Endocrine Abstracts

JOINT2467

Introduction: Graves disease is an autoimmune endocrinopathy caused by thyroid-stimulating hormone receptor antibodies (TSH-R-Ab). Classically, this results in hyperthyroidism as thyroid-stimulating autoantibodies (TSAb) predominate. Nevertheless, these antibodies can also exhibit blocking (TBAb) or neutral activity. The net activity determines the clinical presentation and approach. Specific consideration and monitoring in pregnancy is suggested due to TSH-R-Ab’s ability to migrate transplacentally and affect the fetus’ thyroid gland. However, conventional thyroid receptor binding tests detect all types of thyroid hormone receptor antibodies without differentiating between them.

Case Report: A 36-year-old woman with Graves disease without ocular involvement had been treated for 56-months with propylthiouracil (PTU) and L-T4 replacement therapy. The TSH-R-Ab titer, measured with two different chemiluminescence immuno-assays during follow-up, remained persistently elevated. During the first trimester of her twin pregnancy, we noticed a tendency toward hypothyroidism and a remarkably increased TSH-R-Ab titer, considering the difference in immunoassay. The quantity and functional properties of TSH-R-Ab can be altered during gestation due to immunological changes. In classical Graves caused by TSAb, these antibodies will usually decrease during pregnancy. However, the antibodies may become blocking or neutral in rare cases. In consideration of hypothyroidism, the dose of PTU was reduced incrementally. L-T4 was associated given the low-to-normal T4-titer, where we aimed for higher values to sustain neurological fetal development. Ultimately, PTU was stopped and L-T4 progressively increased according to thyroid testing every two weeks. Development of both fetuses was normal with no evidence of hypo- or hyperthyroidism. Considering the appearance of TBAb would imply a risk of hypothyroidism in the fetuses, a functional TSH-receptor-antibody assay was requested to differentiate between all types of TSH-R-Ab. This test was performed by Prof. Dr. Kahaly at Johannes Gutenberg University. We concluded that neither thyroid-stimulating nor thyroid-blocking antibodies were present. Therefore, the measured antibodies were neutral. A favorable result given that these antibodies do not affect thyroid function, neither the mother’s nor the fetuses’.

Conclusion: When observing a switch between hyper- and hypothyroidism in patients with known Graves disease, it is important to screen for functional TSH-R-Abs. This distinction is important during pregnancy because inadequate maternal L-T4 levels could irreversibly impair fetal neurological development. Other indications for screening could include Graves disease with positive TSH-R-Abs persisting after 18 months of block-replacement therapy, before pregnancy when there is a known history of auto-immune thyroid disease addressed with thyroidectomy or radioactive iodine and autoimmune thyroid dysfunction secondary to immune reconstitution therapy.