RAI-Associated Thyroid Antibodies Link to Neonatal Hyperthyroidism

Nancy A Melville

October 25, 2017

VICTORIA, British Columbia — Elevated maternal thyroid-stimulating hormone (TSH) receptor antibody (TRAb) levels linked to previous radioiodine (RAI) treatment for Graves' disease are associated with an increased risk of neonatal hyperthyroidism, new research shows.

"The findings show that fetuses of pregnant Graves' disease patients whose TRAb value is 9.7 IU/L or higher in the third trimester should be carefully followed up by an obstetrician during pregnancy, and the newborns should be carefully followed up by a pediatrician after birth," first author Ai Yoshihara, MD, PhD, of Ito Hospital, in Tokyo, Japan, told Medscape Medical News.

The findings were presented here at the 2017 Annual Meeting of the American Thyroid Association.

Graves' disease patients who are treated with RAI therapy have been shown to have increased levels of TRAb for years after the therapy, with one study showing significantly higher levels over 5 years' post–radioiodine therapy, as well as a significantly lower chance of becoming TRAb-negative, compared with patients treated with antithyroid medication or surgery (Eur J Endocrinol 2008;158:69-75).

Little is known, however, about the effect of those higher TRAb levels on infants born to mothers who conceive after RAI therapy, and this research represents the first time the incidence of neonatal hyperthyroidism has been documented in this group of patients.

These new findings should therefore serve as a flag to endocrinologists to follow carefully all women who have a history of Graves' disease and who subsequently become pregnant and to communicate the risks of neonatal hyperthyroidism among these women to obstetricians and pediatricians, said one commentator.

The Longer After RAI Therapy, the Lesser the Risk of Neonatal Hyperthyroidism

To evaluate the effects, Dr Yoshihara and colleagues retrospectively investigated the incidence of neonatal hyperthyroidism among newborns of 145 mothers with Graves' disease who were born within 2 years of the mothers' treatment with radioiodine therapy.

Neonatal hyperthyroidism was diagnosed based on clinical symptoms as well as TSH and free-thyroxine levels in cord blood samples or in a blood sample collected from the neonates within the first week of birth.

The median age of the mothers at the time of RAI therapy was 28 years, and the mean thyroid volume was 48.8 mL (range, 13.1–203.8).

Among the 145 births, seven (4.8%) newborns developed neonatal hyperthyroidism.

Mothers of newborns with neonatal hyperthyroidism, compared with those without, had higher median TRAb levels when they received the RAI therapy (40 vs 10.25; P = .019) and higher TRAb in the first trimester (40 vs 6.5, respectively; < .0001) and in the third trimester (22.4 vs 2.4; < .0001).

Other characteristics associated with neonatal hyperthyroidism included younger age at the time of RAI therapy (= .026) and younger age at delivery (= .021). There were no differences between the groups in terms of thyroid volume when RAI treatment was given and radioiodine dose.

A receiver operating characteristic (ROC) curb analysis further showed TRAb value in the third trimester to represent the only significant risk factor for neonatal hyperthyroidism, with a cutoff TRAb level in the third trimester of 9.7 IU/L predicting neonatal hypothyroidism, with a sensitivity of 100%, specificity of 87.7%, and area under the curve (AUC) of 0.94.

Among the 23 newborns of mothers who had TRAb levels above 9.7 IU/L in the final trimester, seven (about 30%) exhibited neonatal hyperthyroidism.

The incidence of neonatal hyperthyroidism was 5.9% (two of 34) of infants born when conception was within 6 to 12 months after RAI therapy; 5.5% (three of 55) when conception was within 12 to 18 months of RAI therapy; and 3.6% (two of 56) when it occurred 18 to 24 months after the therapy.

Important, Novel Insights Into Risks of RAI Therapy for Offspring

Dr Yoshihara noted that the findings provide important, novel insights on the risks of RAI treatment to offspring.

"Neonatal hyperthyroidism is rare in the general population," she said. "The incidence of neonatal hyperthyroidism among the newborns born to mothers with Graves' disease who conceived after radioiodine therapy has not been reported in the past."

In commenting on the study, Jorge H Mestman, MD, a clinical professor of medicine at the University of Southern California Keck School of Medicine in Los Angeles and comoderator of the session, said the findings should serve as an important message of caution for clinicians.

"This is a [message] to all endocrinologists to follow mothers, even those who are euthyroid, who have a history of Graves' disease, because if we don't call the obstetrician, the diagnosis of neonatal hyperthyroidism could be missed, which could be tragic."

The authors and Dr Mestman had no relevant financial relationships.

2017 Annual Meeting of the American Thyroid Association. October 19, 2017; Vancouver, British Columbia. Abstract 11.

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