Abstract

In Iraq, there is no obvious considerable data regarding trimester-specific reference intervals of thyroid hormones despite documented multiple physiological hormonal changes during pregnancy. Thus, this study aimed to determine trimester-specific reference intervals for serum TSH, FT3, and FT4 and assess the incidence of thyroid function test misinterpretation and misdiagnosis among pregnant women using non-pregnant reference intervals. A thyroid function test was performed for 774 enrolled pregnant women. Reference intervals of TSH, FT3, and FT4 were ascertained in each pregnancy trimester. It was then compared to the adult non-pregnant values, and the incidence of misinterpretation was later calculated. TSH and FT4 reference interval values were lower than non-pregnant reference interval values. The application of non-pregnant women references values in pregnant women caused a serious misinterpretation and misdiagnosis in 66 (8.5%) pregnant women regarding TSH, and 34 (4.4%) pregnant women regarding FT4, while no misdiagnosis was noticed regarding FT3. The trimester-specific reference interval values of TSH, FT3, and FT4 in Iraqi pregnant women showed an obvious variation from non-pregnant reference intervals and the urgent advice to use the trimester-specific reference intervals to avoid misclassification of thyroid dysfunction during pregnancy.

References

1. Xing J, Yuan E, Li J, Zhang Y, Meng X, Zhang X, Rong S, et al. Trimester-and assay-specific thyroid reference intervals for pregnant women in China. Int J Endocr. 2016; 21: 3754213. 2. Silva JF, Ocarino NM, Serakides R. Thyroid hormones and female reproduction. Bio Rep. 2018; 99 (5): 907-21. 3. Hamasaeed PA, Hussain SK, Ashraf SM. Evaluation of Thyroid stimulating hormone and thyroid hormone concentrations in females with hypothyroidism and hyperthyroidism. Rafidain J Sci. 2019; 28 (4): 1- 7. 4. Shinohara DR, da Silva Santos T, de Carvalho HC, Lopes LC, Günther LS, Aristides SM, Teixeira JJ, et al. Pregnancy complications associated with maternal hypothyroidism: a systematic review. Obstet Gynecol Surv. 2018; 73 (4): 219-30. 5. Tudosa R, Vartej P, Horhoianu I, Ghica C, Mateescu S, Dumitrache I. Maternal and fetal complications of the hypothyroidism-related pregnancy. Maedica. 2010; 5 (2): 116. 6. Wang S, Teng WP, Li JX, Wang WW, Shan ZY. Effects of maternal subclinical hypothyroidism on obstetrical outcomes during early pregnancy. J Endocrinol Invest. 2012; 35 (3): 322-5. 7. Razaq S, Al-Lehibi KI. Evaluation to the level of some inflammatory markers in hypothyroid insulin resistant patients. Baghdad Sci J. 2014; 11 (1): 33-4. 8. Anagnostis P, Lefkou E, Goulis DG. Re: "guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum" by Alexander et al.( Thyroid 2017; 27: 315–89). Thyroid. 2017 Sep 1; 27 (9): 1209-10. 9. Lee YJ, Kim CH, Kwack JY, Ahn JW, Kim SH, Chae HD, et al. Subclinical hypothyroidism diagnosed by thyrotropin-releasing hormone stimulation test in infertile women with basal thyroid-stimulating hormone levels of 2.5 to 5.0 mIU/L. Obstet Gynecol Sci. 2014; 57 (6): 507-12. 10. Moon HW, Chung HJ, Park CM, Hur M, Yun YM. Establishment of trimester-specific reference intervals for thyroid hormones in Korean pregnant women. Anns Lab Med. 2015; 35 (2): 198-204. 11. Mehran L, Tohidi M, Sarvghadi F, Delshad H, Amouzegar A, Soldin OP, et al. Management of thyroid peroxidase antibody euthyroid women in pregnancy: comparison of the american thyroid association and the endocrine society guidelines. J Thyroid Res. 2013; 2013: 542692. 