Endocrine Abstracts

Objective: TSH-receptor antibodies (TRAb) are key markers to distinguish Graves’ disease from gestational hyperthyroidism in pregnancy in clinical practice. We aimed to measure stimulating TRAb (TSI) using the Turbo TSI bioassay for establishment of early pregnancy cut-off and comparison with immunoassay measurements of TRAb.

Methods: We performed a retrospective cohort study within the North Denmark Region Pregnancy Cohort (2011-2015) and identified a random cohort (n = 2,686) as well as a ‘low TSH cohort’ of women with TSH < 0.1 mIU/l in early pregnancy (n = 438). Stored biobank samples were used for TSI measurement with the Turbo TSI bioassay (Quidel/Ortho-Clinical Diagnostics) and compared to previous TRAb measurements with an immunoassay (BRAHMS TRAK Human, Kryptor Compact, Thermofisher Diagnostics Aps). A method- and pregnancy-specific cut-off (95-percentile) for the Turbo TSI bioassay was established among healthy reference individuals in the random cohort (n = 2,299) using Regression on Order Statistics. TRAb- and TSI-status was compared in the ‘low TSH cohort’, and TSH, β-hCG, thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) status were evaluated. Quidel/Ortho-Clinical Diagnostics supported the Turbo TSI bioassay measurements.

Results: The established cut-off for TSI was 0.0418 IU/l for the Turbo TSI bioassay and previously found to be 1.0 IU/l for the TRAb immunoassay. In the ‘low TSH cohort’, 43 women were positive for TSI (9.8%), and 22 women were positive for both TSI and TRAb (group 1). On the other hand, 28 women had discrepant TSI and TRAb results being either positive or negative (group 2), and 388 were negative for both TSI and TRAb (group 3). Median TSH differed by antibody status and was lower in the TSI and TRAb positive group (group 1; 0.004 mIU/l, group 2; 0.020 mIU/l, group 3; 0.038 mIU/l, P = <0.001) as was median β-hCG (group 1; 56 IU/l, group 2; 87 IU/l, group 3; 102 IU/l, P = <0.001), and this group was also more often positive for TPO- and/or Tg-Ab (group 1; 81.8%, group 2; 39.3%, group 3; 7.7%, P = <0.001).

Conclusions: This is the first study to measure TSI in a large cohort of early pregnant women, and a method- and pregnancy-specific cut-off for TSI was established. A high agreement between TSI and TRAb was seen among women with low TSH in early pregnancy, and women positive for TSI and TRAb had more severe hyperthyroidism and biochemical markers compatible with autoimmune thyroid disease rather than gestational hyperthyroidism.