Endocrine Abstracts

Objective: Physiological alterations challenge the assessment of maternal thyroid function in pregnancy. It remains uncertain how the reference ranges vary by week of pregnancy, and how the classification of maternal thyroid disease vary by analytical method and type of thyroid function test.

Method: Consecutively collectedserum samples from 6.282 pregnant women in the North Denmark Region, 2011–2013, were used for the measurement of thyrotropin (TSH), total and free thyroxine (T4), total and free triiodothyronine (T3), and T-uptake using ‘Method A’ (Cobas 8000, Roche Diagnostics). TSH and free T4 were also previously measured using ‘Method B’ (ADVIA Centaur XP, Siemens Healthineers). Pregnancy week- and method-specific reference ranges (2.5 and 97.5 percentiles) were established after the exclusion of multiple births, women who were positive for thyroid peroxidase antibodies (TPO-Ab) and/or thyroglobulin antibodies (Tg-Ab), had thyroid or other autoimmune diseases or used thyroid interfering medication. Box-Cox transformation and Tukey’s fences were used for detection and exclusion of outliers. The established reference ranges were used to classify maternal thyroid function, and classifications were compared by analytical method and type of thyroid function test. Roche Diagnostics supported the study by offering a discount for the thyroid function tests performed.

Results: The reference ranges for TSH showed a gradual decrease during pregnancy week 4–14, a gradual increase was observed for total T4, total T3, and T-uptake, whereas free T4 and free T3 showed less variation. Altogether 689 of the pregnant women had TSH outside the reference range with either method A or B, and 541 of these (78.5%) had an abnormal TSH result with both methods. For free T4, 707 of the pregnant women had a test result outside the reference range with either method A or B, and 216 (30.6%) with both methods. When both TSH and free T4 were used for classification of maternal thyroid function, Method A classified 935 with abnormal thyroid function, Method B a total of 903, and the methods agreed on 554 individuals. When TSH and total T4 were used, 947 were classified with abnormal thyroid function, and classifications by TSH in combination with either total T4 or free T4 agreed on 584 individuals.

Conclusion: Even when pregnancy week- and method-specific reference ranges were established, the classification of maternal thyroid disease varied considerably by analytical method and across the different clinical available thyroid function tests. The findings raise a concern about misclassification, particularly for the use of free thyroid hormones.