SUN-320 - Current TSI and TRAB Graves' Assays Demonstrate Poor Agreement in Pregnancy to Inform Need of Fetal Surveillance for Fetal and Newborn Graves' Disease

Endocrinologist and Maternal-Fetal Medicine providers rely heavily on the performance of Graves’ antibody (ab) tests to predict the risk of fetal and newborn Graves’ Disease (Fet/NB GD) in pregnant women with a history of or current GD (hx/curr GD). Severe fetal growth restriction and heart failure may occur in Fet/NB GD and require treatment in-utero and/or after delivery. The ATA recommends pregnant patients with hx/curr GD to receive ab testing early and if ≥3X upper-limit-of-normal (ULN) at 18-20 wks, extensive fetal surveillance including serial ultrasounds every 4 wks and non-stress tests (NSTs) be performed. However, newer GD ab assays have replaced older assays which were previously validated as predictors of Fet/NB GD, and the agreement of currently used assays is unstudied. The TRAB Roche assay is a competitive assay measuring both stimulating and inhibitory abs. The Siemens bridge TSI is an automated functional assay targeted to measure only stimulating activity to replace older cell-based assays.
This is a retrospective study of 262 pregnant patients, 18-45 yrs, with hx/curr GD who delivered 1/2021-6/2025 at University Hospital, CO. TSI (Siemen’s Bridge) and TRAB (Roche) assay were drawn within 14 days of one another. McNemar’s test analyzed paired data to determine differential assay elevation propensity. A positive test was defined as ≥3X ULN and a negative test < 3X ULN (1.62 and 5.25 IU/L for TSI and TRAB, respectively).
A total of 361 paired tests were obtained in 262 patients (mean age 31.8 yrs; 21wks); 96% of tests were performed on the same day. Although 78.7% of the pairs were both < 3X ULN, 21.3% had at least 1 positive test (≥3X ULN). Both tests were positive in only 8.3% of pairs. In 12.7% of tests, the TSI was positive and the TRAB negative whereas in only 0.3% of tests, the TRAB was positive when the TSI was negative. Therefore, when the tests were discordant, TSI was the positive test 98% of the time, significantly different than the expected 50% (McNemar test p < 0.001). Conversely, the TRAB was positive only 2% of time when the TSI was negative.
When discordant, the TSI is 40X more likely to be the positive test than TRAB. Clinically important, when the TSI was ≥3X ULN, the TRAB was only positive 40% of the time, potentially resulting in 2-3 times more serial ultrasounds and NSTs than if relying solely on TRAB. This discordance shows the difficulties in directly comparing GD ab assays and the problems using the same 3X ULN to predict risk, as per ATA guidelines. The predictive value of Fet/NB GD using the TSI Siemens assay is unstudied and the Roche assay was based on small numbers and suggested a higher ULN. Until multicenter trials can determine the predictive accuracy of Fet/NB GD using current assays, our data strongly support recalibrating absolute values to a common international standard to establish conversion factors to reduce unneeded costly surveillance and focus on pregnancies at highest risk.