12. Vissenberg R, Van den Boogaard E, Van Wely M, Van der Post JA, Fliers E, Bisschop PH, et al. Treatment of thyroid disorders before conception and in early pregnancy: a systematic review. Hum Reprod Update. 2012; 18 (4): 360-73. 13. Dal Lago A, Galanti F, Miriello D, Marcoccia A, Massimiani M, Campagnolo L, et al. Positive impact of levothyroxine treatment on pregnancy outcome in euthyroid women with thyroid autoimmunity affected by recurrent miscarriage. J Clin Med. 2021; 10 (10): 2105. 14. Bashi FNK, Mohammed HA. Outcomes of Pregnancy in Euthyroid Women with Positive Thyroid Peroxidase Antibodies. Egyptian J Chemist. 2021; 64 (11): 5-6. 15. Godines-Enriquez MS, Miranda-Velásquez S, Enríquez-Pérez MM, Arce-Sánchez L, Martínez-Cruz N, Flores-Robles CM, et al. Prevalence of thyroid autoimmunity in women with recurrent pregnancy loss. Medicina. 2021; 57 (2): 96. 16. Medici M, Korevaar TI, Visser WE, Visser TJ, Peeters RP. Thyroid function in pregnancy: what is normal?. Clin Chemist. 2015; 61 (5): 704-13. 17. Anandappa S, Joshi M, Polanski L, Carroll PV. Thyroid disorders in subfertility and early pregnancy. Therapeutic Advances in Endocrinology and Metabolism. 2020; 11: 2042018820945855. 18. Moleti M, Trimarchi F, Vermiglio F. Thyroid physiology in pregnancy. Endocr Pract. 2014; 20 (6): 589-96. 19. Khadilkar S. Thyroid-stimulating hormone values in pregnancy: cutoff controversy continues?. J Obs and Gyn of India. 2019; 69 (5): 389– 94. 20. Jebasingh FK, Salam R, Meetei TL, Singh PT, Singh NN, Prasad L. Reference intervals in evaluation of maternal thyroid function of Manipuri women. Indian Journal of Endocrinology and Metabolism. 2016; 20 (2): 167. 21. Abalovich M, Vázquez A, Alcaraz G, Kitaigrodsky A, Szuman G, Calabrese C, Astarita G, et al. Adequate levothyroxine doses for the treatment of hypothyroidism newly discovered during pregnancy. Thyroid. 2013; 23 (11): 1479-83. 22. Murillo-Llorente, MT, Fajardo-Montañana C, & Pérez-Bermejo M. Reference Values of Thyroid Hormones During the First Trimester of Pregnancy in Valencian Community (Spain) and Their Relationship with Iodine Intake. Nutrients. 2020; 12 (5): 1433. 23. Lazarus J, Brown RS, Daumerie C, Hubalewska-Dydejczyk A, Negro R, Vaidya, B. 2014 European thyroid association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. Eur thyroid j. 2014; 3 (2): 76-94. 24. Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, et al. 2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. 2017; 27 (3): 315-89. 25. Li C, Shan Z, Mao J, Wang W, Xie X, Zhou W, Li C, et al. Assessment of thyroid function during first-trimester pregnancy: what is the rational upper limit of serum TSH during the first trimester in Chinese pregnant women?. J Clin Endocrinol Metab. 2014; 99 (1): 73-9. 26. Mumtaz A, Sadiq F, Zaki S, Batool H, Ibrahim M, Khurram M, et al. Trimester-specific reference ranges for thyroid hormones of pregnant females at tertiary care hospitals in Lahore, Pakistan. BMC Pregnancy and Childbirth. 2021; 21: 717. 27. Daniel WW. Biostatistics: a foundation for analysis in health science. 10th ed. New York: John Wiley and Sons Inc; 2013. 28. Delitala AP, Capobianco G, Cherchi PL, Dessole S, Delitala G. Thyroid function and thyroid disorders during pregnancy: a review and care pathway. Archives of gynecology and obstetrics. 2019; 299 (2): 327–38. 29. Park CE. Evaluation of pregnancy and thyroid function. The Korean Journal of Clinical Laboratory Science. Korean J Clin Lab Sci. 2018; 50: 1-10. 30. McNeil AR, Stanford PE. Reporting thyroid function tests in pregnancy. Clin Biochem Rev. 2015; 36 (4): 109–26. 