ETA2022 Oral Presentations Oral Session 5: Autoimmunity (5 abstracts)
Cut-offs for thyroid peroxidase and thyroglobulin antibodies in early pregnancy are not similar and may differ from non-pregnant individuals: evidence from 10,905 danish pregnant women
Stine Linding Andersen 1 , Niels Henrik Bruun 2 , Peter Astrup Christensen 3 , Simon Lykkeboe 3 , Aase Handberg 3 , Annebirthe Bo Hansen 3 , Maja Berg Hjelm 3 , Louise Knøsgaard 3 , Nanna Maria Uldall Torp 3 , Allan Carlé 4 , Jesper Scott Karmisholt 4 , Inge Bülow Pedersen 4 , Peter Vestergaard 4 & Stig Andersen 5
1Aalborg University Hospital, Aalborg University, Department of Clinical Biochemistry, Aalborg, Denmark; 2Unit of Clinical Biostatistics, Aalborg University Hospital, Denmark; 3Department of Clinical Biochemistry, Aalborg University Hospital, Denmark; 4Department of Endocrinology, Aalborg University Hospital, Denmark; 5Department of Geriatrics, Aalborg University Hospital, Denmark
Objectives: Thyroid disease in women of reproductive age is predominantly of autoimmune origin, and thyroid peroxidase antibodies (TPO-Ab) as well as thyroglobulin antibodies (Tg-Ab) are key markers of autoimmune hypothyroidism. Adding to this, much focus in pregnancy is on euthyroid women who are positive for thyroid autoantibodies. The observational findings are diverse, and evidence to substantiate the applied cut-offs for definition of thyroid autoantibody-positivity in early pregnant women is warranted.
Methods: The North Denmark Region Pregnancy Cohort, 2011-2015, includes biochemical assessment of thyroid function, TPO-Ab, and Tg-Ab (ADVIA Centaur XPT, Siemens Healthineers) in stored blood samples from 14,030 early pregnant women. Antibody cut-offs recommended by the manufacturer (non-pregnant) were 60 U/ml for both TPO-Ab and Tg-Ab. Within the cohort, euthyroid singleton pregnant women with no history of thyroid disease were identified for establishment of antibody cut-offs (reference cohort). TPO-Ab and Tg-Ab showed skewed distributions with 50.7% and 66.4% of the values below the detection limits of 28 U/ml and 15 U/ml, respectively. Thus, antibody cut-offs (95% percentiles) were established by Regression on Order Statistics.
Results: Altogether 10,905 pregnant women were included in the reference cohort, and the established cut-offs for thyroid autoantibodies within the cohort were 59 U/ml (TPO-Ab) and 33 U/ml (Tg-Ab). The cut-offs were then applied in the full cohort of 14,030 pregnant women showing that 1,545 women (11.0%) were TPO-Ab positive, 1,870 (13.3%) were Tg-Ab positive, and 1,079 (7.7%) were TPO-Ab and Tg-Ab positive. Considering maternal thyroid function by antibody-status (Table), TSH was higher and free T4 lower among antibody-positive as compared to antibody-negative women with each of the applied cut-offs.
| Antibody-positive | Antibody-negative | |||||
| TPO-Ab > 59 U/ml | TPO-Ab ≤ 59 U/ml | |||||
| n | Median | 95% CI | n | Median | 95% CI | |
| TSH (mIU/l) | 1,545 | 1.73 | 1.67-1.79 | 12,485 | 1.07 | 1.05-1.09 |
| Free T4 (pmol/l) | 1,545 | 15.61 | 15.46-15.71 | 12,485 | 16.03 | 15.99-16.07 |
| Tg-Ab > 33 U/ml | Tg-Ab ≤ 33 U/ml | |||||
| n | Median | 95% CI | n | Median | 95% CI | |
| TSH (mIU/l) | 1,870 | 1.64 | 1.58-1.69 | 12,160 | 1.06 | 1.05-1.08 |
| Free T4 (pmol/l) | 1,870 | 15.57 | 15.46-15.67 | 12,160 | 16.04 | 16.00-16.09 |
Conclusions: In a large cohort of Danish pregnant women, cut-offs for TPO-Ab and Tg-Ab in early pregnancy were established while considering the skewed distributions. The established cut-offs were not similar for TPO-Ab and Tg-Ab, and the cut-off for Tg-Ab was lower than recommended in non-pregnant individuals. The findings are important regarding classification of exposure in pregnancy outcome studies and specifically regarding the assessment of thyroid autoimmunity per se.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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