intensive care unit. On her 1st day of life (DOL), TRAb were 24 U/l (n.v. <12 U/l). Thyroid hormones and TSH levels (Figure 1) were consistent with neonatal hyperthyroidism (fT3 19.9 pg/ml (n.v. 2.3-4.2), fT4 >75 pg/ml (n.v. 8.5-15.5), TSH 0.03 UI/ml (n.v. 0.35-8)). The baby developed the following clinical signs of hyperthyroidism: considerable weight loss (-12% compared with birth weight), inconsolable crying, irritability and tachycardia at rest (HR 180-190 bpm). Echocardiogram was normal and was not in agreement with prenatal data. Thyroid ultrasonography results were within the normal range. Both clinical signs and thyroid hormone levels normalized during hospitalization and therapy was not required. The baby was discharged on the 36^th DOL. TRAb levels were 2 U/l (n.v. <1.5 U/l).

The third pregnancy occurred nine years after total thyroidectomy and seven years after radioiodine therapy. The mother was receiving substitutive therapy with L-thyroxine (225 μg/day). Hormone and TSH levels were within the normal range throughout the whole pregnancy. Lugol's solution (potassium iodine) at the dosage of 8 mg/day was administered to the mother, starting in the 25th week of GA and continuing for 20 days, because of fetal tachycardia. From the 31st week until delivery, methimazole (20 mg/day) was added because of persistent fetal tachycardia. Lugol's solution (8 mg/day) was added during the last two weeks. TRAb levels, checked with a radio immunosorbent test (RIA), were about 400 UI/l at 19 and 29 weeks of GA, respectively (n.v. <10 UI/l). Fetal thyroid ultrasonography and echocardiography were normal. At 33 weeks of GA, a female baby was born by Caesarean section, which was carried out due to the persistent fetal tachycardia. The birth weight was 2200 g and the Apgar score was 8-9. Echocardiographic evaluation at birth showed a patent ductus arteriosus with initial overload of left cardiac sections and slight tricuspid insufficiency. All these findings disappeared on the 6th DOL. HR was 160-180 bpm. Thyroid hormones levels were within the normal range and TRAb levels were 35 U/l (n.v. <12 U/l).

A considerable weight loss was detected (-10.5% compared with birth weight).

By the 7th DOL, the baby was extremely irritable with inconsolable crying. At that point, thyroid hormones and TSH levels (Figure 2) were consistent with hyperthyroidism (fT3 5.4 pg/ml (n.v. 2.3-4.2), fT4 34.7 pg/ml (n.v. 8.5-15.5), TSH 0.03 UI/ml (n.v. 0.35-8)), probably due to maternal antithyroid drug clearance. Lugol's solution was started (8 mg/3 times a day). On the 9th DOL, the newborn presented supraventricular parossistic tachycardia (HR 330 bpm). Diving reflex was necessary to reduce HR to 180 bpm. The dosage of Lugol's solution was increased to 24 mg/3 times a day and oral administration of diazepam was necessary, because of a persistent clinical pattern of hyperthyroidism (tachycardia, supraventricular extrasystoles, hyperexcitability, irritability, inconsolable crying and vomiting). On the 13th DOL, propranolol was started (1 mg/kg/day, in 4 daily doses), due to persistent tachycardia. It was withdrawn on the 28th DOL. The baby was discharged at one month old and discontinued Lugol's solution after a week. TRAb levels were not dosable at that point. Thyroid hormones levels were normal (fT3 3.3 pg/ml (n.v. 2.3-4.2), fT4 11 pg/ml (n.v. 8.5-15.5)) at two months of life. Thyroid ultrasonography consistently showed normal results.