Antibody Screening Urged Before, During Pregnancy for Women With Autoimmune Thyroid Disorder

By Marilynn Larkin

March 25, 2020

NEW YORK (Reuters Health) - Women with a history of autoimmune thyroid disorder should be screened for thyrotropin receptor antibodies (TSH-R-Abs) before and during pregnancy, authors of a case study advise.

"Graves' typically characterized by hyperthyroidism caused by TSH-R-Abs with stimulating properties," Dr. Brigette Decallonne of University Hospitals Leuven in Belgium told Reuters Health by email. "This is particularly important during pregnancy, because these antibodies easily cross the placenta, which can cause fetal hypothyroidism with the risk of impaired neurodevelopment."

In a case report published in Annals of Internal Medicine, Dr. Decallonne and colleagues describe a 28-year-old woman with hyperthyroidism due to typical Graves disease. She had been treated for 36 months with high doses of an antithyroid drug along with L-T4 replacement to avoid hypothyroidism (block-replacement regimen) because of persistently high TSH-R-Ab titers (>40 IU/L; reference value ≤1 IU/L).

Six weeks after both drugs were withdrawn, she developed hypothyroidism. A functional analysis identified TSH-R-Abs with blocking properties, which confirmed a shift from hyperthyroidism to TBAb-induced hypothyroidism. After restarting L-T4 treatment, the woman became clinically euthyroid and maintained that status despite continuously high TSH-R-Ab titers.

Two years later, she became pregnant. During the pregnancy, TSH-R-Abs remained high and blocking, so the L-T4 dose was kept high. Fetal development was normal, and a healthy boy was delivered on term.

In the postpartum period, the newborn developed transient subclinical hypothyroidism that resolved spontaneously during the next three months, along with disappearance of maternal TSH-R-Abs.

The mother's functional TSH-R-Ab status remained unchanged. A second pregnancy followed three years later. The newborn developed a low normal free T4 level and required treatment with L-T4 from postnatal day 18 to day 73. Both children have developed normally.

Dr. Decallonne acknowledged that the team has also experienced less favorable results. "We have faced both neonatal hyperthyroidism in a child born to a hypothyroid mother producing stimulating TSH-R-Abs, as well as neonatal hypothyroidism and severe cognitive impairment in twins born to a hyperthyroid mother with Graves' disease producing blocking TSH-R-Abs," she said.

Dr. David Colombo, Division Chief of Maternal Fetal Medicine at Spectrum Health in Grand Rapids, Michigan, commented by email, "I agree that it would be reasonable to screen for functional TSH-R-Abs prior to pregnancy in high-risk women who have a history of autoimmune disease, radioactive ablation of the thyroid, and thyroidectomy. I believe there will be very few women who have significant findings that will require treatment."

"Currently, we do perform thyroid function testing on women with any autoimmune disease such as diabetes, lupus, etc.," he told Reuters Health. "We used to be more concerned about maternal subclinical hypothyroidism and a potential decrease in subsequent IQ of the child. We found this is not the case. If the patient has a slightly elevated TSH and normal free T4 or a normal TSH and a slightly low free T4, these children do not have any decrease in IQ compared to controls."

"We do follow our pregnant patients with hyper- and hypothyroidism more closely, with frequent ultrasounds and nonstress tests to evaluate for fetal thyroid dysfunction," he said. "We also notify the pediatricians of the maternal disease so that the neonate can be followed closely for transient thyroid dysfunction."

"I would remind clinicians to look for other autoimmune diseases when any single autoimmune disease is present," he concluded.

SOURCE: Annals of Internal Medicine, online March 23, 2020.


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