31. Vanderpump MPJ. The epidemiology of thyroid disease. The thyroid and its diseases. 2019; 77-85. 32. Zhang J, Li W, Chen QB, Liu LY, Zhang W, Liu MY, Wang YT, Li WY, Zeng LZ. Establishment of trimester-specific thyroid stimulating hormone and free thyroxine reference interval in pregnant Chinese women using the Beckman Coulter UniCel™ DxI 600. Clin Chem Lab Med. 2015; 53 (9): 1409-14. 33. Yalamanchi S, Cooper DS. Thyroid disorders in pregnancy. Curr Opin Obstet Gynecol. 2015; 27 (6): 406-15. 34. Almomin AM, Mansour AA, Sharief M. Trimester-specific reference intervals of tyroid function testing in pregnant women from Basrah, Iraq using electrochemiluminescent immunoassay. Diseases. 2016; 4 (2): 20. 35. Naif M, Allawi H. Trimester-Specific Thyrotropin Hormone Reference Levels in Mosul City, Iraq. Egyptian Journal of Chemistry. 2021; 64 (12): 7631-6. 36. Sheriba NA, Ibrahim NA, Mohamed NR. Hegab AM. Assessment of normal range of thyroid function tests in healthy Egyptian pregnant women. Thyroid Res Pract. 2018; 15 (2): 70- 4. 37. Khalil AB, Salih B, Chinengo O, Bardiès M, Turner A, Wareth LAO. Trimester specific reference ranges for serum TSH and Free T4 among United Arab Emirates pregnant women. Pract Lab Med. 2018; 12: e00098. 38. Alhamd AKJ, Mohammed HQ, Al-dhahiry JKS. Evaluation of thyroid function at different stages of pregnancy in Iraqi women. AJPS. 2013; 13 (2): 139-46. 39. Yang X, Meng Y, Zhang Y, Zhang C, Guo F, Yang S, Ding R, Fan JX. Thyroid function reference ranges during pregnancy in a large Chinese population and comparison with current guidelines. Chin Med J. 2019; 132 (05): 505-11. 40. Abel MH, Korevaar TI, Erlund I, Villanger GD, Caspersen IH, Arohonka P, Alexander J, Meltzer HM, Brantsæter AL. Iodine intake is associated with thyroid function in mild to moderately iodine deficient pregnant women. Thyroid. 2018; 28 (10): 1359-71. 41. Padmakumar A, Dias LA, Sharma N. Thyroid function tests in euthyroid pregnant and non-pregnant women. J Cardio Diabetes Metab Disord. 2021; 1 (2): 41-5. 42. Mehran L, Amouzegar A, Delshad H, Askari S, Hedayati M, Amirshekari G, Azizi F. Trimester-specific reference ranges for thyroid hormones in Iranian pregnant women. J Thyroid Res. 2013; 2013: 651617. 43. Azizi F, Mehran L, Amouzegar A, Delshad H, Tohidi M, Askari S, Hedayati M. Establishment of the trimester-specific reference range for free thyroxine index. Thyroid. 2013; 23 (3): 354-9. 44. Sekhri T, Juhi JA, Wilfred R, Kanwar RS, Sethi J, Bhadra K, Nair S Singh S. Trimester specific reference intervals for thyroid function tests in normal Indian pregnant women. Indian J Endocrinol Metab. 2016; 20 (1): 101. 45. Hernández JM, Soldevila B, Velasco I, Moreno-Flores F, Ferrer L, Pérez-Montes de Oca A, Santillán C, Muñoz C, Ballesta S, Canal C, Puig-Domingo M. Reference intervals of thyroid function tests assessed by immunoassay and mass spectrometry in healthy pregnant women living in Catalonia. J Clin Med. 2021; 10 (11): 2444. 46. Yan YQ, Dong ZL, Dong L, Wang FR, Yang XM, Jin XY, et al. Trimester-and method-specific reference intervals for thyroid tests in pregnant Chinese women: methodology, euthyroid definition and iodine status can influence the setting of reference intervals. Clin endocrinol. 2011; 74 (2): 262-9. 47. Kurioka H, Takahashi K, Miyazaki K. Maternal thyroid function during pregnancy and puerperal period. Endocr J. 2005; 52 (5): 587-91. 48. Baloch Z, Carayon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, et al. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid. 2003; 13 (1): 3-126.

Share

COinS