Evaluation and management of neonatal Graves' disease
- Stephen LaFranchi, MD
Stephen LaFranchi, MD
- Professor of Pediatrics
- Oregon Health & Sciences University
Neonatal Graves' disease refers to the hyperthyroidism that is seen in a small percentage of infants born to mothers with Graves' disease. Although neonatal Graves' disease is usually self-limited, it can be severe, even life-threatening, and have deleterious effects on neural development. Maternal Graves' disease is by far the most common cause of neonatal hyperthyroidism. Active Graves' disease in a pregnant woman can lead to either hyper- or hypothyroidism in the fetus and neonate, depending on the balance of the maternal stimulatory and inhibitory antibody and antithyroid drug effect . Babies destined to develop neonatal Graves' disease, however, are almost always hyperthyroid at or within one week of birth. (See "Hyperthyroidism during pregnancy: Treatment".)
Graves' hyperthyroidism occurs in approximately 0.2 percent of women, and it occurs in approximately one to five percent of infants born to these mothers [2-4]. Thus, neonatal Graves' hyperthyroidism would be expected to occur in approximately 1:25,000 neonates and affects males and females equally.
Why only 1 to 5 percent of infants of mothers with Graves' hyperthyroidism are affected is explained by the level of the maternal serum stimulatory thyrotropin receptor antibody (TSHR-Ab). The higher the maternal stimulatory TSHR-Ab concentration is during the third trimester, the greater is the likelihood of neonatal Graves' hyperthyroidism. In practice, neonatal hyperthyroidism is most likely when the TSHR-Ab activity of maternal serum is above 500 percent of the values in serum of normal subjects [5,6]. This was illustrated in a study of 29 pregnant women with a history of Graves' disease that confirmed the relationship of high TSHR-Ab and neonatal thyrotoxicosis. In the 35 live births, there were six cases of neonatal Graves' disease, all of whom had a TSHR-Ab level above 500 percent of normal; in addition, six other babies with a TSHR-Ab above 500 percent of normal did not develop hyperthyroidism. In this study, measurement of the TSHR-Ab had a 100 percent sensitivity, with 50 percent specificity. The incidence of neonatal Graves' disease in this study was 17 percent, which is a higher rate than previously reported .
Neonatal (and fetal) Graves' hyperthyroidism results from the transplacental passage of maternal stimulatory thyrotropin receptor antibody (TSHR-Ab) [3,8,9]. Most neonatal Graves' disease occurs in the setting of active Graves' hyperthyroidism in the mother. However, the disorder also can occur in infants of women with a history of Graves' hyperthyroidism treated with thyroidectomy or radioactive iodine in the past . After a woman with Graves' disease undergoes one of these treatments, the risk of having an infant affected by neonatal Graves' disease falls over time, in conjunction with decreases in TSHR-Ab levels. The risk of neonatal Graves' disease is low five years after radioactive iodine, but some mothers still have persistent TSHR-Ab elevation and will deliver babies with neonatal Graves' disease . A study of the time course of decrease in TSHR-Ab after total thyroidectomy reported that the median TSHR-Ab half-life was 93.5 days, though it was longer in patients with Graves' ophthalmopathy and/or those who smoked (162.5 days for one of these risk factors and 357.4 days for those with both) . As described above, measurement of maternal serum TSHR-Ab may be helpful in predicting whether a newborn will be affected. (See "Hyperthyroidism during pregnancy: Treatment".)
Serial in utero ultrasonography with measurement of fetal thyroid size has also been reported to help determine which neonates are likely to manifest neonatal hyperthyroidism . In a report of 20 pregnant women with Graves' disease treated with an antithyroid drug, the fetal thyroid gland was enlarged in five pregnancies. In these five patients, the maternal antithyroid medication dose was decreased resulting in a reduction of the fetal thyroid gland to a normal size in three cases but in the other two cases the gland remained enlarged. These latter two infants both developed neonatal Graves' disease . Thus, care must be taken because fetal goiter may be a feature of in utero hypothyroidism or hyperthyroidism. Another study using ultrasonography reported that a hyperthyroid fetus was more likely to have a goiter with central vascularization, along with other findings, including fetal tachycardia, increased fetal movement, and advanced bone maturity .
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- Natural history
- Other causes of neonatal hyperthyroidism
- - Thyrotropin-receptor activating mutations
- - Alpha subunit G protein-activating mutation (McCune-Albright syndrome)
- CLINICAL MANIFESTATIONS
- Timing of symptoms
- Maternal Graves' disease during pregnancy
- - Prenatal testing
- - Cord blood
- - Testing of the neonate
- Infants coming to attention after birth
- Neonatal Graves’ disease
- Hypothyroidism (transient)
- FETAL HYPERTHYROIDISM
- SUMMARY AND RECOMMENDATIONS