Fetal Thyroid Gland Monitoring in Graves’ Disease During Pregnancy

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Pregnant women with Graves’ disease are at high risk of fetal death or permanent neurological impairment of their children. Luton et al investigated a new approach to the fetal diagnosis of thyroid dysfunction by use of fetal thyroid ultrasonography in pregnant women with active or treated Graves’ disease. Luton’s group presented a prospective study monitoring 72 mothers with past or present Graves’ disease and their fetuses from 22 weeks’ gestation (WG) (Figure). Fetal thyroid size was assessed according to Ranzini et al,¹ thyroid Doppler signals and bone maturation were evaluated by ultrasonography. Thyroid function was measured at birth in the neonates. In the mother, thyroid function and TSH receptor antibodies were measured monthly. When the data did not document fetal hyperthyroidism or hypothyroidism, fetal blood sampling was performed (with maternal consent). Once the type of fetal dysfunction was determined, maternal treatment was adjusted. When fetal blood sampling showed fetal hypothyroidism intraamniotic maternal levothyroxin (L-T₄) was administered by amniocentesis, after a careful multidisciplinary decision.

Ultrasonography for fetal thyroid monitoring according to maternal status and cord blood thyroid function test results.
(1) In one mother, FT₄ (20.2 pmol/liter) was at the upper limit of normal with suppressed TSH (<0.05 mIU/liter) despite the high maternal dose of propylthiouracil (PTU).
(2) FT₄, Mean of FT₄ in all of these newborns with 1 SD ; TSH, mean TSH in all of these newborns with 1 SD.

Adapted from Luton D, et al. J Clin Endocrinol Metab. 2006;90:6093–6098.

In the low-risk group (mothers were negative for TSH-receptor antibodies [n = 31] and the fetus did not receive thyroid medication) the fetuses had normal test results and no evidence of prenatal goiter. Whereas, in the high-risk group (mothers treated with antithyroid drugs [n = 41]) 11 fetuses had evidence of goiter at 32 WG. These were found to be either hypothyroid (n = 7) or hyperthyroid (n = 4). Fetal thyroid dysfunction was treated by adjusting the mother’s therapy and /or by intraamniotic treatment. There was one death in a late referral, and 10 favorable outcomes with normal or slightly altered thyroid function in the neonates. This paper focuses on the contribution of fetal thyroid ultrasonography at 32 WG for screening of clinically relevant fetal thyroid dysfunction leading to treatment. The sensitivity and specificity of this technique was 92% and 100%, respectively. Interestingly, in 10 out of 11 cases with fetal thyroid dysfunction the mother had no history of thyroidectomy.

In conclusion, ultrasonography of the fetal thyroid gland, performed by an experienced person is an excellent diagnostic tool. It adds to the current criteria for evaluating the mother’s Graves’ disease and the fetal thyroid status. It requires a close collaboration of pediatrician, adult endocrinologist, and obstetrician, and an appropriately trained ultrasonographist.

Luton D, Le Gac I, Vuillard E, et al. Management of Graves’ disease during pregnancy: the key role of fetal thyroid gland monitoring. J Clin Endocrinol Metab. 2006;90:6093–6098.

Editor’s Comment

This is a remarkable prospective follow-up of mothers with Graves’ disease and their fetuses. The evaluation of the fetal thyroid status by the addition of fetal thyroid ultrasound monitoring was based on well-described and validated criteria. The first goal was achieved by showing that the fetal ultrasonography can be a reliable non-invasive tool, if performed by a well-trained ultrasonographist working with a prenatal standardized technique. The authors used the conventional approach combining maternal criteria (TSH receptor antibody titer, and monitoring of antithyroid treatment) and fetal criteria (fetal heart rate, bone maturation and thyroid Doppler signal). These criteria proved effective in differentiating hypothyroidism and hyperthyroidism in all fetuses with goiter. This report deserves confirmation by other groups. In the meantime we may follow their proposal that, during pregnancy in women who are receiving antithyroid drug treatment and/or have positive tests for TSH receptor antibodies, fetal thyroid ultrasonography should be performed monthly after 20 WG to screen for goiter. It should be stressed that for the sake of this study fetal blood was sampled from 6 of the 11 fetuses with goiter and the results consistently confirmed the suspected diagnosis. It is therefore proposed that fetal blood sampling be reserved for those cases in which intraamniotic T₄ injection is considered or for cases in which the fetal status is in doubt, provided that the fetus is at high risk.

Raphaël Rappaport, MD

Reference - (linked to )

Ranzini AC, Ananth CV, Smulian JC, Kung M, Limbachia A, Vintzileos AM. Ultrasonography of the fetal thyroid: nomograms based on biparietal diameter and gestational age. J Ultrasound Med. 2001; 20:613–617.

Last Updated: 04/30/2008